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   11-JUL-2012, entry version 134.
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=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;
DE              EC=3.6.4.13;
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;
DE              EC=2.1.1.57;
DE              EC=2.7.7.48;
DE     AltName: Full=NS5;
OS   West Nile virus (WNV).
OC   Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae;
OC   Flavivirus; Japanese encephalitis virus group.
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   MEDLINE=86124703; 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   MEDLINE=21176376; 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   MEDLINE=85274372; 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   MEDLINE=86072082; 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   DISULFIDE BONDS IN ENVELOPE PROTEIN E.
RX   MEDLINE=87122143; 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   [6]
RP   FUNCTION OF 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   [7]
RP   FUNCTION OF NON-STRUCTURAL PROTEIN 4B.
RX   PubMed=15956546; DOI=10.1128/JVI.79.13.8004-8013.2005;
RA   Munoz-Jordan J.L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L.,
RA   Ashok M., Lipkin W.I., Garcia-Sastre A.;
RT   "Inhibition of alpha/beta interferon signaling by the NS4B protein of
RT   flaviviruses.";
RL   J. Virol. 79:8004-8013(2005).
RN   [8]
RP   SUBCELLULAR LOCATION OF SERINE PROTEASE NS3, AND SUBCELLULAR LOCATION
RP   OF 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 AS METHYLTRANSFERASE, AND MUTAGENESIS OF LYS-2586; ASP-2671;
RP   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 OF 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   FUNCTION OF RNA-DIRECTED RNA POLYMERASE NS5.
RC   STRAIN=NY1999;
RX   PubMed=20106931; DOI=10.1128/JVI.01161-09;
RA   Laurent-Rolle M., Boer E.F., Lubick K.J., Wolfinbarger J.B.,
RA   Carmody A.B., Rockx B., Liu W., Ashour J., Shupert W.L.,
RA   Holbrook M.R., Barrett A.D., Mason P.W., Bloom M.E., Garcia-Sastre A.,
RA   Khromykh A.A., Best S.M.;
RT   "The NS5 protein of the virulent West Nile virus NY99 strain is a
RT   potent antagonist of type I interferon-mediated JAK-STAT signaling.";
RL   J. Virol. 84:3503-3515(2010).
RN   [12]
RP   FUNCTION OF RNA-DIRECTED RNA POLYMERASE NS5.
RC   STRAIN=NY1999;
RX   PubMed=19850911; DOI=10.1261/rna.1609709;
RA   Issur M., Geiss B.J., Bougie I., Picard-Jean F., Despins S.,
RA   Mayette J., Hobdey S.E., Bisaillon M.;
RT   "The flavivirus NS5 protein is a true RNA guanylyltransferase that
RT   catalyzes a two-step reaction to form the RNA cap structure.";
RL   RNA 15:2340-2350(2009).
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 self-assembles to form an icosahedral
CC       capsid about 30 nm in diameter. The capsid encapsulates the
CC       genomic RNA (By similarity).
CC   -!- FUNCTION: prM acts as a chaperone for envelope protein E during
CC       intracellular virion assembly by masking and inactivating envelope
CC       protein E fusion peptide. prM is matured in the last step of
CC       virion assembly, presumably to avoid catastrophic activation of
CC       the viral fusion peptide induced by the acidic pH of the trans-
CC       Golgi network. After cleavage by host furin, the pr peptide is
CC       released in the extracellular medium and small envelope protein M
CC       and envelope protein E homodimers are dissociated (By similarity).
CC   -!- FUNCTION: Envelope protein E binding to host cell surface receptor
CC       is followed by virus internalization through clathrin-mediated
CC       endocytosis. Envelope protein E is subsequently involved in
CC       membrane fusion between virion and host late endosomes.
CC       Synthesized as an homodimer with prM which acts as a chaperone for
CC       envelope protein E. After cleavage of prM, envelope protein E
CC       dissociate from small envelope protein M and homodimerizes (By
CC       similarity).
