ID POLG_DEN4T Reviewed; 3387 AA. AC Q2YHF0; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2005, sequence version 1. DT 12-AUG-2020, entry version 126. DE RecName: Full=Genome polyprotein; 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=Peptide 2k; 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=Non-structural protein 5; OS Dengue virus type 4 (strain Thailand/0348/1991) (DENV-4). OC Viruses; Riboviria; Flaviviridae; Flavivirus. OX NCBI_TaxID=408688; OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti). OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta). OH NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito). OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=15476884; DOI=10.1016/j.virol.2004.08.003; RA Klungthong C., Zhang C., Mammen M.P. Jr., Ubol S., Holmes E.C.; RT "The molecular epidemiology of dengue virus serotype 4 in Bangkok, RT Thailand."; RL Virology 329:168-179(2004). RN [2] RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 1646-2092. RX PubMed=19008861; DOI=10.1038/emboj.2008.232; RA Luo D., Xu T., Watson R.P., Scherer-Becker D., Sampath A., Jahnke W., RA Yeong S.S., Wang C.H., Lim S.P., Strongin A., Vasudevan S.G., Lescar J.; RT "Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 RT protein."; RL EMBO J. 27:3209-3219(2008). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1393-2092, AND TOPOLOGY RP (NON-STRUCTURAL PROTEIN 2B). RX PubMed=20375022; DOI=10.1074/jbc.m109.090936; RA Luo D., Wei N., Doan D.N., Paradkar P.N., Chong Y., Davidson A.D., RA Kotaka M., Lescar J., Vasudevan S.G.; RT "Flexibility between the protease and helicase domains of the dengue virus RT NS3 protein conferred by the linker region and its functional RT implications."; RL J. Biol. Chem. 285:18817-18827(2010). 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. During virus entry, may CC induce genome penetration into the host cytoplasm after hemifusion CC induced by the surface proteins. Can migrate to the cell nucleus where CC it modulates host functions. Overcomes the anti-viral effects of host CC EXOC1 by sequestering and degrading the latter through the proteasome CC degradation pathway. {ECO:0000250|UniProtKB:P17763}. 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. Envelope protein CC is synthesized in the endoplasmic reticulum in the form of heterodimer CC with protein prM. They play a role in virion budding in the ER, and the CC newly formed immature particle is covered with 60 spikes composed of CC heterodimer between precursor prM and envelope protein E. The virion is CC transported to the Golgi apparatus where the low pH causes dissociation CC of PrM-E heterodimers and formation of E homodimers. 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: [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 1]: Disrupts the host endothelial CC glycocalyx layer of host pulmonary microvascular endothelial cells, CC inducing degradation of sialic acid and shedding of heparan sulfate CC proteoglycans. NS1 induces expression of sialidases, heparanase, and CC activates cathepsin L, which activates heparanase via enzymatic CC cleavage. These effects are probably linked to the endothelial CC hyperpermeability observed in severe dengue disease. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA CC replication complex that functions in virion assembly and antagonizes CC the host immune response. {ECO:0000250|UniProtKB:P17763}. 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. Plays a role in the inhibition of the host innate CC immune response. Interacts with host MAVS and thereby prevents the CC interaction between DDX58 and MAVS. In turn, IFN-beta production is CC impaired. {ECO:0000250|UniProtKB:P17763, 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. 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. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O CC positions. Besides its role in RNA genome replication, also prevents CC the establishment of cellular antiviral state by blocking the CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host CC TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK- CC STAT signaling pathway (By similarity). May reduce immune responses by CC preventing the recruitment of the host PAF1 complex to interferon- CC responsive genes (By similarity). {ECO:0000250|UniProtKB:P09866, CC ECO:0000250|UniProtKB:P17763}. CC -!- CATALYTIC ACTIVITY: [Serine protease NS3]: 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: [RNA-directed RNA polymerase NS5]: 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 -!- 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. Interacts (via N-terminus) with CC host EXOC1 (via C-terminus); this interaction results in EXOC1 CC degradation through the proteasome degradation pathway. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in CC the endoplasmic reticulum and Golgi. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum CC and Golgi. Interacts with protein prM. Interacts with non-structural CC protein 1. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when CC secreted. Interacts with envelope protein E. