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 26-FEB-2020, entry version 190. 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; Riboviria; 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 for all RT 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., 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-associated RT proteins V1 and NV2 of the flavivirus West Nile virus and of the genome RT 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 Nile RT virus and of its gene."; RL Virology 147:264-274(1985). RN [5] RP ABSENCE OF GLYCOSYLATION (ENVELOPE PROTEIN E). RX PubMed=2441520; DOI=10.1016/0042-6822(87)90460-0; 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 Nile RT 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-mediated RT 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 LYS-2586; RP 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., Bernard K.A., RA 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 LOCATION RP (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 repressor RT of flavivirus."; RL Cell. Microbiol. 12:453-472(2010). RN [12] RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), FUNCTION (CAPSID PROTEIN RP 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 proteases RT 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., Chipman P.R., RA Kuhn R.J., Diamond M.S., Rossmann M.G., Fremont D.H.; RT "Structural basis for the preferential recognition of immature flaviviruses RT by a fusion-loop antibody."; RL EMBO J. 28:3269-3276(2009). CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding CC to the cell membrane and gathering the viral RNA into a nucleocapsid CC that forms the core of a mature virus particle (By similarity). During CC virus entry, may induce genome penetration into the host cytoplasm CC after hemifusion induced by the surface proteins (By similarity). Can CC migrate to the cell nucleus where it modulates host functions (By CC similarity). Overcomes the anti-viral effects of host EXOC1 by CC sequestering and degrading the latter through the proteasome CC degradation pathway (PubMed:23522008). {ECO:0000250|UniProtKB:P17763, CC 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 envelope CC proteins in trans-Golgi by binding to envelope protein E at pH6.0. CC After virion release in extracellular space, gets dissociated from E CC 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 Golgi CC compartment prior to virion release. prM-E cleavage is inefficient, and CC many virions are only partially matured. These uncleaved prM would play CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding. CC Exerts cytotoxic effects by activating a mitochondrial apoptotic CC pathway through M ectodomain. May display a viroporin activity. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and CC mediates fusion between viral and cellular membranes (PubMed:15367621). CC Envelope protein is synthesized in the endoplasmic reticulum in the CC form of heterodimer with protein prM (By similarity). They play a role CC in virion budding in the ER, and the newly formed immature particle is CC covered with 60 spikes composed of heterodimer between precursor prM CC and envelope protein E (By similarity). The virion is transported to CC the Golgi 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 matured CC (By similarity). These uncleaved prM would play a role in immune CC 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 polyprotein, CC is targeted to three destinations: the viral replication cycle, the CC plasma membrane and the extracellular compartment. Essential for viral CC replication. Required for formation of the replication complex and CC recruitment of other non-structural proteins to the ER-derived membrane CC structures. Excreted as a hexameric lipoparticle that plays a role CC against host immune response. Antagonizing the complement function. CC Binds 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 antagonizes CC 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-ProRule:PRU00859}. CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities: CC serine protease, NTPase and RNA helicase. NS3 serine protease, in CC association with NS2B, performs its autocleavage and cleaves the CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B- CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and CC unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE- CC ProRule:PRU00860}. CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy CC during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is CC 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 cellular CC antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 CC translocation in the nucleus after IFN-alpha treatment. CC {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 guanine N- CC 7 and ribose 2'-O positions (PubMed:17267492). Besides its role in RNA CC genome replication, also prevents the establishment of cellular CC antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) CC signaling pathway (By similarity). Inhibits host TYK2 and STAT2 CC phosphorylation, thereby preventing activation of JAK-STAT signaling CC pathway (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4, CC ECO:0000269|PubMed:17267492}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of CC the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.; CC 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, ChEBI:CHEBI:83400; CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- CC 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'-end (5'-triphosphoguanosine)-guanosine in mRNA + S- CC adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-guanosine in mRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60856, Rhea:RHEA-COMP:15681, Rhea:RHEA-COMP:15683, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:143971, CC ChEBI:CHEBI:143975; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00924}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (5'-triphosphoguanosine)-adenosine in mRNA + S- CC adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-adenosine in mRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60852, Rhea:RHEA-COMP:15680, Rhea:RHEA-COMP:15682, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:143973, CC ChEBI:CHEBI:143974; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00924}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-guanosine in CC mRNA + S-adenosyl-L-methionine = a 5'-end (N7-methyl 5'- CC triphosphoguanosine)-(2'-O-methyl-guanosine) in mRNA + H(+) + S- CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:60864, Rhea:RHEA-COMP:15683, CC Rhea:RHEA-COMP:15685, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:143975, ChEBI:CHEBI:143977; CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-adenosine in CC mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-(2'-O-methyl-adenosine) in mRNA + H(+) + S- CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:60860, Rhea:RHEA-COMP:15682, CC Rhea:RHEA-COMP:15684, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:143974, ChEBI:CHEBI:143976; CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; CC -!