CC   -!- FUNCTION: Non-structural protein 1 is involved in virus
CC       replication and regulation of the innate immune response (By
CC       similarity).
CC   -!- FUNCTION: Non-structural protein 2A may be involved viral RNA
CC       replication and capsid assembly (Potential).
CC   -!- FUNCTION: Non-structural protein 2B is a required cofactor for the
CC       serine protease function of NS3 (By similarity).
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,
CC       NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds
CC       RNA and unwinds dsRNA in the 3' to 5' direction (By similarity).
CC   -!- FUNCTION: Non-structural protein 4A induces host endoplasmic
CC       reticulum membrane rearrangements leading to the formation of
CC       virus-induced membranous vesicles hosting the dsRNA and
CC       polymerase, functionning as a replication complex. NS4A might also
CC       regulate the ATPase activity of the NS3 helicase (By similarity).
CC   -!- FUNCTION: Peptide 2k functions as a signal peptide for NS4B and is
CC       required for the interferon antagonism activity of the latter (By
CC       similarity).
CC   -!- FUNCTION: Non-structural protein 4B inhibits interferon (IFN)-
CC       induced host STAT1 phosphorylation and nuclear translocation,
CC       thereby preventing the establishment of cellular antiviral state
CC       by blocking the IFN-alpha/beta pathway (By similarity).
CC   -!- FUNCTION: RNA-directed RNA polymerase NS5 replicates the viral (+)
CC       and (-) genome, and performs the capping of genomes in the
CC       cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose
CC       2'-O positions. Besides its role in genome replication, also
CC       prevents the establishment of cellular antiviral state by blocking
CC       the interferon-alpha/beta (IFN-alpha/beta) signaling pathway.
CC       Inhibits host JAK1 and TYK2 phosphorylation, thereby preventing
CC       activation of JAK-STAT signaling pathway (By similarity).
CC   -!- CATALYTIC ACTIVITY: Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds
CC       in which each of the Xaa can be either Arg or Lys and Yaa can be
CC       either Ser or Ala.
CC   -!- CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate
CC       + RNA(n+1).
CC   -!- CATALYTIC ACTIVITY: NTP + H(2)O = NDP + phosphate.
CC   -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC   -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + G(5')pppR-RNA = S-
CC       adenosyl-L-homocysteine + m(7)G(5')pppR-RNA.
CC   -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + m(7)G(5')pppR-RNA =
CC       S-adenosyl-L-homocysteine + m(7)G(5')pppRm-RNA.
CC   -!- SUBUNIT: Capsid protein C forms homodimers. prM and envelope
CC       protein E form heterodimers in the endoplasmic reticulum and
CC       Golgi. In immature particles, there are 60 icosaedrally organized
CC       trimeric spikes on the surface. Each spike consists of three
CC       heterodimers of envelope protein M precursor (prM) and envelope
CC       protein E. NS1 forms homodimers as well as homohexamers when
CC       secreted. NS1 may interact with NS4A. NS3 and NS2B form a
CC       heterodimer. NS3 is the catalytic subunit, whereas NS2B strongly
CC       stimulates the latter, acting as a cofactor. In the absence of the
CC       NS2B, NS3 protease is unfolded and inactive. NS3 interacts with
CC       unphosphorylated NS5; this interaction stimulates NS5
CC       guanylyltransferase activity (By similarity).
CC   -!- INTERACTION:
CC       Q17NZ6:AaeL_AAEL000563 (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 (Potential). Host
CC       membrane; Single-pass membrane protein (Potential).
CC   -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane;
CC       Multi-pass membrane protein (By similarity). Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein (By similarity).
CC   -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane; Multi-
CC       pass membrane protein (By similarity). Host endoplasmic reticulum
CC       membrane; Multi-pass membrane protein (By similarity).
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted. Host
CC       endoplasmic reticulum membrane; Peripheral membrane protein;
CC       Lumenal side (By similarity).
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein (Potential).