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with CC serine protease NS3. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with CC serine protease NS3. May form homooligomers. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B. CC Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA CC polymerase NS5; this interaction stimulates RNA-directed RNA polymerase CC NS5 guanylyltransferase activity. Interacts with host SHFL. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with host MAVS; this CC interaction inhibits the synthesis of IFN-beta. Interacts with host CC SHFL. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease CC NS3. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer. Interacts with CC host STAT2; this interaction inhibits the phosphorylation of the CC latter, and, when all viral proteins are present (polyprotein), targets CC STAT2 for degradation. Interacts with serine protease NS3 (By CC similarity). Interacts with host PAF1 complex; the interaction may CC prevent the recruitment of the PAF1 complex to interferon-responsive CC genes, and thus reduces the immune response (By similarity). CC {ECO:0000250|UniProtKB:P09866, ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion CC {ECO:0000250|UniProtKB:P17763}. Host nucleus CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. Host endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. Host endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. 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:P17763}; 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:P17763}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P17763}. Host mitochondrion CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles CC hosting the replication complex. Interacts with host MAVS in the CC mitochondrion-associated endoplasmic reticulum membranes. 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. Host nucleus {ECO:0000250|UniProtKB:P09866, CC ECO:0000250|UniProtKB:P17763}. 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, especially in the DENV 2, 3, 4 CC serotypes. {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 -!- 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]: N-glycosylated. CC {ECO:0000250|UniProtKB:P17763}. 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]: Sumoylation of RNA-directed RNA CC polymerase NS5 increases NS5 protein stability allowing proper viral CC RNA replication. {ECO:0000250|UniProtKB:P29990}. 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 -!- WEB RESOURCE: Name=Virus Pathogen Resource; CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue"; 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; AY618990; AAU89377.1; -; Genomic_RNA. DR PDB; 2JLQ; X-ray; 1.67 A; A=1646-2092. DR PDB; 2JLR; X-ray; 2.00 A; A=1646-2092. DR PDB; 2JLS; X-ray; 2.23 A; A=1646-2092. DR PDB; 2JLU; X-ray; 2.04 A; A/B=1646-2092. DR PDB; 2JLV; X-ray; 2.30 A; A/B=1646-2092. DR PDB; 2JLW; X-ray; 2.60 A; A/B=1646-2092. DR PDB; 2JLX; X-ray; 2.20 A; A/B=1646-2092. DR PDB; 2JLY; X-ray; 2.40 A; A/B=1646-2092. DR PDB; 2JLZ; X-ray; 2.20 A; A/B=1646-2092. DR PDB; 2WHX; X-ray; 2.20 A; A=1475-2092, C=1393-1406. DR PDB; 2WZQ; X-ray; 2.80 A; A=1475-2092, C=1393-1410. DR PDB; 3UYP; X-ray; 2.00 A; B=575-679. DR PDB; 5YVV; X-ray; 3.10 A; A=1393-1439, B=1494-2092. DR PDB; 5YVW; X-ray; 3.10 A; A=1393-1439, B=1494-2092. DR PDBsum; 2JLQ; -. DR PDBsum; 2JLR; -. DR PDBsum; 2JLS; -. DR PDBsum; 2JLU; -. DR PDBsum; 2JLV; -. DR PDBsum; 2JLW; -. DR PDBsum; 2JLX; -. DR PDBsum; 2JLY; -. DR PDBsum; 2JLZ; -. DR PDBsum; 2WHX; -. DR PDBsum; 2WZQ; -. DR PDBsum; 3UYP; -. DR PDBsum; 5YVV; -. DR PDBsum; 5YVW; -. DR SMR; Q2YHF0; -. DR MEROPS; S07.001; -. DR PRIDE; Q2YHF0; -. DR ABCD; Q2YHF0; 1 sequenced antibody. DR BRENDA; 3.4.21.91; 9641. DR EvolutionaryTrace; Q2YHF0; -. DR PRO; PR:Q2YHF0; -. DR Proteomes; UP000000273; Genome. 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:0033650; C:host cell mitochondrion; 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:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW. 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:0003725; F:double-stranded RNA binding; IEA:InterPro. DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW. 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; IEA:UniProtKB-EC. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC. 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; IEA:UniProtKB-KW. 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:0030683; P:mitigation of host immune response by virus; IMP:CACAO. DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW. DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW. DR GO; GO:0039545; P:suppression by virus of host MAVS 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; DP01931; -. DR Gene3D; 1.10.10.930; -; 1. DR Gene3D; 1.10.8.970; -; 1. DR Gene3D; 1.20.1280.260; -; 1. DR Gene3D; 2.40.10.10; -; 1. DR Gene3D; 2.60.260.50; -; 1. DR Gene3D; 2.60.40.350; -; 1. DR Gene3D; 2.60.98.10; -; 1. DR Gene3D; 3.30.387.10; -; 1. DR Gene3D; 3.30.67.10; -; 1. DR InterPro; IPR011492; DEAD_Flavivir. DR InterPro; IPR043502; DNA/RNA_pol_sf. DR InterPro; IPR000069; Env_glycoprot_M_flavivir. DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir. DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1. 