- SUBUNIT: [Capsid protein C]: Homodimer (By similarity). Interacts (via CC N-terminus) with host EXOC1 (via C-terminus) (PubMed:19889084, CC PubMed:23522008); this interaction results in EXOC1 degradation through CC the proteasome degradation pathway (PubMed:23522008). CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:19889084, CC ECO:0000269|PubMed:23522008}. CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in CC the endoplasmic reticulum and Golgi (By similarity). CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum CC and Golgi (By similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when CC secreted (By similarity). Interacts with envelope protein E (By CC similarity). NS1 interacts with NS4B (By similarity). Interacts with CC host complement protein CFH; this interaction leads to the degradation CC of C3 (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with CC serine protease NS3. {ECO:0000250|UniProtKB:P03314}. CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with CC serine protease NS3 (By similarity). May form homooligomers (By CC similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B (By CC similarity). Interacts with NS4B (By similarity). Interacts with CC unphosphorylated RNA-directed RNA polymerase NS5; this interaction CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity CC (By similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease CC NS3. Interacts with NS1 (By similarity). CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer (By similarity). CC Interacts with host STAT2; this interaction inhibits the CC phosphorylation of the latter, and, when all viral proteins are present CC (polyprotein), targets STAT2 for degradation (By similarity). CC {ECO:0000250|UniProtKB:P17763}. 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 region CC {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 membrane CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein CC {ECO:0000255}. Note=ER membrane retention is mediated by the CC 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 membrane CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein CC {ECO:0000255}. Note=ER membrane retention is mediated by the CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane; CC Peripheral membrane protein; Lumenal side CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic CC reticulum membrane; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently CC associated to 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 membrane CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated CC 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 membrane CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived CC 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 vesicles CC hosting the replication complex. NS5 protein is mainly localized in the CC nucleus rather than in ER vesicles. {ECO:0000250|UniProtKB:P17763}. CC -!- DOMAIN: The transmembrane domains of the small envelope protein M and CC envelope protein E contain an endoplasmic reticulum retention signal. CC {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield CC mature proteins. Cleavages in the lumen of endoplasmic reticulum are CC performed by host signal peptidase, whereas cleavages in the CC cytoplasmic side are performed by serine protease NS3. Signal cleavage CC at the 2K-4B site requires a prior NS3 protease-mediated cleavage at CC the 4A-2K site. {ECO:0000250|UniProtKB:P17763, CC 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. This CC cleavage is incomplete as up to 30% of viral particles still carry CC 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 is CC glycosylated and this is required for efficient secretion of the CC 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 localization. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM- CC 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 SMR; P06935; -. DR IntAct; P06935; 4. DR BindingDB; P06935; -. DR ChEMBL; CHEMBL5419; -. DR MEROPS; S07.003; -. DR PRIDE; P06935; -. DR ABCD; 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: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:UniProtKB-EC. 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 DisProt; DP00673; -. 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; 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; Host nucleus; KW 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; mRNA processing; KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; KW Phosphoprotein; Protease; RNA-binding; RNA-directed RNA polymerase; KW S-adenosyl-L-methionine; Secreted; Serine protease; KW Suppressor of RNA silencing; Transcription; Transcription regulation; KW Transferase; Transmembrane; Transmembrane helix; KW Viral attachment to host cell; 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 FT /note="Genome polyprotein" FT /id="PRO_0000441418" FT CHAIN 1..105 FT /note="Capsid protein C" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037743" FT PROPEP 106..123 FT /note="ER anchor for the capsid protein C, removed in FT mature form by serine protease NS3" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037744" FT CHAIN 124..290 FT /note="Protein prM" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000405150" FT CHAIN 124..215 FT /note="Peptide pr" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000405151" FT CHAIN 216..290 FT /note="Small envelope protein M" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037745" FT CHAIN 291..787 FT /note="Envelope protein E" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037746" FT CHAIN 788..1139 FT /note="Non-structural protein 1" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037747" FT CHAIN 1140..1370 FT /note="Non-structural protein 2A" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037748" FT CHAIN 1371..1501 FT /note="Serine protease subunit NS2B" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037749" FT CHAIN 1502..2120 FT /note="Serine protease NS3" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037750" FT CHAIN 2121..2246 FT /note="Non-structural protein 4A" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037751" FT PEPTIDE 2247..2269 FT /note="Peptide 2k" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000405152" FT CHAIN 2270..2525 FT /note="Non-structural protein 4B" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037752" FT CHAIN 2526..3430 FT /note="RNA-directed RNA polymerase NS5" FT /evidence="ECO:0000269|PubMed:17067286" FT /id="PRO_0000037753" FT TOPO_DOM 2..105 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 106..126 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 127..248 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 249..269 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 270..275 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 276..290 FT /note="Helical" FT /evidence="ECO:0000305" FT TOPO_DOM 291..739 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 740..760 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 761..766 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 767..787 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 788..1212 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1213..1233 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1234..1243 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1244..1264 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1265..1278 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1279..1299 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1300..1307 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1308..1328 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1329..1340 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1341..1361 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1362..1371 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1372..1392 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1393..1395 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1396..1416 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1417..1473 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 1474..1494 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1495..2170 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2171..2191 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2192..2196 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2197..2217 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2218 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2219..2239 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2240..2254 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2255..2275 FT /note="Helical; Note=Signal for NS4B" FT /evidence="ECO:0000255" FT TOPO_DOM 2276..2309 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2310..2330 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2331..2377 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2378..2398 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2399..2441 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2442..2462 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2463..2467 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2468..2488 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2489..3430 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 1502..1679 FT /note="Peptidase S7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT DOMAIN 1682..1838 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 1849..2014 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 2526..2791 FT /note="mRNA cap 0-1 NS5-type MT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT DOMAIN 3055..3207 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT NP_BIND 1695..1702 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT REGION 2..15 FT /note="Interaction with host EXOC1" FT /evidence="ECO:0000269|PubMed:19889084" FT REGION 37..72 FT /note="Hydrophobic; homodimerization of capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT REGION 388..401 FT /note="Fusion peptide" FT /evidence="ECO:0000250|UniProtKB:P14336" FT REGION 1424..1463 FT /note="Interacts with and activates NS3 protease" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859" FT REGION 1686..1689 FT /note="Important for RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P14340" FT REGION 2165..2169 FT /note="Regulates the ATPase activity of NS3 helicase" FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT MOTIF 1786..1789 FT /note="DEAH box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT COMPBIAS 281..284 FT /note="Poly-Leu" FT COMPBIAS 2675..2678 FT /note="Poly-Ser" FT ACT_SITE 1552 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1576 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1636 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 2586 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2671 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2707 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2743 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2965 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 2969 FT /note="Zinc 1; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 2974 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 2977 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 3242 FT /note="Zinc 2; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 3258 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:P14335" FT METAL 3377 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 2581 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2611 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2612 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2629 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2630 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2656 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2657 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2672 