CC   -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host
CC       endoplasmic reticulum membrane; Multi-pass membrane protein
CC       (Potential).
CC   -!- SUBCELLULAR LOCATION: Serine protease NS3: Host endoplasmic
CC       reticulum membrane; Peripheral membrane protein; Cytoplasmic side
CC       (By similarity). Note=Remains non-covalently associated to NS3
CC       protease (By similarity).
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 4A: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein (By similarity).
CC       Note=Located in RE-associated vesicles hosting the replication
CC       complex.
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein (By similarity).
CC   -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host
CC       endoplasmic reticulum membrane; Peripheral membrane protein;
CC       Cytoplasmic side (By similarity). Host nucleus. Note=Located in
CC       RE-associated vesicles hosting the replication complex.
CC   -!- PTM: Specific enzymatic cleavages in vivo by the viral protease
CC       NS3 and host cell enzymes yield mature proteins. The nascent
CC       protein C contains a C-terminal hydrophobic domain that act as a
CC       signal sequence for translocation of prM into the lumen of the ER.
CC       Mature soluble protein C is released after cleavage by NS3
CC       protease at a site upstream of this hydrophobic domain. prM is
CC       cleaved in post-Golgi vesicles by a host furin, releasing the
CC       mature small envelope protein M, and peptide pr. Peptide 2K acts
CC       as a signal sequence and is removed from the N-terminus of NS4B by
CC       the host signal peptidase in the ER lumen. Signal cleavage at the
CC       2K-4B site requires a prior NS3 protease-mediated cleavage at the
CC       4A-2K site (By similarity).
CC   -!- PTM: RNA-directed RNA polymerase NS5 is phosphorylated on serines
CC       residues. This phosphorylation may trigger NS5 nuclear
CC       localization (By similarity).
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.
CC   -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC   -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC   -!- SIMILARITY: Contains 1 mRNA cap 0-1 NS5-type MT domain.
CC   -!- SIMILARITY: Contains 1 peptidase S7 domain.
CC   -!- SIMILARITY: Contains 1 RdRp catalytic domain.
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=1419-1463, B=1503-1679.
DR   PDB; 2IJO; X-ray; 2.30 A; A=1419-1465, B=1502-1685.
DR   PDB; 2P5P; X-ray; 2.80 A; A/B/C=585-701.
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   PDBsum; 2FP7; -.
DR   PDBsum; 2G05; -.
DR   PDBsum; 2G2G; -.
DR   PDBsum; 2GGV; -.
DR   PDBsum; 2IJO; -.
DR   PDBsum; 2P5P; -.
DR   PDBsum; 3E90; -.
DR   PDBsum; 3I50; -.
DR   ProteinModelPortal; P06935; -.
DR   SMR; P06935; 25-97, 291-689, 1420-1458, 1502-2120, 2531-2792, 2799-3424.
DR   IntAct; P06935; 3.
DR   MEROPS; S07.001; -.
DR   BindingDB; P06935; -.
DR   EvolutionaryTrace; P06935; -.
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:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:InterPro.
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:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:EC.
DR   GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:EC.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0030683; P:evasion by virus of host immune response; IEA:UniProtKB-KW.
DR   GO; GO:0006370; P:mRNA capping; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR   Gene3D; G3DSA:3.30.67.10; Flav_glyE_cen_2; 1.
DR   Gene3D; G3DSA:2.60.98.10; Flav_glyE_dim; 3.
DR   Gene3D; G3DSA:2.60.40.350; Flv_glyE_Ig-like; 1.
DR   InterPro; IPR011492; DEAD_Flavivir.
DR   InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR   InterPro; IPR001122; Flavi_capsidC.
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; IPR001850; Flavivirus_NS3_S7.
DR   InterPro; IPR000336; Flv_glyE_Ig-like.
DR   InterPro; IPR014412; Gen_Poly_FLV.
DR   InterPro; IPR011998; GlycoprotE/E1_cen/dimer.