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; IPR013756; GlyE_cen_dom_subdom2. 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; IPR043504; Peptidase_S1_PA_chymotrypsin. 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; SSF56672; SSF56672; 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; KW Host mitochondrion; 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 MAVS by virus; Inhibition of host RLR pathway by virus; KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus; KW Ion channel; Ion transport; Membrane; Metal-binding; Methyltransferase; KW mRNA capping; 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; Transmembrane helix; KW Transport; Ubl conjugation; Viral attachment to host cell; KW Viral envelope protein; Viral immunoevasion; Viral ion channel; KW Viral penetration into host cytoplasm; Viral RNA replication; Virion; KW Virus endocytosis by host; Virus entry into host cell; Zinc. FT CHAIN 1..3387 FT /note="Genome polyprotein" FT /id="PRO_0000405229" FT CHAIN 1..99 FT /note="Capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268131" FT PROPEP 100..113 FT /note="ER anchor for the capsid protein C, removed in FT mature form by serine protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268132" FT CHAIN 114..279 FT /note="Protein prM" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268133" FT CHAIN 114..204 FT /note="Peptide pr" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268134" FT CHAIN 205..279 FT /note="Small envelope protein M" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268135" FT CHAIN 280..774 FT /note="Envelope protein E" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268136" FT CHAIN 775..1126 FT /note="Non-structural protein 1" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268137" FT CHAIN 1127..1344 FT /note="Non-structural protein 2A" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268138" FT CHAIN 1345..1474 FT /note="Serine protease subunit NS2B" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268139" FT CHAIN 1475..2092 FT /note="Serine protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268140" FT CHAIN 2093..2219 FT /note="Non-structural protein 4A" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268141" FT PEPTIDE 2220..2242 FT /note="Peptide 2k" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268142" FT CHAIN 2243..2487 FT /note="Non-structural protein 4B" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268143" FT CHAIN 2488..3387 FT /note="RNA-directed RNA polymerase NS5" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000268144" FT TOPO_DOM 1..100 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 101..117 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 118..237 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 238..258 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 259..265 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 266..279 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 280..725 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 726..746 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 747..753 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 754..774 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 775..1194 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1195..1218 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1219..1224 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1225..1243 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1244..1267 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1268..1288 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1289 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1290..1308 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1309..1316 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1317..1337 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1338..1345 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1346..1366 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:20375022" FT TOPO_DOM 1367..1369 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:20375022" FT TRANSMEM 1370..1390 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:20375022" FT TOPO_DOM 1391..1437 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:20375022" FT INTRAMEM 1438..1458 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:20375022" FT TOPO_DOM 1459..2143 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2144..2164 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2165..2169 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2170..2190 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2191 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2192..2212 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2213..2225 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2226..2246 FT /note="Helical; Note=Signal for NS4B" FT /evidence="ECO:0000255" FT