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2745 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 105..106 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:17067286" FT SITE 123..124 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000269|PubMed:17067286" FT SITE 215..216 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 290..291 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 787..788 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 1139..1140 FT /note="Cleavage; by host" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 1370..1371 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:17067286" FT SITE 1501..1502 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:17067286" FT SITE 1959 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 1962 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 2120..2121 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 2246..2247 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 2269..2270 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000303|PubMed:17067286" FT SITE 2525..2526 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:17067286" FT SITE 2538 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2541 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2542 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2544 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2549 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:17067286" FT SITE 2553 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2586 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2671 FT /note="Essential for 2'-O-methyltransferase and N-7 FT methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2675 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2707 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2738 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2740 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2743 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT MOD_RES 2581 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P03314" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:P14335" FT CARBOHYD 917 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT CARBOHYD 962 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT CARBOHYD 994 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 293..320 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 350..411 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 350..406 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 364..395 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 382..411 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 382..406 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 476..574 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 591..622 FT /evidence="ECO:0000269|PubMed:3811228" FT DISULFID 791..802 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 842..930 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 966..1010 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 1067..1116 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 1078..1099 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT DISULFID 1100..1103 FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4" FT MUTAGEN 14 FT /note="V->A: Loss of interaction between capsid protein C FT and host EXOC1." FT /evidence="ECO:0000269|PubMed:23522008" FT MUTAGEN 2586 FT /note="K->A: Complete loss of 2'-O-methyltransferase FT activity. No effect on N-7 methyltransferase activity." FT /evidence="ECO:0000269|PubMed:17267492" FT MUTAGEN 2671 FT /note="D->A: Lethal for the virus. Complete loss of 2'-O FT and N-7 methyltransferase activies." FT /evidence="ECO:0000269|PubMed:17267492" FT MUTAGEN 2707 FT /note="K->A: Complete loss of 2'-O-methyltransferase FT activity. No effect on N-7 methyltransferase activity." FT /evidence="ECO:0000269|PubMed:17267492" FT MUTAGEN 2743 FT /note="E->A: Complete loss of 2'-O-methyltransferase FT activity. No effect on N-7 methyltransferase activity." FT /evidence="ECO:0000269|PubMed:17267492" FT STRAND 595..603 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 605..607 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 609..615 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 621..623 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 626..631 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 634..637 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 639..643 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 657..662 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 665..673 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 679..685 FT /evidence="ECO:0000244|PDB:2P5P" FT STRAND 1422..1428 FT /evidence="ECO:0000244|PDB:5IDK" FT HELIX 1434..1439 FT /evidence="ECO:0000244|PDB:2GGV" FT STRAND 1440..1443 FT /evidence="ECO:0000244|PDB:2GGV" FT STRAND 1444..1449 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1451..1453 FT /evidence="ECO:0000244|PDB:2YOL" FT STRAND 1455..1457 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1503..1505 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1521..1532 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1534..1543 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1546..1549 FT /evidence="ECO:0000244|PDB:5IDK" FT HELIX 1551..1554 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1559..1561 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1564..1566 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1568..1572 FT /evidence="ECO:0000244|PDB:5IDK" FT TURN 1573..1576 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1577..1583 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1592..1594 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1596..1600 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1608..1612 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1615..1618 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1623..1627 FT /evidence="ECO:0000244|PDB:5IDK" FT HELIX 1633..1635 FT /evidence="ECO:0000244|PDB:2FP7" FT STRAND 1639..1641 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1647..1650 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1654..1656 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1662..1665 FT /evidence="ECO:0000244|PDB:5IDK" FT STRAND 1672..1674 FT /evidence="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 //