DR   InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR   InterPro; IPR013754; GlyE_dim.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR009003; Pept_cys/ser_Trypsin-like.
DR   InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR002877; rRNA_MeTrfase_FtsJ_dom.
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; PF00271; Helicase_C; 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; SSF56983; Flavi_glycoprotE; 1.
DR   SUPFAM; SSF81296; Ig_E-set; 1.
DR   SUPFAM; SSF50494; Pept_Ser_Cys; 1.
DR   PROSITE; PS00690; DEAH_ATP_HELICASE; FALSE_NEG.
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 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 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; Transcription; Transcription regulation; Transferase;
KW   Transmembrane; 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.
FT   INIT_MET      1      1       Removed; by host (Potential).
FT   CHAIN         2    105       Capsid protein C.
FT                                /FTId=PRO_0000037743.
FT   PROPEP      106    123       ER anchor for the protein C, removed in
FT                                mature form by serine protease NS3 (By
FT                                similarity).
FT                                /FTId=PRO_0000037744.
FT   CHAIN       124    290       prM.
FT                                /FTId=PRO_0000405150.
FT   CHAIN       124    215       Peptide pr.
FT                                /FTId=PRO_0000405151.
FT   CHAIN       216    290       Small envelope protein M.
FT                                /FTId=PRO_0000037745.
FT   CHAIN       291    787       Envelope protein E.
FT                                /FTId=PRO_0000037746.
FT   CHAIN       788   1139       Non-structural protein 1.
FT                                /FTId=PRO_0000037747.
FT   CHAIN      1140   1370       Non-structural protein 2A.
FT                                /FTId=PRO_0000037748.
FT   CHAIN      1371   1501       Serine protease subunit NS2B.
FT                                /FTId=PRO_0000037749.
FT   CHAIN      1502   2120       Serine protease NS3.
FT                                /FTId=PRO_0000037750.
FT   CHAIN      2121   2246       Non-structural protein 4A.
FT                                /FTId=PRO_0000037751.
FT   PEPTIDE    2247   2269       Peptide 2k (By similarity).
FT                                /FTId=PRO_0000405152.
FT   CHAIN      2270   2525       Non-structural protein 4B.
FT                                /FTId=PRO_0000037752.
FT   CHAIN      2526   3430       RNA-directed RNA polymerase NS5.
FT                                /FTId=PRO_0000037753.
FT   TOPO_DOM      2    105       Cytoplasmic (Potential).
FT   TRANSMEM    106    126       Helical; (Potential).
FT   TOPO_DOM    127    248       Extracellular (Potential).
FT   TRANSMEM    249    269       Helical; (Potential).
FT   TOPO_DOM    270    275       Cytoplasmic (Potential).
FT   TRANSMEM    276    292       Helical; (Potential).
FT   TOPO_DOM    293    739       Extracellular (Potential).
FT   INTRAMEM    740    760       Helical; (Potential).
FT   TOPO_DOM    761    766       Extracellular (Potential).
FT   INTRAMEM    767    787       Helical; (Potential).
FT   TOPO_DOM    788   1138       Extracellular (Potential).
FT   TRANSMEM   1139   1159       Helical; (Potential).
FT   TOPO_DOM   1160   1212       Cytoplasmic (Potential).
FT   TRANSMEM   1213   1233       Helical; (Potential).
FT   TOPO_DOM   1234   1243       Lumenal (Potential).
FT   TRANSMEM   1244   1264       Helical; (Potential).
FT   TOPO_DOM   1265   1292       Cytoplasmic (Potential).
FT   TRANSMEM   1293   1313       Helical; (Potential).
FT   TOPO_DOM   1314   1340       Lumenal (Potential).
FT   TRANSMEM   1341   1361       Helical; (Potential).
FT   TOPO_DOM   1362   1371       Cytoplasmic (Potential).
FT   TRANSMEM   1372   1392       Helical; (Potential).
FT   TOPO_DOM   1393   1395       Lumenal (Potential).
