ID POLG_WNV Reviewed; 3430 AA. AC P06935; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 24-OCT-2003, sequence version 2. DT 08-MAY-2019, entry version 184. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Peptide 2k; DE Contains: DE RecName: Full=Capsid protein C; DE AltName: Full=Core protein; DE Contains: DE RecName: Full=Protein prM; DE Contains: DE RecName: Full=Peptide pr; DE Contains: DE RecName: Full=Small envelope protein M; DE AltName: Full=Matrix protein; DE Contains: DE RecName: Full=Envelope protein E; DE Contains: DE RecName: Full=Non-structural protein 1; DE Short=NS1; DE Contains: DE RecName: Full=Non-structural protein 2A; DE Short=NS2A; DE Contains: DE RecName: Full=Serine protease subunit NS2B; DE AltName: Full=Flavivirin protease NS2B regulatory subunit; DE AltName: Full=Non-structural protein 2B; DE Contains: DE RecName: Full=Serine protease NS3; DE EC=3.4.21.91; DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Q6P4}; DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9Q6P4}; DE AltName: Full=Flavivirin protease NS3 catalytic subunit; DE AltName: Full=Non-structural protein 3; DE Contains: DE RecName: Full=Non-structural protein 4A; DE Short=NS4A; DE Contains: DE RecName: Full=Non-structural protein 4B; DE Short=NS4B; DE Contains: DE RecName: Full=RNA-directed RNA polymerase NS5; DE EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924}; DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924}; DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539}; DE AltName: Full=NS5; OS West Nile virus (WNV). OC Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; OC Flaviviridae; Flavivirus. OX NCBI_TaxID=11082; OH NCBI_TaxID=7158; Aedes. OH NCBI_TaxID=34610; Amblyomma variegatum (Tropical bont tick). OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=53527; Culex. OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=34627; Hyalomma marginatum. OH NCBI_TaxID=308735; Mansonia uniformis. OH NCBI_TaxID=308737; Mimomyia. OH NCBI_TaxID=34630; Rhipicephalus. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3753811; DOI=10.1016/0042-6822(86)90082-6; RA Castle E., Leidner U., Nowak T., Wengler G., Wengler G.; RT "Primary structure of the West Nile flavivirus genome region coding RT for all nonstructural proteins."; RL Virology 149:10-26(1986). RN [2] RP SEQUENCE REVISION TO 1908; 2018-2036; 2242 AND 2859-2860. RX PubMed=11277701; DOI=10.1006/viro.2000.0795; RA Yamshchikov V.F., Wengler G., Perelygin A.A., Brinton M.A., RA Compans R.W.; RT "An infectious clone of the West Nile flavivirus."; RL Virology 281:294-304(2001). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-291. RX PubMed=2992152; DOI=10.1016/0042-6822(85)90156-4; RA Castle E., Nowak T., Leidner U., Wengler G., Wengler G.; RT "Sequence analysis of the viral core protein and the membrane- RT associated proteins V1 and NV2 of the flavivirus West Nile virus and RT of the genome sequence for these proteins."; RL Virology 145:227-236(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 255-854. RX PubMed=3855247; DOI=10.1016/0042-6822(85)90129-1; RA Wengler G., Castle E., Leidner U., Nowak T., Wengler G.; RT "Sequence analysis of the membrane protein V3 of the flavivirus West RT Nile virus and of its gene."; RL Virology 147:264-274(1985). RN [5] RP ABSENCE OF GLYCOSYLATION (ENVELOPE PROTEIN E). RX PubMed=2441520; RA Winkler G., Heinz F.X., Kunz C.; RT "Studies on the glycosylation of flavivirus E proteins and the role of RT carbohydrate in antigenic structure."; RL Virology 159:237-243(1987). RN [6] RP DISULFIDE BONDS (ENVELOPE PROTEIN E). RX PubMed=3811228; DOI=10.1016/0042-6822(87)90443-0; RA Nowak T., Wengler G.; RT "Analysis of disulfides present in the membrane proteins of the West RT Nile flavivirus."; RL Virology 156:127-137(1987). RN [7] RP FUNCTION (ENVELOPE PROTEIN E). RX PubMed=15367621; DOI=10.1128/JVI.78.19.10543-10555.2004; RA Chu J.J., Ng M.L.; RT "Infectious entry of West Nile virus occurs through a clathrin- RT mediated endocytic pathway."; RL J. Virol. 78:10543-10555(2004). RN [8] RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5). RC STRAIN=E101; RX PubMed=16699025; DOI=10.1128/JVI.01982-05; RA Uchil P.D., Kumar A.V., Satchidanandam V.; RT "Nuclear localization of flavivirus RNA synthesis in infected cells."; RL J. Virol. 80:5451-5464(2006). RN [9] RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF RP LYS-2586; ASP-2671; LYS-2707 AND GLU-2743. RX PubMed=17267492; DOI=10.1128/JVI.02704-06; RA Zhou Y., Ray D., Zhao Y., Dong H., Ren S., Li Z., Guo Y., RA Bernard K.A., Shi P.-Y., Li H.; RT "Structure and function of flavivirus NS5 methyltransferase."; RL J. Virol. 81:3891-3903(2007). RN [10] RP PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN). RX PubMed=17067286; DOI=10.1042/BJ20061136; RA Shiryaev S.A., Kozlov I.A., Ratnikov B.I., Smith J.W., Lebl M., RA Strongin A.Y.; RT "Cleavage preference distinguishes the two-component NS2B-NS3 serine RT proteinases of Dengue and West Nile viruses."; RL Biochem. J. 401:743-752(2007). RN [11] RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), AND SUBCELLULAR RP LOCATION (CAPSID PROTEIN C). RX PubMed=19889084; DOI=10.1111/j.1462-5822.2009.01407.x; RA Bhuvanakantham R., Li J., Tan T.T., Ng M.L.; RT "Human Sec3 protein is a novel transcriptional and translational RT repressor of flavivirus."; RL Cell. Microbiol. 