847 SARS-CoV-2 Spike - human ACE2 receptor complex SARS-CoV-2 Spike - human ACE2-SLC6A19 complex SARS-CoV Spike - human ACE2 receptor complex 59 Bromhexine Chloroquine Hydroxychloroquine N-(2-Aminoethyl)-1-aziridineethanamine SPP1148 the neurotransmitter:sodium symporter (nss) family the angiotensin-converting enzyme 2 (ace2) family 115 N-Linked glycans (3 sites), 1 O-Fuc glycan, 14 O-Linked glycans (1 site) 8 sites, 161 glycans 19 sites, 218 N-linked glycans (8 sites), 35 O-linked glycans (11 sites) 2 sequenced antibodies 1302 antibodies from 46 providers human ACE2 Tissue enhanced (gallbladder, intestine, kidney) gene Eukaryota 2681 2681 Metabolism of Angiotensinogen to Angiotensins Attachment and Entry Potential therapeutics for SARS Attachment and Entry Induction of Cell-Cell Fusion 35 hits in 793 CRISPR screens human Tchem protein Expressed in ileal mucosa and 94 other tissues baseline and differential HS M2_ACE Collectrin_dom Peptidase_M2 ANGIOTENSIN-CONVERTING ENZYME ANGIOTENSIN-CONVERTING ENZYME 2 Collectrin Peptidase_M2 PEPDIPTASEA Metalloproteases ('zincins'), catalytic domain COLLECTRIN_LIKE PEPTIDASE_M2 ZINC_PROTEASE Angiotensin-converting enzyme 2 3.4.17.23 Angiotensin-converting enzyme homolog ACEH Angiotensin-converting enzyme-related carboxypeptidase ACE-related carboxypeptidase 3.4.17.- Metalloprotease MPROT15 Processed angiotensin-converting enzyme 2 ACE2 UNQ868/PRO1885 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 (PubMed:27217402). 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 (PubMed:10969042, PubMed:10924499, PubMed:11815627, PubMed:19021774, PubMed:14504186). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity (PubMed:18424768, PubMed:19185582). (Microbial infection) Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63. Non-functional as a carboxypeptidase. (Microbial infection) Non-functional as a receptor for human coronavirus SARS-CoV-2. Binds 1 zinc ion per subunit. Binds 1 Cl(-) ion per subunit. Regulated by chloride and fluoride, but not bromide (PubMed:11815627). Chloride increases angiotensin I and decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by the ACE inhibitors lisinopril, captopril and enalaprilat (PubMed:10969042, PubMed:10924499). Highly potent and selective in vitro ACE2 inhibitors were identified (PubMed:12358520). kcat is 0.034 sec(-1) with angiotensin I as substrate. kcat is 3.5 sec(-1) with angiotensin II as substrate. kcat is 13 sec(-1) with apelin-13 as substrate. kcat is 62 sec(-1) with [des-Arg(9)]-bradykinin as substrate. kcat is 26 sec(-1) with Lys-[des-Arg(9)]-bradykinin as substrate. kcat is 6.8 sec(-1) with beta-casomorphin as substrate. kcat is 16 sec(-1) with dynorphin A-(1-13) as substrate. kcat is 57 sec(-1) with neurotensin-(1-8) as substrate (PubMed:11815627). kcat is 19.1 sec(-1) with [Pyr1]apelin-13 as substrate. kcat is 7.7 sec(-1) with apelin-17 as substrate (PubMed:27217402). 6.9 uM for angiotensin I 2 uM for angiotensin II 6.8 uM for apelin-13 290 uM for [des-Arg(9)]-bradykinin 130 uM for Lys-[des-Arg(9)]-bradykinin 31 uM for beta-casomorphin 5.5 uM for dynorphin A-(1-13) 300 uM for neurotensin-(1-8) 58.6 uM for angiotensin II 12 uM for [Pyr1]apelin-13 19 uM for apelin-17 28.7 nmol/min/mg enzyme with angiotensin II as substrate Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9. Homodimer (PubMed:32132184). Interacts with the catalytically active form of TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (By similarity). Interacts with ITGA5:ITGB1 (PubMed:15276642, PubMed:33102950). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (PubMed:33436498). Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (PubMed:34189428). (Microbial infection) Interacts with SARS coronavirus/SARS-CoV spike protein. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein (via RBD domain). (Microbial infection) Interacts with human coronavirus NL63 spike protein. (Microbial infection) Interacts with human coronavirus NL63/HCoV-NL63 spike glycoprotein. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein; the interaction is increased by AVP/Arg-vasopressin with which they may form a complex. Detected in both cell membrane and cytoplasm in neurons. Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells (at protein level) (PubMed:15141377). Expressed in enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level) (PubMed:15141377). Expressed in the renal proximal tubule and the small intestine (at protein level) (PubMed:18424768). Expressed in heart, kidney, testis, and gastrointestinal system (at protein level) (PubMed:10969042, PubMed:10924499, PubMed:15231706, PubMed:12459472, PubMed:15671045, PubMed:32715618, PubMed:32170560). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level) (PubMed:32425701, PubMed:15141377, PubMed:32715618, PubMed:32170560, PubMed:33432184). Expressed in nasal epithelial cells (at protein level) (PubMed:33432184, PubMed:32333915). Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells (PubMed:32413319, PubMed:32327758, PubMed:32358202). Coexpressed with TMPRSS4 within mature enterocytes (PubMed:32404436). Expressed in nasal and bronchial epithelial cells (at protein level). Up-regulated in failing heart (PubMed:14504186, PubMed:15151696, PubMed:15671045). Expression is induced by IFNA and IFNG (PubMed:32413319, PubMed:32425701). Exposure to cigarette smoke increases expression in lungs (PubMed:32425701). Expression is decreased in nasal and bronchial epithelium of individuals with allergy after allergen challenge (PubMed:32333915). IL13 stimulation decreases expression in nasal and bronchial epithelium (PubMed:32333915). Not induced by interferons such as IFNA, IFNB and IFNG. Expression is induced by interferons such as IFNA, IFNB and IFNG. It seems that isoform 2 is an interferon-stimulated gene (ISG) but not isoform 1. (Microbial infection) In airway epithelial cells, expression is increased upon influenza A virus infection (PubMed:32413319). (Microbial infection) In airway epithelial cells, expression is induced by viruses such rhinoviruses and influenza virus. (Microbial infection) Induced by human coronavirus SARS-CoV-2. The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin. 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. N-glycosylation on Asn-90 may limit SARS infectivity. Proteolytic cleavage by ADAM17 generates a secreted form (PubMed:15983030, PubMed:33713620). Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1. Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains. An engeneered stable, dimeric and secreted receptor with combined mutations that increase the affinity for human coronavirus SARS-CoV-2 spike protein shows potent SARS-CoV and SARS-CoV-2 neutralization in vitro. Belongs to the peptidase M2 family. 1 17 Angiotensin-converting enzyme 2 90745 18 805 Processed angiotensin-converting enzyme 2 80106 708 Extracellular 740 Helical 741 761 Cytoplasmic 762 Peptidase M2 19 607 Collectrin-like 614 Interaction with SARS-CoV spike glycoprotein 30 41 Interaction with SARS-CoV spike glycoprotein 82 84 Interaction with SARS-CoV spike glycoprotein 353 357 Essential for cleavage by ADAM17 652 659 Essential for cleavage by TMPRSS11D and TMPRSS2 697 716 Disordered 772 LIR 778 786 SH2-binding 781 785 Endocytic sorting signal 784 PTB 792 795 PDZ-binding 803 Polar residues Proton acceptor 375 Proton donor 505 169 273 345 346 374 378 402 477 481 515 Phosphotyrosine Phosphoserine 783 N-linked (GlcNAc...) asparagine 53 N-linked (GlcNAc...) asparagine 90 N-linked (GlcNAc...) asparagine 103 N-linked (GlcNAc...) asparagine 322 N-linked (GlcNAc...) asparagine 432 N-linked (GlcNAc...) asparagine 546 N-linked (GlcNAc...) asparagine 690 133 141 344 361 530 542 In isoform 2. MREAGWDKGG 356 R 26 V 468 S 638 D 720 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. P Slightly inhibits interaction with SARS-CoV spike glycoprotein. KAE 24 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. T Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. V 25 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-330 and L-386. Y 27 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. F 29 Abolishes interaction with SARS-CoV spike glycoprotein. D 31 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. Y Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. D 33 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. A 34 No effect on interaction with SARS-CoV spike glycoprotein. A 37 No effect on interaction with SARS-CoV spike glycoprotein. A 38 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. R 39 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. D 40 Strongly inhibits interaction with SARS-CoV spike glycoprotein. A Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. R Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. L 42 Slightly inhibits interaction with SARS-CoV spike glycoprotein. D 68 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. V 69 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. Y 72 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. K 75 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. T 76 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. T 79 Inhibits interaction with SARS-CoV spike glycoprotein. NFS Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. P 89 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. Q Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. P 91 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. Q 92 No effect on interaction with SARS-CoV spike glycoprotein. P 110 No effect on interaction with SARS-CoV spike glycoprotein. SM 135 136 No effect on interaction with SARS-CoV spike glycoprotein. R 160 About 95% loss of angiotensin I cleavage. Q No effect on interaction with SARS-CoV spike glycoprotein. D 192 No effect on interaction with SARS-CoV spike glycoprotein. D 