TOPO_DOM 2247..2270 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2271..2291 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2292..2301 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2302..2322 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2323..2343 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2344..2364 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2365..2409 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2410..2430 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2431..2455 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2456..2476 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2477..3387 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 1475..1652 FT /note="Peptidase S7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT DOMAIN 1654..1810 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 1820..1987 FT /note="Helicase C-terminal" FT DOMAIN 2489..2751 FT /note="mRNA cap 0-1 NS5-type MT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT DOMAIN 3016..3166 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT NP_BIND 1667..1674 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT REGION 36..71 FT /note="Hydrophobic; homodimerization of capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT REGION 377..390 FT /note="Fusion peptide" FT /evidence="ECO:0000250|UniProtKB:P14336" FT REGION 1397..1436 FT /note="Interacts with and activates NS3 protease" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859" FT REGION 1658..1661 FT /note="Important for RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P14340" FT MOTIF 1758..1761 FT /note="DEAH box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOTIF 2564..2567 FT /note="SUMO-interacting motif" FT /evidence="ECO:0000250|UniProtKB:P29990" FT ACT_SITE 1525 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1549 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1609 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 2548 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2633 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2668 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2704 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2925 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2929 FT /note="Zinc 1; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2934 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2937 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3200 FT /note="Zinc 2; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3216 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3335 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT BINDING 2543 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2573 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2574 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2591 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2592 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2618 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2619 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2634 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2706 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 99..100 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 113..114 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 204..205 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255" FT SITE 279..280 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 774..775 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1126..1127 FT /note="Cleavage; by host" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1344..1345 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1474..1475 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1931 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 1934 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 2092..2093 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2219..2220 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2242..2243 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2487..2488 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2501 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2504 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2505 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2507 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2512 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2516 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2548 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2633 FT /note="Essential for 2'-O-methyltransferase and N-7 FT methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2637 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2668 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2699 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2701 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2704 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT MOD_RES 2543 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P03314" FT CARBOHYD 182 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 346 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 