12:453-472(2010). RN [12] RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), FUNCTION (CAPSID RP PROTEIN C), AND MUTAGENESIS OF VAL-14. RX PubMed=23522008; DOI=10.1111/cmi.12143; RA Bhuvanakantham R., Ng M.L.; RT "West Nile virus and dengue virus capsid protein negates the antiviral RT activity of human Sec3 protein through the proteasome pathway."; RL Cell. Microbiol. 15:1688-1706(2013). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 1420-1688. RX PubMed=16532006; DOI=10.1038/nsmb1073; RA Erbel P., Schiering N., D'Arcy A., Renatus M., Kroemer M., Lim S.P., RA Yin Z., Keller T.H., Vasudevan S.G., Hommel U.; RT "Structural basis for the activation of flaviviral NS3 proteases from RT dengue and West Nile virus."; RL Nat. Struct. Mol. Biol. 13:372-373(2006). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1419-1679. RX PubMed=17400917; DOI=10.1110/ps.072753207; RA Aleshin A.E., Shiryaev S.A., Strongin A.Y., Liddington R.C.; RT "Structural evidence for regulation and specificity of flaviviral RT proteases and evolution of the Flaviviridae fold."; RL Protein Sci. 16:795-806(2007). RN [15] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 291-688. RX PubMed=19713934; DOI=10.1038/emboj.2009.245; RA Cherrier M.V., Kaufmann B., Nybakken G.E., Lok S.M., Warren J.T., RA Chen B.R., Nelson C.A., Kostyuchenko V.A., Holdaway H.A., RA Chipman P.R., Kuhn R.J., Diamond M.S., Rossmann M.G., Fremont D.H.; RT "Structural basis for the preferential recognition of immature RT flaviviruses by a fusion-loop antibody."; RL EMBO J. 28:3269-3276(2009). CC -!- FUNCTION: Capsid protein C: Plays a role in virus budding by CC binding to the cell membrane and gathering the viral RNA into a CC nucleocapsid that forms the core of a mature virus particle (By CC similarity). During virus entry, may induce genome penetration CC into the host cytoplasm after hemifusion induced by the surface CC proteins (By similarity). Can migrate to the cell nucleus where it CC modulates host functions (By similarity). Overcomes the anti-viral CC effects of host EXOC1 by sequestering and degrading the latter CC through the proteasome degradation pathway (PubMed:23522008). CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:23522008}. CC -!- FUNCTION: Capsid protein C: Inhibits RNA silencing by interfering CC with host Dicer. {ECO:0000250|UniProtKB:P03314}. CC -!- FUNCTION: Peptide pr: Prevents premature fusion activity of CC envelope proteins in trans-Golgi by binding to envelope protein E CC at pH6.0. After virion release in extracellular space, gets CC dissociated from E dimers. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Protein prM: Acts as a chaperone for envelope protein E CC during intracellular virion assembly by masking and inactivating CC envelope protein E fusion peptide. prM is the only viral peptide CC matured by host furin in the trans-Golgi network probably to avoid CC catastrophic activation of the viral fusion activity in acidic CC Golgi compartment prior to virion release. prM-E cleavage is CC inefficient, and many virions are only partially matured. These CC uncleaved prM would play a role in immune evasion. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Small envelope protein M: May play a role in virus CC budding. Exerts cytotoxic effects by activating a mitochondrial CC apoptotic pathway through M ectodomain. May display a viroporin CC activity. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Envelope protein E: Binds to host cell surface receptor CC and mediates fusion between viral and cellular membranes CC (PubMed:15367621). Envelope protein is synthesized in the CC endoplasmic reticulum in the form of heterodimer with protein prM CC (By similarity). They play a role in virion budding in the ER, and CC the newly formed immature particle is covered with 60 spikes CC composed of heterodimer between precursor prM and envelope protein CC E (By similarity). The virion is transported to the Golgi CC apparatus where the low pH causes dissociation of PrM-E CC heterodimers and formation of E homodimers (By similarity). prM-E CC cleavage is inefficient, and many virions are only partially CC matured (By similarity). These uncleaved prM would play a role in CC immune evasion (By similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Non-structural protein 1: Involved in immune evasion, CC pathogenesis and viral replication. Once cleaved off the CC polyprotein, is targeted to three destinations: the viral CC replication cycle, the plasma membrane and the extracellular CC compartment. Essential for viral replication. Required for CC formation of the replication complex and recruitment of other non- CC structural proteins to the ER-derived membrane structures. CC Excreted as a hexameric lipoparticle that plays a role against CC host immune response. Antagonizing the complement function. Binds CC to the host macrophages and dendritic cells. Inhibits signal CC transduction originating from Toll-like receptor 3 (TLR3). CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: Non-structural protein 2A: Component of the viral RNA CC replication complex that functions in virion assembly and CC antagonizes the host alpha/beta interferon antiviral response. CC {ECO:0000250|UniProtKB:P14335}. CC -!