FT   TRANSMEM   1396   1416       Helical; (Potential).
FT   TOPO_DOM   1417   1473       Cytoplasmic (Potential).
FT   INTRAMEM   1474   1494       Helical; (Potential).
FT   TOPO_DOM   1495   2170       Cytoplasmic (Potential).
FT   TRANSMEM   2171   2191       Helical; (Potential).
FT   TOPO_DOM   2192   2196       Lumenal (Potential).
FT   INTRAMEM   2197   2217       Helical; (Potential).
FT   TOPO_DOM   2218   2218       Lumenal (Potential).
FT   TRANSMEM   2219   2239       Helical; (Potential).
FT   TOPO_DOM   2240   2254       Cytoplasmic (Potential).
FT   TRANSMEM   2255   2275       Helical; Note=Signal for NS4B;
FT                                (Potential).
FT   TOPO_DOM   2276   2309       Lumenal (Potential).
FT   INTRAMEM   2310   2330       Helical; (Potential).
FT   TOPO_DOM   2331   2355       Lumenal (Potential).
FT   INTRAMEM   2356   2376       Helical; (Potential).
FT   TOPO_DOM   2377   2377       Lumenal (Potential).
FT   TRANSMEM   2378   2398       Helical; (Potential).
FT   TOPO_DOM   2399   2441       Cytoplasmic (Potential).
FT   TRANSMEM   2442   2462       Helical; (Potential).
FT   TOPO_DOM   2463   2467       Lumenal (Potential).
FT   TRANSMEM   2468   2488       Helical; (Potential).
FT   TOPO_DOM   2489   3430       Cytoplasmic (Potential).
FT   DOMAIN     1502   1679       Peptidase S7.
FT   DOMAIN     1682   1838       Helicase ATP-binding.
FT   DOMAIN     1849   2014       Helicase C-terminal.
FT   DOMAIN     2526   2791       mRNA cap 0-1 NS5-type MT.
FT   DOMAIN     3055   3207       RdRp catalytic.
FT   NP_BIND    1695   1702       ATP (Potential).
FT   REGION       33     74       Hydrophobic; homodimerization of capsid
FT                                protein C (By similarity).
FT   REGION      388    401       Involved in fusion.
FT   REGION     1424   1463       Interacts with and activates NS3 protease
FT                                (By similarity).
FT   MOTIF      1786   1789       DEAH box.
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 (By similarity).
FT   ACT_SITE   1576   1576       Charge relay system; for serine protease
FT                                NS3 activity (By similarity).
FT   ACT_SITE   1636   1636       Charge relay system; for serine protease
FT                                NS3 activity (By similarity).
FT   BINDING    2538   2538       mRNA cap (By similarity).
FT   BINDING    2541   2541       mRNA cap; via carbonyl oxygen (By
FT                                similarity).
FT   BINDING    2542   2542       mRNA cap (By similarity).
FT   BINDING    2544   2544       mRNA cap; via carbonyl oxygen (By
FT                                similarity).
FT   BINDING    2553   2553       mRNA cap (By similarity).
FT   BINDING    2581   2581       S-adenosyl-L-methionine (By similarity).
FT   BINDING    2611   2611       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen (By similarity).
FT   BINDING    2612   2612       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen (By similarity).
FT   BINDING    2629   2629       S-adenosyl-L-methionine (By similarity).
FT   BINDING    2630   2630       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen (By similarity).
FT   BINDING    2656   2656       S-adenosyl-L-methionine (By similarity).
FT   BINDING    2657   2657       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen (By similarity).
FT   BINDING    2675   2675       mRNA cap (By similarity).
FT   BINDING    2738   2738       mRNA cap (By similarity).
FT   BINDING    2740   2740       mRNA cap (By similarity).
FT   BINDING    2745   2745       S-adenosyl-L-methionine (By similarity).
FT   SITE        105    106       Cleavage; by viral protease NS3.
FT   SITE        123    124       Cleavage; by host signal peptidase (By
FT                                similarity).