432 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 904 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 981 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2297 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2301 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2453 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 282..309 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 339..400 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 353..384 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 371..395 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 464..564 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 581..612 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 778..789 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 829..917 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 953..997 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1054..1103 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1065..1087 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1086..1090 FT /evidence="ECO:0000250|UniProtKB:P17763" FT STRAND 585..589 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 599..605 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 607..609 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 611..613 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 616..619 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 625..630 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 632..634 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 639..642 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 644..649 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 652..661 FT /evidence="ECO:0000244|PDB:3UYP" FT HELIX 662..664 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 665..672 FT /evidence="ECO:0000244|PDB:3UYP" FT STRAND 1395..1401 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1409..1412 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1417..1420 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1424..1427 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1496..1502 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1507..1514 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1516..1518 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1520..1522 FT /evidence="ECO:0000244|PDB:2WHX" FT HELIX 1524..1527 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1532..1536 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1541..1545 FT /evidence="ECO:0000244|PDB:2WHX" FT TURN 1546..1549 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1550..1556 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1565..1567 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1569..1573 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1581..1585 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1589..1591 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1598..1600 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1612..1614 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1616..1618 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1620..1623 FT /evidence="ECO:0000244|PDB:2WHX" FT STRAND 1631..1634 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 1637..1640 FT /evidence="ECO:0000244|PDB:2WZQ" FT STRAND 1645..1647 FT /evidence="ECO:0000244|PDB:2JLX" FT HELIX 1654..1657 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1662..1665 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1669..1671 FT /evidence="ECO:0000244|PDB:2WZQ" FT TURN 1673..1676 FT /evidence="ECO:0000244|PDB:2JLV" FT HELIX 1677..1687 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1692..1698 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1699..1708 FT /evidence="ECO:0000244|PDB:2JLQ" FT TURN 1709..1711 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1714..1716 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1727..1729 FT /evidence="ECO:0000244|PDB:2JLR" FT STRAND 1731..1735 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1736..1745 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1753..1758 FT /evidence="ECO:0000244|PDB:2JLQ" FT TURN 1759..1761 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1765..1779 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1784..1788 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1806..1810 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1819..1821 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1823..1827 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1832..1835 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1839..1850 FT /evidence="ECO:0000244|PDB:2JLQ" FT TURN 1851..1853 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1856..1859 FT /evidence="ECO:0000244|PDB:2JLQ" FT TURN 1861..1863 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1864..1867 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1868..1872 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1877..1881 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1883..1886 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1894..1898 