- FUNCTION: Serine protease subunit NS2B: Required cofactor for the CC serine protease function of NS3. May have membrane-destabilizing CC activity and form viroporins (By similarity). CC {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE- CC ProRule:PRU00859}. CC -!- FUNCTION: Serine protease NS3: Displays three enzymatic CC activities: serine protease, NTPase and RNA helicase. NS3 serine CC protease, in association with NS2B, performs its autocleavage and CC cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, CC NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA CC helicase binds RNA and unwinds dsRNA in the 3' to 5' direction. CC {ECO:0000255|PROSITE-ProRule:PRU00860}. CC -!- FUNCTION: Non-structural protein 4A: Regulates the ATPase activity CC of the NS3 helicase activity. NS4A allows NS3 helicase to conserve CC energy during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: Peptide 2k: Functions as a signal peptide for NS4B and CC is required for the interferon antagonism activity of the latter. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Non-structural protein 4B: Induces the formation of ER- CC derived membrane vesicles where the viral replication takes place. CC Inhibits interferon (IFN)-induced host STAT1 phosphorylation and CC nuclear translocation, thereby preventing the establishment of CC cellular antiviral state by blocking the IFN-alpha/beta pathway. CC Inhibits STAT2 translocation in the nucleus after IFN-alpha CC treatment. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: RNA-directed RNA polymerase NS5: Replicates the viral CC (+) and (-) RNA genome, and performs the capping of genomes in the CC cytoplasm (PubMed:17267492). NS5 methylates viral RNA cap at CC guanine N-7 and ribose 2'-O positions (PubMed:17267492). Besides CC its role in RNA genome replication, also prevents the CC establishment of cellular antiviral state by blocking the CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway (By CC similarity). Inhibits host TYK2 and STAT2 phosphorylation, thereby CC preventing activation of JAK-STAT signaling pathway (By CC similarity). {ECO:0000250|UniProtKB:Q9Q6P4, CC ECO:0000269|PubMed:17267492}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which CC each of the Xaa can be either Arg or Lys and Yaa can be either CC Ser or Ala.; EC=3.4.21.91; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- CC COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, CC ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00539}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside CC 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; CC Evidence={ECO:0000250|UniProtKB:Q9Q6P4}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-(5'-triphosphoguanosine)-(purine-ribonucleotide)- CC [mRNA] + S-adenosyl-L-methionine = a 5'-(N(7)-methyl 5'- CC triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] + S- CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:11220, Rhea:RHEA- CC COMP:12925, Rhea:RHEA-COMP:13407, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:133968, ChEBI:CHEBI:136896; CC EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(purine- CC ribonucleotide)-[mRNA] + S-adenosyl-L-methionine = a 5'-(N(7)- CC methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine- CC ribonucleotide)-[mRNA] + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:19617, Rhea:RHEA-COMP:12925, Rhea:RHEA- CC COMP:12926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:133968, ChEBI:CHEBI:133969; CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; CC -!- SUBUNIT: Capsid protein C: Homodimer (By similarity). Interacts CC (via N-terminus) with host EXOC1 (via C-terminus) CC (PubMed:19889084, PubMed:23522008); this interaction results in CC EXOC1 degradation through the proteasome degradation pathway CC (PubMed:23522008). Protein prM: Forms heterodimers with envelope CC protein E in the endoplasmic reticulum and Golgi (By similarity). CC Envelope protein E: Homodimer; in the endoplasmic reticulum and CC Golgi (By similarity). Non-structural protein 1: Homodimer; CC Homohexamer when secreted (By similarity). NS1 interacts with NS4B CC (By similarity). Interacts with host complement protein CFH; this CC interaction leads to the degradation of C3 (By similarity). Non- CC structural protein 2A: Interacts (via N-terminus) with serine CC protease NS3 (By similarity). Non-structural protein 2B: Forms a CC heterodimer with serine protease NS3. May form homooligomers (By CC similarity). Serine protease NS3: Forms a heterodimer with NS2B. CC Interacts with NS4B. Interacts with unphosphorylated RNA-directed CC RNA polymerase NS5; this interaction stimulates RNA-directed RNA CC polymerase NS5 guanylyltransferase activity (By similarity). Non- CC structural protein 4B: Interacts with serine protease NS3. CC Interacts with NS1 (By similarity). RNA-directed RNA polymerase CC NS5: Homodimer (By similarity). Interacts with host STAT2; this CC interaction inhibits the phosphorylation of the latter, and, when CC all viral proteins are present (polyprotein), targets STAT2 for CC degradation (By similarity). {ECO:0000250|UniProtKB:P17763, CC ECO:0000269|PubMed:19889084, ECO:0000269|PubMed:23522008}. CC -!