FT   SITE        215    216       Cleavage; by host furin (Potential).
FT   SITE        290    291       Cleavage; by host signal peptidase
FT                                (Potential).
FT   SITE        787    788       Cleavage; by host signal peptidase
FT                                (Potential).
FT   SITE       1139   1140       Cleavage; by host (Potential).
FT   SITE       1370   1371       Cleavage; by viral protease NS3.
FT   SITE       1501   1502       Cleavage; by autolysis.
FT   SITE       2120   2121       Cleavage; by autolysis.
FT   SITE       2246   2247       Cleavage; by viral protease NS3.
FT   SITE       2269   2270       Cleavage; by host signal peptidase
FT                                (Potential).
FT   SITE       2525   2526       Cleavage; by viral protease NS3.
FT   SITE       2549   2549       mRNA cap binding (By similarity).
FT   SITE       2586   2586       Essential for 2'-O-methyltransferase
FT                                activity.
FT   SITE       2671   2671       Essential for 2'-O-methyltransferase and
FT                                N-7 methyltransferase activity.
FT   SITE       2672   2672       S-adenosyl-L-methionine binding (By
FT                                similarity).
FT   SITE       2707   2707       Essential for 2'-O-methyltransferase
FT                                activity.
FT   SITE       2743   2743       Essential for 2'-O-methyltransferase
FT                                activity.
FT   CARBOHYD    138    138       N-linked (GlcNAc...); by host
FT                                (Potential).
FT   CARBOHYD    917    917       N-linked (GlcNAc...); by host
FT                                (Potential).
FT   CARBOHYD    962    962       N-linked (GlcNAc...); by host
FT                                (Potential).
FT   CARBOHYD    994    994       N-linked (GlcNAc...); by host
FT                                (Potential).
FT   CARBOHYD   2336   2336       N-linked (GlcNAc...); by host
FT                                (Potential).
FT   DISULFID    293    320
FT   DISULFID    350    406
FT   DISULFID    364    395
FT   DISULFID    382    411
FT   DISULFID    476    574
FT   DISULFID    591    622
FT   MUTAGEN    2586   2586       K->A: Complete loss of 2'-O-
FT                                methyltransferase activity. No effect on
FT                                N-7 methyltransferase activity.
FT   MUTAGEN    2671   2671       D->A: Lethal for the virus. Complete loss
FT                                of 2'-O and N-7 methyltransferase
FT                                activies.
FT   MUTAGEN    2707   2707       K->A: Complete loss of 2'-O-
FT                                methyltransferase activity. No effect on
FT                                N-7 methyltransferase activity.
FT   MUTAGEN    2743   2743       E->A: Complete loss of 2'-O-
FT                                methyltransferase activity. No effect on
FT                                N-7 methyltransferase activity.
FT   STRAND      299    303
FT   STRAND      312    314
FT   STRAND      320    324
FT   STRAND      326    328
FT   STRAND      331    342
FT   STRAND      344    363
FT   STRAND      365    367
FT   HELIX       373    376
FT   STRAND      380    389
FT   HELIX       391    393
FT   STRAND      399    412
FT   STRAND      414    419
FT   HELIX       422    424
FT   STRAND      425    431
FT   STRAND      457    459
FT   HELIX       467    469
FT   STRAND      470    475
FT   STRAND      480    482
FT   STRAND      486    491
FT   STRAND      496    500
FT   HELIX       501    504
FT   HELIX       523    525
FT   STRAND      526    528
FT   STRAND      538    540
FT   HELIX       545    549
FT   STRAND      553    555
FT   STRAND      563    566
FT   STRAND      573    577
FT   HELIX       578    580
FT   STRAND      595    603
FT   STRAND      605    607
FT   STRAND      609    615
FT   STRAND      621    623
FT   STRAND      626    631
FT   STRAND      634    637
FT   STRAND      639    643
FT   STRAND      657    662
FT   STRAND      665    673
FT   STRAND      679    685
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
//