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1901..1908 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1910..1912 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1914..1922 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1925..1932 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1935..1938 FT /evidence="ECO:0000244|PDB:2WZQ" FT STRAND 1944..1948 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 1960..1969 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 1975..1977 FT /evidence="ECO:0000244|PDB:5YVV" FT HELIX 1984..1989 FT /evidence="ECO:0000244|PDB:2JLQ" FT TURN 1994..1997 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 2001..2012 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 2018..2026 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 2035..2037 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 2042..2044 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 2047..2052 FT /evidence="ECO:0000244|PDB:2JLS" FT STRAND 2054..2056 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 2058..2060 FT /evidence="ECO:0000244|PDB:5YVV" FT STRAND 2062..2064 FT /evidence="ECO:0000244|PDB:2JLQ" FT HELIX 2072..2074 FT /evidence="ECO:0000244|PDB:2JLQ" FT STRAND 2075..2077 FT /evidence="ECO:0000244|PDB:5YVV" FT HELIX 2078..2088 FT /evidence="ECO:0000244|PDB:2JLQ" SQ SEQUENCE 3387 AA; 378438 MW; 1FEDC2D663A0F945 CRC64; MNQRKKVARP PFNMLKRERN RVSTPQGLVK RFSTGLFSGK GPLRMVLAFI TFLRVLSIPP TAGILKRWGQ LKKNKAIKIL TGFRKEIGRM LNILNGRKRS TITLLCLIPT VMAFHLSTRD GEPLMIVAKH ERGRPLLFKT TEGINKCTLI AMDLGEMCED TVTYKCPLLV NTEPEDIDCW CNLTSAWVMY GTCTQSGERR REKRSVALTP HSGMGLETRA ETWMSSEGAW KHAQRVESWI LRNPGFALLA GFMAYMIGQT GIQRTVFFIL MMLVAPSYGM RCVGVGNRDF VEGVSGGAWV DLVLEHGGCV TTMAQGKPTL DFELIKTTAK EVALLRTYCI EASISNITTA TRCPTQGEPY LKEEQDQQYI CRRDMVDRGW GNGCGLFGKG GVVTCAKFSC SGKITGNLVQ IENLEYTVVV TVHNGDTHAV GNDTSNHGVT ATITPRSPSV EVKLPDYGEL TLDCEPRSGI DFNEMILMKM KTKTWLVHKQ WFLDLPLPWT AGADTLEVHW NHKERMVTFK VPHAKRQDVT VLGSQEGAMH SALAGATEVD SGDGNHMFAG HLKCKVRMEK LRIKGMSYTM CSGKFSIDKE MAETQHGTTV VKVKYEGTGA PCKVPIEIRD VNKEKVVGRI ISSTPFAENT NSVTNIELEP PFGDSYIVIG VGDSALTLHW FRKGSSIGKM FESTYRGAKR MAILGETAWD FGSVGGLLTS LGKAVHQVFG SVYTTMFGGV SWMVRILIGL LVLWIGTNSR NTSMAMSCIA VGGITLFLGF TVHADMGCAV SWSGKELKCG SGIFVIDNVH TWTEQYKFQP ESPARLASAI LNAHKDGVCG IRSTTRLENV MWKQITNELN YVLWEGGHDL TVVAGDVKGV LSKGKRALAP PVNDLKYSWK TWGKAKIFTP ETRNSTFLVD GPDTSECPNE RRAWNFLEVE DYGFGMFTTN IWMKFREGSS EVCDHRLMSA AIKDQKAVHA DMGYWIESSK NQTWQIEKAS LIEVKTCLWP KTHTLWSNGV LESQMLIPKA YAGPISQHNY RQGYATQTVG PWHLGKLEID FGECPGTTVT IQEDCDHRGP SLRTTTASGK LVTQWCCRSC TMPPLRFLGE DGCWYGMEIR PLNEKEENMV KSQVSAGQGT SETFSMGLLC LTLFVEECLR RRVTRKHMIL VVVTTLCAII LGGLTWMDLL RALIMLGDTM SGRMGGQIHL AIMAVFKMSP GYVLGIFLRK LTSRETALMV IGMAMTTVLS IPHDLMEFID GISLGLILLK MVTHFDNTQV GTLALSLTFI KSTMPLVMAW RTIMAVLFVV TLIPLCRTSC LQKQSHWVEI TALILGAQAL PVYLMTLMKG ASKRSWPLNE GIMAVGLVSL LGSALLKNDV PLAGPMVAGG LLLAAYVMSG SSADLSLEKA ANVQWDEMAD ITGSSPIIEV KQDEDGSFSI RDVEETNMIT LLVKLALITV SGLYPLAIPV TMTLWYMWQV KTQRSGALWD VPSPAAAQKA TLTEGVYRIM QRGLFGKTQV GVGIHMEGVF HTMWHVTRGS VICHESGRLE PSWADVRNDM ISYGGGWRLG DKWDKEEDVQ VLAIEPGKNP KHVQTKPGLF KTLTGEIGAV TLDFKPGTSG SPIINRKGKV IGLYGNGVVT KSGDYVSAIT QAERIGEPDY EVDEDIFRKK RLTIMDLHPG AGKTKRILPS IVREALKRRL RTLILAPTRV VAAEMEEALR GLPIRYQTPA VKSEHTGREI VDLMCHATFT TRLLSSTRVP NYNLIVMDEA HFTDPSSVAA RGYISTRVEM GEAAAIFMTA TPPGTTDPFP QSNSPIEDIE REIPERSWNT GFDWITDYQG KTVWFVPSIK AGNDIANCLR KSGKKVIQLS RKTFDTEYPK TKLTDWDFVV TTDISEMGAN FRAGRVIDPR RCLKPVILTD GPERVILAGP IPVTPASAAQ RRGRIGRNPA QEDDQYVFSG DPLRNDEDHA HWTEAKMLLD NIYTPEGIIP TLFGPEREKT QAIDGEFRLR GEQRKTFVEL MRRGDLPVWL SYKVASAGIS YKDREWCFTG ERNNQILEEN MEVEIWTREG EKKKLRPKWL DARVYADPMA LKDFKEFASG RKSITLDILT EIASLPTYLS SRAKLALDNI VMLHTTERGG KAYQHALNEL PESLETLMLV ALLGAMTAGI FLFFMQGKGI GKLSMGLIAI AVASGLLWVA EIQPQWIAAS IILEFFLMVL LVPEPEKQRT PQDNQLIYVI LTILTIIALV AANEMGLIEK TKTDFGFYQA KTETTILDVD LRPASAWTLY AVATTILTPM LRHTIENTSA NLSLAAIANQ AAVLMGLGKG WPLHRMDLGV PLLAMGCYSQ VNPTTLTASL VMLLVHYAII GPGLQAKATR EAQKRTAAGI MKNPTVDGIT VIDLEPISYD PKFEKQLGQV MLLVLCAGQL LLMRTTWAFC EVLTLATGPI LTLWEGNPGR FWNTTIAVST ANIFRGSYLA GAGLAFSLIK NAQTPRRGTG TTGETLGEKW KRQLNSLDRK EFEEYKRSGI LEVDRTEAKS ALKDGSKIKY AVSRGTSKIR WIVERGMVKP KGKVVDLGCG RGGWSYYMAT LKNVTEVKGY TKGGPGHEEP IPMATYGWNL VKLHSGVDVF YKPTEQVDTL LCDIGESSSN PTIEEGRTLR VLKMVEPWLS SKPEFCIKVL NPYMPTVIEE LEKLQRKHGG SLVRCPLSRN STHEMYWVSG VSGNIVSSVN TTSKMLLNRF TTRHRKPTYE KDADLGAGTR SVSTETEKPD MTIIGRRLQR LQEEHKETWH YDHENPYRTW AYHGSYEAPS TGSASSMVNG VVKLLTKPWD VVPMVTQLAM TDTTPFGQQR VFKEKVDTRT PQPKPGTRVV MTTTANWLWA LLGRKKNPRL CTREEFISKV RSNAAIGAVF QEEQGWTSAS EAVNDSRFWE LVDKERALHQ EGKCESCVYN MMGKREKKLG EFGRAKGSRA IWYMWLGARF LEFEALGFLN EDHWFGRENS WSGVEGEGLH RLGYILEDID KKDGDLIYAD DTAGWDTRIT EDDLLNEELI TEQMAPHHKI LAKAIFKLTY QNKVVKVLRP TPKGAVMDII SRKDQRGSGQ VGTYGLNTFT NMEVQLIRQM EAEGVITRDD MHNPKGLKER VEKWLKECGV DRLKRMAISG DDCVVKPLDE RFSTSLLFLN DMGKVRKDIP QWEPSKGWKN WQEVPFCSHH FHKIFMKDGR SLVVPCRNQD ELIGRARISQ GAGWSLRETA CLGKAYAQMW SLMYFHRRDL RLASMAICSA VPTEWFPTSR TTWSIHAHHQ WMTTEDMLKV WNRVWIEDNP NMIDKTPVHS WEDIPYLGKR EDLWCGSLIG LSSRATWAKN IQTAITQVRN LIGKEEYVDY MPVMKRYSAH FESEGVL //