- INTERACTION: CC Q17NZ6:CTLMA15 (xeno); NbExp=5; IntAct=EBI-2912469, EBI-2912457; CC P05106:ITGB3 (xeno); NbExp=4; IntAct=EBI-981051, EBI-702847; CC -!- SUBCELLULAR LOCATION: Capsid protein C: Virion CC {ECO:0000250|UniProtKB:P17763}. Host nucleus CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm CC {ECO:0000269|PubMed:19889084}. Host cytoplasm, host perinuclear CC region {ECO:0000269|PubMed:19889084}. CC -!- SUBCELLULAR LOCATION: Peptide pr: Secreted CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane CC protein {ECO:0000255}. Note=ER membrane retention is mediated by CC the transmembrane domains. {ECO:0000250|UniProtKB:P03314}. CC -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane CC {ECO:0000305}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane CC protein {ECO:0000255}. Note=ER membrane retention is mediated by CC the transmembrane domains. {ECO:0000250|UniProtKB:P03314}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum CC membrane; Peripheral membrane protein; Lumenal side CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived CC vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host CC endoplasmic reticulum membrane; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Serine protease NS3: Host endoplasmic CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; CC Peripheral membrane protein {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Cytoplasmic side {ECO:0000255|PROSITE- CC ProRule:PRU00860}. Note=Remains non-covalently associated to CC serine protease subunit NS2B. {ECO:0000255|PROSITE- CC ProRule:PRU00860}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4A: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P17763}. Note=Located in CC RE-associated vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P17763}. Note=Located in CC RE-derived vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host CC endoplasmic reticulum membrane; Peripheral membrane protein; CC Cytoplasmic side {ECO:0000250|UniProtKB:P17763}. Host nucleus CC {ECO:0000269|PubMed:16699025}. Note=Located in RE-associated CC vesicles hosting the replication complex. NS5 protein is mainly CC localized in the nucleus rather than in ER vesicles. CC {ECO:0000250|UniProtKB:P17763}. CC -!- DOMAIN: The transmembrane domains of the small envelope protein M CC and envelope protein E contain an endoplasmic reticulum retention CC signal. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: Genome polyprotein: Specific enzymatic cleavages in vivo CC yield mature proteins. Cleavages in the lumen of endoplasmic CC reticulum are performed by host signal peptidase, whereas CC cleavages in the cytoplasmic side are performed by serine protease CC NS3. Signal cleavage at the 2K-4B site requires a prior NS3 CC protease-mediated cleavage at the 4A-2K site. CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:17067286}. CC -!- PTM: Protein prM: Cleaved in post-Golgi vesicles by a host furin, CC releasing the mature small envelope protein M, and peptide pr. CC This cleavage is incomplete as up to 30% of viral particles still CC carry uncleaved prM. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: Envelope protein E: Not N-glycosylated. CC {ECO:0000269|PubMed:2441520}. CC -!- PTM: Non-structural protein 1: N-glycosylated. The excreted form CC is glycosylated and this is required for efficient secretion of CC the protein from infected cells. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: RNA-directed RNA polymerase NS5: Phosphorylated on serines CC residues. This phosphorylation may trigger NS5 nuclear CC localization. {ECO:0000250|UniProtKB:P17763}. CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like CC SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type CC methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M12294; AAA48498.2; -; Genomic_RNA. DR PIR; A25256; GNWVWV. DR RefSeq; NP_041724.2; NC_001563.2. DR PDB; 2FP7; X-ray; 1.68 A; A=1420-1466, B=1517-1688. DR PDB; 2G05; Model; -; D=1675-2120. DR PDB; 2G2G; Model; -; D=1675-2120. DR PDB; 2GGV; X-ray; 1.80 A; A=1419-1525, B=1503-1679. DR PDB; 2IJO; X-ray; 2.30 A; A=1419-1482, B=1502-1685. DR PDB; 2P5P; X-ray; 2.80 A; A/B/C=585-701. DR PDB; 2YOL; X-ray; 3.20 A; A=1420-1465, A=1502-1671. DR PDB; 3E90; X-ray; 2.45 A; A/C=1420-1463, B/D=1502-1685. DR PDB; 3I50; X-ray; 3.00 A; E=291-688. DR PDB; 5IDK; X-ray; 1.50 A; A/B/C=1420-1465. DR PDBsum; 2FP7; -. DR PDBsum; 2G05; -. DR PDBsum; 2G2G; -. DR PDBsum; 2GGV; -. DR PDBsum; 2IJO; -. DR PDBsum; 2P5P; -. DR PDBsum; 2YOL; -. DR PDBsum; 3E90; -. DR PDBsum; 3I50; -. DR PDBsum; 5IDK; -. DR DisProt; DP00673; -. DR SMR; P06935; -. DR IntAct; P06935; 4. DR BindingDB; P06935; -. DR ChEMBL; CHEMBL5419; -. DR MEROPS; S07.003; -. DR PRIDE; P06935; -. DR GeneID; 912267; -. DR KEGG; vg:912267; -. DR OrthoDB; 136at10239; -. DR BRENDA; 2.7.7.48; 6687. DR BRENDA; 3.4.21.91; 6687. DR EvolutionaryTrace; P06935; -. DR PRO; PR:P06935; -. DR Proteomes; UP000008600; Genome. DR GO; GO:0039714; C:cytoplasmic viral factory; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0032993; C:protein-DNA complex; IMP:CAFA. DR GO; GO:1990904; C:ribonucleoprotein complex; IMP:CAFA. DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008026; F:ATP-dependent helicase activity; IEA:InterPro. DR GO; GO:0003677; F:DNA binding; IMP:CAFA. DR GO; GO:1990814; F:DNA/DNA annealing activity; IMP:CAFA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0008233; F:peptidase activity; IDA:CACAO. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0003723; F:RNA binding; IMP:CAFA. DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro. DR GO; GO:0033592; F:RNA strand annealing activity; IMP:CAFA. DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IDA:UniProtKB. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW. DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:CACAO. DR GO; GO:0106005; P:RNA 5'-cap (guanine-N7)-methylation; IDA:UniProtKB. DR GO; GO:0043489; P:RNA stabilization; IMP:CAFA. DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IDA:CACAO. DR GO; GO:0039576; P:suppression by virus of host JAK1 activity; IEA:UniProtKB-KW. DR GO; GO:0039563; P:suppression by virus of host STAT1 activity; IEA:UniProtKB-KW. DR GO; GO:0039564; P:suppression by virus of host STAT2 activity; IEA:UniProtKB-KW. DR GO; GO:0039574; P:suppression by virus of host TYK2 activity; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR CDD; cd12149; Flavi_E_C; 1. DR Gene3D; 1.10.10.930; -; 1. DR Gene3D; 1.10.8.970; -; 1. DR Gene3D; 1.20.1280.260; -; 1. DR Gene3D; 2.60.260.50; -; 1. DR Gene3D; 2.60.40.350; -; 1. DR Gene3D; 2.60.98.10; -; 1. DR InterPro; IPR011492; DEAD_Flavivir. DR InterPro; IPR000069; Env_glycoprot_M_flavivir. DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir. DR InterPro; IPR001122; Flavi_capsidC. DR InterPro; IPR037172; Flavi_capsidC_sf. DR InterPro; IPR027287; Flavi_E_Ig-like. DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom. DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf. DR InterPro; IPR001157; Flavi_NS1. DR InterPro; IPR000752; Flavi_NS2A. DR InterPro; IPR000487; Flavi_NS2B. DR InterPro; IPR000404; Flavi_NS4A. DR InterPro; IPR001528; Flavi_NS4B. DR InterPro; IPR002535; Flavi_propep. DR InterPro; IPR038688; Flavi_propep_sf. DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf. DR InterPro; IPR001850; Flavivirus_NS3_S7. DR InterPro; IPR014412; Gen_Poly_FLV. DR InterPro; IPR011998; Glycoprot_cen/dimer. DR InterPro; IPR036253; Glycoprot_cen/dimer_sf. DR InterPro; IPR038055; Glycoprot_E_dimer_dom. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR000208; RNA-dir_pol_flavivirus. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR002877; rRNA_MeTrfase_FtsJ_dom. DR InterPro; IPR029063; SAM-dependent_MTases. DR Pfam; PF01003; Flavi_capsid; 1. DR Pfam; PF07652; Flavi_DEAD; 1. DR Pfam; PF02832; Flavi_glycop_C; 1. DR Pfam; PF00869; Flavi_glycoprot; 1. DR Pfam; PF01004; Flavi_M; 1. DR Pfam; PF00948; Flavi_NS1; 1. DR Pfam; PF01005; Flavi_NS2A; 1. DR Pfam; PF01002; Flavi_NS2B; 1. DR Pfam; PF01350; Flavi_NS4A; 1. DR Pfam; PF01349; Flavi_NS4B; 1. DR Pfam; PF00972; Flavi_NS5; 1. DR Pfam; PF01570; Flavi_propep; 1. DR Pfam; PF01728; FtsJ; 1. DR Pfam; PF00949; Peptidase_S7; 1. DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF101257; SSF101257; 1. DR SUPFAM; SSF50494; SSF50494; 1. DR SUPFAM; SSF52540; SSF52540; 2. DR SUPFAM; SSF53335; SSF53335; 1. DR SUPFAM; SSF56983; SSF56983; 1. DR SUPFAM; SSF81296; SSF81296; 1. DR TIGRFAMs; TIGR04240; flavi_E_stem; 1. DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1. DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1. PE 1: Evidence at protein level; KW 3D-structure; Activation of host autophagy by virus; ATP-binding; KW Capsid protein; Clathrin-mediated endocytosis of virus by host; KW Cleavage on pair of basic residues; Complete proteome; Disulfide bond; KW Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; Helicase; KW Host cytoplasm; Host endoplasmic reticulum; Host membrane; KW Host nucleus; Host-virus interaction; Hydrolase; KW Inhibition of host innate immune response by virus; KW Inhibition of host interferon signaling pathway by virus; KW Inhibition of host JAK1 by virus; Inhibition of host STAT1 by virus; KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus; KW Membrane; Metal-binding; Methyltransferase; mRNA capping; KW mRNA processing; Multifunctional enzyme; Nucleotide-binding; KW Nucleotidyltransferase; Phosphoprotein; Protease; RNA-binding; KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Secreted; KW Serine protease; Suppressor of RNA silencing; Transcription; KW Transcription regulation; Transferase; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; KW Viral envelope protein; Viral immunoevasion; KW Viral penetration into host cytoplasm; Viral RNA replication; Virion; KW Virus endocytosis by host; Virus entry into host cell; Zinc. FT CHAIN 1 3430 Genome polyprotein. FT /FTId=PRO_0000441418. FT CHAIN 1 105 Capsid protein C. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037743. FT PROPEP 106 123 ER anchor for the capsid protein C, FT removed in mature form by serine protease FT NS3. {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037744. FT CHAIN 124 290 Protein prM. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000405150. FT CHAIN 124 215 Peptide pr. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000405151. FT CHAIN 216 290 Small envelope protein M. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037745. FT CHAIN 291 787 Envelope protein E. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037746. FT CHAIN 788 1139 Non-structural protein 1. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037747. FT CHAIN 1140 1370 Non-structural protein 2A. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037748. FT CHAIN 1371 1501 Serine protease subunit NS2B. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037749. FT CHAIN 1502 2120 Serine protease NS3. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037750. FT CHAIN 2121 2246 Non-structural protein 4A. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037751. FT PEPTIDE 2247 2269 Peptide 2k. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000405152. FT CHAIN 2270 2525 Non-structural protein 4B. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037752. FT CHAIN 2526 3430 RNA-directed RNA polymerase NS5. FT {ECO:0000269|PubMed:17067286}. FT /FTId=PRO_0000037753. FT TOPO_DOM 2 105 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 106 126 Helical. {ECO:0000255}. FT TOPO_DOM 127 248 Extracellular. {ECO:0000255}. FT TRANSMEM 249 269 Helical. {ECO:0000255}. FT TOPO_DOM 270 275 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 276 290 Helical. {ECO:0000305}. FT TOPO_DOM 291 739 Extracellular. {ECO:0000255}. FT TRANSMEM 740 760 Helical. {ECO:0000255}. FT TOPO_DOM 761 766 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 767 787 Helical. {ECO:0000255}. FT TOPO_DOM 788 1212 Extracellular. {ECO:0000255}. FT TRANSMEM 1213 1233 Helical. {ECO:0000255}. FT TOPO_DOM 1234 1243 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1244 1264 Helical. {ECO:0000255}. FT TOPO_DOM 1265 1278 Lumenal. {ECO:0000255}. FT TRANSMEM 1279 1299 Helical. {ECO:0000255}. FT TOPO_DOM 1300 1307 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1308 1328 Helical. {ECO:0000255}. FT TOPO_DOM 1329 1340 Lumenal. {ECO:0000255}. FT TRANSMEM 1341 1361 Helical. {ECO:0000255}. FT TOPO_DOM 1362 1371 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1372 1392 Helical. {ECO:0000255}. FT TOPO_DOM 1393 1395 Lumenal. {ECO:0000255}. FT TRANSMEM 1396 1416 Helical. {ECO:0000255}. FT TOPO_DOM 1417 1473 Cytoplasmic. {ECO:0000255}. FT INTRAMEM 1474 1494 Helical. {ECO:0000255}. FT TOPO_DOM 1495 2170 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2171 2191 Helical. {ECO:0000255}. FT TOPO_DOM 2192 2196 Lumenal. {ECO:0000255}. FT INTRAMEM 2197 2217 Helical. {ECO:0000255}. FT TOPO_DOM 2218 2218 Lumenal. {ECO:0000255}. FT TRANSMEM 2219 2239 Helical. {ECO:0000255}. FT TOPO_DOM 2240 2254 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2255 2275 Helical; Note=Signal for NS4B. FT {ECO:0000255}. FT TOPO_DOM 2276 2309 Lumenal. {ECO:0000255}. FT INTRAMEM 2310 2330 Helical. {ECO:0000255}. FT TOPO_DOM 2331 2377 Lumenal. {ECO:0000255}. FT TRANSMEM 2378 2398 Helical. {ECO:0000255}. FT TOPO_DOM 2399 2441 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2442 2462 Helical. {ECO:0000255}. FT TOPO_DOM 2463 2467 Lumenal. {ECO:0000255}. FT TRANSMEM 2468 2488 Helical. {ECO:0000255}. FT TOPO_DOM 2489 3430 Cytoplasmic. {ECO:0000255}. FT DOMAIN 1502 1679 Peptidase S7. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT DOMAIN 1682 1838 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 1849 2014 Helicase C-terminal. FT {ECO:0000255|PROSITE-ProRule:PRU00542}. FT DOMAIN 2526 2791 mRNA cap 0-1 NS5-type MT. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT DOMAIN 3055 3207 RdRp catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU00539}. FT NP_BIND 1695 1702 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 2 15 Interaction with host EXOC1. FT {ECO:0000269|PubMed:19889084}. FT REGION 37 72 Hydrophobic; homodimerization of capsid FT protein C. FT {ECO:0000250|UniProtKB:P29990}. FT REGION 388 401 Fusion peptide. FT {ECO:0000250|UniProtKB:P14336}. FT REGION 1424 1463 Interacts with and activates NS3 FT protease. {ECO:0000255|PROSITE- FT ProRule:PRU00859}. FT REGION 1686 1689 Important for RNA-binding. FT {ECO:0000250|UniProtKB:P14340}. FT REGION 2165 2169 Regulates the ATPase activity of NS3 FT helicase. {ECO:0000250|UniProtKB:Q9Q6P4}. FT MOTIF 1786 1789 DEAH box. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT COMPBIAS 281 284 Poly-Leu. FT COMPBIAS 2675 2678 Poly-Ser. FT ACT_SITE 1552 1552 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1576 1576 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1636 1636 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 2586 2586 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2671 2671 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2707 2707 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2743 2743 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2965 2965 Zinc 1. {ECO:0000250|UniProtKB:P14335}. FT METAL 2969 2969 Zinc 1; via tele nitrogen. FT {ECO:0000250|UniProtKB:P14335}. FT METAL 2974 2974 Zinc 1. {ECO:0000250|UniProtKB:P14335}. FT METAL 2977 2977 Zinc 1. {ECO:0000250|UniProtKB:P14335}. FT METAL 3242 3242 Zinc 2; via tele nitrogen. FT {ECO:0000250|UniProtKB:P14335}. FT METAL 3258 3258 Zinc 2. {ECO:0000250|UniProtKB:P14335}. FT METAL 3377 3377 Zinc 2. {ECO:0000250|UniProtKB:P14335}. FT BINDING 2581 2581 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2611 2611 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2612 2612 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2629 2629 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2630 2630 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2656 2656 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2657 2657 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2672 2672 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2745 2745 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 105 106 Cleavage; by viral protease NS3. FT {ECO:0000269|PubMed:17067286}. FT SITE 123 124 Cleavage; by host signal peptidase. FT {ECO:0000269|PubMed:17067286}. FT SITE 215 216 Cleavage; by host furin. FT {ECO:0000303|PubMed:17067286}. FT SITE 290 291 Cleavage; by host signal peptidase. FT {ECO:0000303|PubMed:17067286}. FT SITE 787 788 Cleavage; by host signal peptidase. FT {ECO:0000303|PubMed:17067286}. FT SITE 1139 1140 Cleavage; by host. FT {ECO:0000303|PubMed:17067286}. FT SITE 1370 1371 Cleavage; by viral protease NS3. FT {ECO:0000269|PubMed:17067286}. FT SITE 1501 1502 Cleavage; by autolysis. FT {ECO:0000269|PubMed:17067286}. FT SITE 1959 1959 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 1962 1962 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 2120 2121 Cleavage; by autolysis. FT {ECO:0000303|PubMed:17067286}. FT SITE 2246 2247 Cleavage; by viral protease NS3. FT {ECO:0000303|PubMed:17067286}. FT SITE 2269 2270 Cleavage; by host signal peptidase. FT {ECO:0000303|PubMed:17067286}. FT SITE 2525 2526 Cleavage; by viral protease NS3. FT {ECO:0000269|PubMed:17067286}. FT SITE 2538 2538 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2541 2541 mRNA cap binding; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2542 2542 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2544 2544 mRNA cap binding; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2549 2549 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924, FT ECO:0000269|PubMed:17067286}. FT SITE 2553 2553 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2586 2586 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2671 2671 Essential for 2'-O-methyltransferase and FT N-7 methyltransferase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2675 2675 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2707 2707 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2738 2738 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2740 2740 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2743 2743 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT MOD_RES 2581 2581 Phosphoserine. FT {ECO:0000250|UniProtKB:P03314}. FT CARBOHYD 138 138 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000250|UniProtKB:P14335}. FT CARBOHYD 917 917 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000250|UniProtKB:Q9Q6P4}. FT CARBOHYD 962 962 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000250|UniProtKB:Q9Q6P4}. FT CARBOHYD 994 994 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 293 320 {ECO:0000269|PubMed:3811228}. FT DISULFID 350 411 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 350 406 {ECO:0000269|PubMed:3811228}. FT DISULFID 364 395 {ECO:0000269|PubMed:3811228}. FT DISULFID 382 411 {ECO:0000269|PubMed:3811228}. FT DISULFID 382 406 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 476 574 {ECO:0000269|PubMed:3811228}. FT DISULFID 591 622 {ECO:0000269|PubMed:3811228}. FT DISULFID 791 802 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 842 930 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 966 1010 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 1067 1116 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 1078 1099 {ECO:0000250|UniProtKB:Q9Q6P4}. FT DISULFID 1100 1103 {ECO:0000250|UniProtKB:Q9Q6P4}. FT MUTAGEN 14 14 V->A: Loss of interaction between capsid FT protein C and host EXOC1. FT {ECO:0000269|PubMed:23522008}. FT MUTAGEN 2586 2586 K->A: Complete loss of 2'-O- FT methyltransferase activity. No effect on FT N-7 methyltransferase activity. FT {ECO:0000269|PubMed:17267492}. FT MUTAGEN 2671 2671 D->A: Lethal for the virus. Complete loss FT of 2'-O and N-7 methyltransferase FT activies. {ECO:0000269|PubMed:17267492}. FT MUTAGEN 2707 2707 K->A: Complete loss of 2'-O- FT methyltransferase activity. No effect on FT N-7 methyltransferase activity. FT {ECO:0000269|PubMed:17267492}. FT MUTAGEN 2743 2743 E->A: Complete loss of 2'-O- FT methyltransferase activity. No effect on FT N-7 methyltransferase activity. FT {ECO:0000269|PubMed:17267492}. FT STRAND 595 603 {ECO:0000244|PDB:2P5P}. FT STRAND 605 607 {ECO:0000244|PDB:2P5P}. FT STRAND 609 615 {ECO:0000244|PDB:2P5P}. FT STRAND 621 623 {ECO:0000244|PDB:2P5P}. FT STRAND 626 631 {ECO:0000244|PDB:2P5P}. FT STRAND 634 637 {ECO:0000244|PDB:2P5P}. FT STRAND 639 643 {ECO:0000244|PDB:2P5P}. FT STRAND 657 662 {ECO:0000244|PDB:2P5P}. FT STRAND 665 673 {ECO:0000244|PDB:2P5P}. FT STRAND 679 685 {ECO:0000244|PDB:2P5P}. FT STRAND 1422 1428 {ECO:0000244|PDB:5IDK}. FT HELIX 1434 1439 {ECO:0000244|PDB:2GGV}. FT STRAND 1440 1443 {ECO:0000244|PDB:2GGV}. FT STRAND 1444 1449 {ECO:0000244|PDB:5IDK}. FT STRAND 1451 1453 {ECO:0000244|PDB:2YOL}. FT STRAND 1455 1457 {ECO:0000244|PDB:5IDK}. FT STRAND 1503 1505 {ECO:0000244|PDB:5IDK}. FT STRAND 1521 1532 {ECO:0000244|PDB:5IDK}. FT STRAND 1534 1543 {ECO:0000244|PDB:5IDK}. FT STRAND 1546 1549 {ECO:0000244|PDB:5IDK}. FT HELIX 1551 1554 {ECO:0000244|PDB:5IDK}. FT STRAND 1559 1561 {ECO:0000244|PDB:5IDK}. FT STRAND 1564 1566 {ECO:0000244|PDB:5IDK}. FT STRAND 1568 1572 {ECO:0000244|PDB:5IDK}. FT TURN 1573 1576 {ECO:0000244|PDB:5IDK}. FT STRAND 1577 1583 {ECO:0000244|PDB:5IDK}. FT STRAND 1592 1594 {ECO:0000244|PDB:5IDK}. FT STRAND 1596 1600 {ECO:0000244|PDB:5IDK}. FT STRAND 1608 1612 {ECO:0000244|PDB:5IDK}. FT STRAND 1615 1618 {ECO:0000244|PDB:5IDK}. FT STRAND 1623 1627 {ECO:0000244|PDB:5IDK}. FT HELIX 1633 1635 {ECO:0000244|PDB:2FP7}. FT STRAND 1639 1641 {ECO:0000244|PDB:5IDK}. FT STRAND 1647 1650 {ECO:0000244|PDB:5IDK}. FT STRAND 1654 1656 {ECO:0000244|PDB:5IDK}. FT STRAND 1662 1665 {ECO:0000244|PDB:5IDK}. FT STRAND 1672 1674 {ECO:0000244|PDB:2IJO}. SQ SEQUENCE 3430 AA; 380110 MW; 42D71B7CB12DC45B CRC64; MSKKPGGPGK NRAVNMLKRG MPRGLSLIGL KRAMLSLIDG KGPIRFVLAL LAFFRFTAIA PTRAVLDRWR GVNKQTAMKH LLSFKKELGT LTSAINRRST KQKKRGGTAG FTILLGLIAC AGAVTLSNFQ GKVMMTVNAT DVTDVITIPT AAGKNLCIVR AMDVGYLCED TITYECPVLA AGNDPEDIDC WCTKSSVYVR YGRCTKTRHS RRSRRSLTVQ THGESTLANK KGAWLDSTKA TRYLVKTESW ILRNPGYALV AAVIGWMLGS NTMQRVVFAI LLLLVAPAYS FNCLGMSNRD FLEGVSGATW VDLVLEGDSC VTIMSKDKPT IDVKMMNMEA ANLADVRSYC YLASVSDLST RAACPTMGEA HNEKRADPAF VCKQGVVDRG WGNGCGLFGK GSIDTCAKFA CTTKATGWII QKENIKYEVA IFVHGPTTVE SHGKIGATQA GRFSITPSAP SYTLKLGEYG EVTVDCEPRS GIDTSAYYVM SVGEKSFLVH REWFMDLNLP WSSAGSTTWR NRETLMEFEE PHATKQSVVA LGSQEGALHQ ALAGAIPVEF SSNTVKLTSG HLKCRVKMEK LQLKGTTYGV CSKAFKFART PADTGHGTVV LELQYTGTDG PCKVPISSVA SLNDLTPVGR LVTVNPFVSV ATANSKVLIE LEPPFGDSYI VVGRGEQQIN HHWHKSGSSI GKAFTTTLRG AQRLAALGDT AWDFGSVGGV FTSVGKAIHQ VFGGAFRSLF GGMSWITQGL LGALLLWMGI NARDRSIAMT FLAVGGVLLF LSVNVHADTG CAIDIGRQEL RCGSGVFIHN DVEAWMDRYK FYPETPQGLA KIIQKAHAEG VCGLRSVSRL EHQMWEAIKD ELNTLLKENG VDLSVVVEKQ NGMYKAAPKR LAATTEKLEM GWKAWGKSII FAPELANNTF VIDGPETEEC PTANRAWNSM EVEDFGFGLT STRMFLRIRE TNTTECDSKI IGTAVKNNMA VHSDLSYWIE SGLNDTWKLE RAVLGEVKSC TWPETHTLWG DGVLESDLII PITLAGPRSN HNRRPGYKTQ NQGPWDEGRV EIDFDYCPGT TVTISDSCEH RGPAARTTTE SGKLITDWCC RSCTLPPLRF QTENGCWYGM EIRPTRHDEK TLVQSRVNAY NADMIDPFQL GLMVVFLATQ EVLRKRWTAK ISIPAIMLAL LVLVFGGITY TDVLRYVILV GAAFAEANSG GDVVHLALMA TFKIQPVFLV ASFLKARWTN QESILLMLAA AFFQMAYYDA KNVLSWEVPD VLNSLSVAWM ILRAISFTNT SNVVVPLLAL LTPGLKCLNL DVYRILLLMV GVGSLIKEKR SSAAKKKGAC LICLALASTG VFNPMILAAG LMACDPNRKR GWPATEVMTA VGLMFAIVGG LAELDIDSMA IPMTIAGLMF AAFVISGKST DMWIERTADI TWESDAEITG SSERVDVRLD DDGNFQLMND PGAPWKIWML RMACLAISAY TPWAILPSVI GFWITLQYTK RGGVLWDTPS PKEYKKGDTT TGVYRIMTRG LLGSYQAGAG VMVEGVFHTL WHTTKGAALM SGEGRLDPYW GSVKEDRLCY GGPWKLQHKW NGHDEVQMIV VEPGKNVKNV QTKPGVFKTP EGEIGAVTLD YPTGTSGSPI VDKNGDVIGL YGNGVIMPNG SYISAIVQGE RMEEPAPAGF EPEMLRKKQI TVLDLHPGAG KTRKILPQII KEAINKRLRT AVLAPTRVVA AEMSEALRGL PIRYQTSAVH REHSGNEIVD VMCHATLTHR LMSPHRVPNY NLFIMDEAHF TDPASIAARG YIATKVELGE AAAIFMTATP PGTSDPFPES NAPISDMQTE IPDRAWNTGY EWITEYVGKT VWFVPSVKMG NEIALCLQRA GKKVIQLNRK SYETEYPKCK NDDWDFVITT DISEMGANFK ASRVIDSRKS VKPTIIEEGD GRVILGEPSA ITAASAAQRR GRIGRNPSQV GDEYCYGGHT NEDDSNFAHW TEARIMLDNI NMPNGLVAQL YQPEREKVYT MDGEYRLRGE ERKNFLEFLR TADLPVWLAY KVAAAGISYH DRKWCFDGPR TNTILEDNNE VEVITKLGER KILRPRWADA RVYSDHQALK SFKDFASGKR SQIGLVEVLG RMPEHFMVKT WEALDTMYVV ATAEKGGRAH RMALEELPDA LQTIVLIALL SVMSLGVFFL LMQRKGIGKI GLGGVILGAA TFFCWMAEVP GTKIAGMLLL SLLLMIVLIP EPEKQRSQTD NQLAVFLICV LTLVGAVAAN EMGWLDKTKN DIGSLLGHRP EARETTLGVE SFLLDLRPAT AWSLYAVTTA VLTPLLKHLI TSDYINTSLT SINVQASALF TLARGFPFVD VGVSALLLAV GCWGQVTLTV TVTAAALLFC HYAYMVPGWQ AEAMRSAQRR TAAGIMKNVV VDGIVATDVP ELERTTPVMQ KKVGQIILIL VSMAAVVVNP SVRTVREAGI LTTAAAVTLW ENGASSVWNA TTAIGLCHIM RGGWLSCLSI MWTLIKNMEK PGLKRGGAKG RTLGEVWKER LNHMTKEEFT RYRKEAITEV DRSAAKHARR EGNITGGHPV SRGTAKLRWL VERRFLEPVG KVVDLGCGRG GWCYYMATQK RVQEVKGYTK GGPGHEEPQL VQSYGWNIVT MKSGVDVFYR PSEASDTLLC DIGESSSSAE VEEHRTVRVL EMVEDWLHRG PKEFCIKVLC PYMPKVIEKM ETLQRRYGGG LIRNPLSRNS THEMYWVSHA SGNIVHSVNM TSQVLLGRME KKTWKGPQFE EDVNLGSGTR AVGKPLLNSD TSKIKNRIER LKKEYSSTWH QDANHPYRTW NYHGSYEVKP TGSASSLVNG VVRLLSKPWD TITNVTTMAM TDTTPFGQQR VFKEKVDTKA PEPPEGVKYV LNETTNWLWA FLARDKKPRM CSREEFIGKV NSNAALGAMF EEQNQWKNAR EAVEDPKFWE MVDEEREAHL RGECNTCIYN MMGKREKKPG EFGKAKGSRA IWFMWLGARF LEFEALGFLN EDHWLGRKNS GGGVEGLGLQ KLGYILKEVG TKPGGKVYAD DTAGWDTRIT KADLENEAKV LELLDGEHRR LARSIIELTY RHKVVKVMRP AADGKTVMDV ISREDQRGSG QVVTYALNTF TNLAVQLVRM MEGEGVIGPD DVEKLGKGKG PKVRTWLFEN GEERLSRMAV SGDDCVVKPL DDRFATSLHF LNAMSKVRKD IQEWKPSTGW YDWQQVPFCS NHFTELIMKD GRTLVVPCRG QDELIGRARI SPGAGWNVRD TACLAKSYAQ MWLLLYFHRR DLRLMANAIC SAVPANWVPT GRTTWSIHAK GEWMTTEDML AVWNRVWIEE NEWMEDKTPV ERWSDVPYSG KREDIWCGSL IGTRTRATWA ENIHVAINQV RSVIGEEKYV DYMSSLRRYE DTIVVEDTVL //