http://togogenome.org/gene/11082:WNVgp1                                                                                  ^@                                                                                  http://purl.uniprot.org/uniprot/P06935                                                                                  ^@                                                                                  Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit                                                                                  ^@                                                                                  Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.|||Binds to host cell surface receptor and mediates fusion between viral and cellular membranes (PubMed:15367621). Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM (By similarity). They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E (By similarity). The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers (By similarity). prM-E cleavage is inefficient, and many virions are only partially matured (By similarity). These uncleaved prM would play a role in immune evasion (By similarity).|||Cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. This cleavage is incomplete as up to 30% of viral particles still carry uncleaved prM.|||Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response.|||Contains a PDZ-binding motif that binds to several PDZ-containing cellular proteins. These interactions seem necessary for an optimal viral replication.|||Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). NS3 supports the separation of RNA daughter and template strands during viral replication. The helicase part is involved in the inhibition of phosphorylation of host STAT1, and thereby inhibition of host type-I IFN signaling (By similarity). In addition, NS3 assists the initiation of replication by unwinding the RNA secondary structure in the 3' non-translated region (NTR). Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity).|||Forms a heterodimer with NS2B (By similarity). Interacts with NS4B (By similarity). Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity (By similarity).|||Forms a heterodimer with serine protease NS3 (By similarity). May form homooligomers (By similarity).|||Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi (By similarity).|||Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.|||Homodimer (By similarity). Interacts (via N-terminus) with host EXOC1 (via C-terminus) (PubMed:19889084, PubMed:23522008); this interaction results in EXOC1 degradation through the proteasome degradation pathway (PubMed:23522008). Interacts with host DDX56; this interaction plays an important role in genomic RNA encapsidation (By similarity).|||Homodimer (By similarity). Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation (By similarity). Interacts with host PAF1 complex (PubMed:30550790).|||Homodimer; Homohexamer when secreted (By similarity). Interacts with envelope protein E (By similarity). NS1 interacts with NS4B (By similarity). Interacts with host complement protein CFH; this interaction leads to the degradation of C3 (By similarity).|||Homodimer; in the endoplasmic reticulum and Golgi (By similarity).|||Host cytoplasm|||Host endoplasmic reticulum membrane|||Host nucleus|||In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type methyltransferase family.|||Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment.|||Inhibits RNA silencing by interfering with host Dicer.|||Interacts (via N-terminus) with serine protease NS3.|||Interacts with Serine protease/Helicase NS3 (By similarity). Interacts with NS1 (By similarity).|||Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).|||May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.|||N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells.|||Not N-glycosylated.|||Phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization.|||Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle (By similarity). During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins (By similarity). Can migrate to the cell nucleus where it modulates host functions (By similarity). Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway (PubMed:23522008).|||Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.|||Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding.|||Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm (PubMed:17267492). NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions (PubMed:17267492). Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway (By similarity). Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).|||Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).|||Secreted|||Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, whereas cleavages in the cytoplasmic side are performed by serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.|||The transmembrane domains contain an endoplasmic reticulum retention signal.|||Virion|||Virion membrane|||host perinuclear region