219 No effect on interaction with SARS-CoV spike glycoprotein. Q 239 About 95% loss of angiotensin I cleavage. Q 271 Complete loss of enzyme activity. Does not affect amino acid transport activity of SLC6A19. Q No effect on interaction with SARS-CoV spike glycoprotein. D 309 No effect on interaction with SARS-CoV spike glycoprotein. A 312 No effect on interaction with SARS-CoV spike glycoprotein. A 324 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. P Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. P 325 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and L-386. Y 330 No effect on interaction with SARS-CoV spike glycoprotein. DDR 338 340 Complete loss of enzyme activity. A No effect on interaction with SARS-CoV spike glycoprotein. A 350 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. F 351 Abolishes interaction with SARS-CoV spike glycoprotein. H A D Strongly inhibits interaction with SARS-CoV spike glycoprotein. A 355 Strongly inhibits interaction with SARS-CoV spike glycoprotein. A No effect on interaction with SARS-CoV spike glycoprotein. K A 359 Slightly inhibits interaction with SARS-CoV spike glycoprotein. A 383 Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and Y-330. L 386 Slightly inhibits interaction with SARS-CoV spike glycoprotein. A 389 Increases very slightly the interaction with RBD domain of SARS-CoV-2 spike protein. D Slightly inhibits interaction with SARS-CoV spike glycoprotein. A 393 Increases very slightly the interaction with RBD domain of SARS-CoV-2 spike protein. K Slightly inhibits interaction with SARS-CoV spike glycoprotein. PSN 425 427 No effect on interaction with SARS-CoV spike glycoprotein. QDK 465 467 About 80% loss of angiotensin I cleavage. Q Complete loss of enzyme activity. A About 50% loss of angiotensin I cleavage but two-fold greater activity with angiotensin II. Q 514 Increases very slightly the interaction with RBD domain of SARS-CoV-2 spike protein. G 518 Slightly inhibits interaction with SARS-CoV spike glycoprotein. S 559 No effect on interaction with SARS-CoV spike glycoprotein. T 603 Loss of interaction with NHERF1. AAAA 802 H D 508 R 631 23 52 56 77 78 85 87 100 104 107 129 131 134 137 143 144 146 148 154 158 171 173 193 196 198 199 204 205 207 213 215 220 251 253 255 258 260 264 266 267 276 278 279 282 284 287 294 297 298 300 304 316 317 319 327 337 339 347 352 366 384 385 387 390 392 396 399 400 413 415 420 422 426 446 449 466 470 472 473 483 486 488 494 496 499 502 504 507 531 532 534 539 541 548 558 562 566 574 575 578 582 598 600 602 609 612 615 618 622 624 627 629 637 657 667 669 670 673 677 686 694 706 715 719 724 765 substrate catalytic false 8 false 2 false 5 false 2 false 3 false 3 false 4 false 2 false 6 false 4 false 19 false 5 false 2 false 3 false 2 false 2 false 4 false 7 false 2 false 3 false 4 true 4 true 2 true 4 true 4 true 254 true 2 true 57 true 3 true 2 true 9 ACE2 AGT AGT AP2M1 APP CLEC4M DEFA5 GRM2 HSPA5 ITGB1 KDM1A KNG1 NTS PDZK1 SFTPD SHANK1 SLC6A19 SLC9A3R1 SNX27 TMPRSS2 VIM Kpna2 S S S S S S S S S 2005-08-02 2 true 92463 906dc56d5c9c5513eef859ee82e80267 1 long MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENPYASIDISKGENNPGFQNTDDVQTSF 2 delta dACE2 short MREAGWDKGGRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENPYASIDISKGENNPGFQNTDDVQTSF true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true true 2007-05-29 2023-06-28 148 B3GN5_HUMAN Togayachi A. Akashima T. Ookubo R. Kudo T. Nishihara S. Iwasaki H. Natsume A. Mio H. Inokuchi J. Irimura T. Sasaki K. Narimatsu H. doi:10.1074/jbc.m011369200 2001 J. Biol. Chem. 276 22032-22040 NUCLEOTIDE SEQUENCE [MRNA] CATALYTIC ACTIVITY TISSUE SPECIFICITY INDUCTION FUNCTION Henion T.R. Zhou D. Wolfer D.P. Jungalwala F.B. Hennet T. doi:10.1074/jbc.m102979200 2001 J. Biol. Chem. 276 30261-30269 NUCLEOTIDE SEQUENCE [MRNA] CATALYTIC ACTIVITY FUNCTION Bennett E.P. 2000-12 EMBL/GenBank/DDBJ NUCLEOTIDE SEQUENCE [MRNA] Totoki Y. Toyoda A. Takeda T. Sakaki Y. Tanaka A. Yokoyama S. Ohara O. Nagase T. Kikuno R.F. 2005-03 EMBL/GenBank/DDBJ NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] Brain Mural R.J. Istrail S. Sutton G.G. Florea L. Halpern A.L. Mobarry C.M. Lippert R. Walenz B. Shatkay H. Dew I. Miller J.R. Flanigan M.J. Edwards N.J. Bolanos R. Fasulo D. Halldorsson B.V. Hannenhalli S. Turner R. Yooseph S. Lu F. Nusskern D.R. Shue B.C. Zheng X.H. Zhong F. Delcher A.L. Huson D.H. Kravitz S.A. Mouchard L. Reinert K. Remington K.A. Clark A.G. Waterman M.S. Eichler E.E. Adams M.D. Hunkapiller M.W. Myers E.W. Venter J.C. 2005-09 EMBL/GenBank/DDBJ NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] The MGC Project Team doi:10.1101/gr.2596504 2004 Genome Res. 14 2121-2127 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] Functional Glycomics Gateway - GTase; Beta1,3-N-acetylglucosaminyltransferase 5 Frameshift. 5 2 Glycosyltransferase Family 31 1 site, No reported glycans 1 site