ID POLG_DEN27 Reviewed; 3391 AA. AC P29991; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 12-AUG-2020, entry version 178. 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 2 (strain 16681-PDK53) (DENV-2). OC Viruses; Riboviria; Flaviviridae; Flavivirus. OX NCBI_TaxID=31635; OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti). OH NCBI_TaxID=299627; Aedes furcifer (Mosquito). OH NCBI_TaxID=299628; Aedes taylori (Mosquito). OH NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas). OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=1312269; DOI=10.1016/0042-6822(92)90460-7; RA Blok J., McWilliam S.M., Butler H.C., Gibbs A.J., Weiller G., Herring B.L., RA Hemsley A.C., Aaskov J.G., Yoksan S., Bhamarapravati N.; RT "Comparison of a dengue-2 virus and its candidate vaccine derivative: RT sequence relationships with the flaviviruses and other viruses."; RL Virology 187:573-590(1992). RN [2] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 578-674. RX PubMed=18264114; DOI=10.1038/nsmb.1382; RA Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., Battisti A.J., RA Sukupolvi-Petty S., Sedlak D., Fremont D.H., Chipman P.R., Roehrig J.T., RA Diamond M.S., Kuhn R.J., Rossmann M.G.; RT "Binding of a neutralizing antibody to dengue virus alters the arrangement RT of surface glycoproteins."; RL Nat. Struct. Mol. Biol. 15:312-317(2008). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2493-2757. RX PubMed=19101564; DOI=10.1016/j.jmb.2008.11.058; RA Geiss B.J., Thompson A.A., Andrews A.J., Sons R.L., Gari H.H., Keenan S.M., RA Peersen O.B.; RT "Analysis of flavivirus NS5 methyltransferase cap binding."; RL J. Mol. Biol. 385:1643-1654(2009). RN [4] RP FUNCTION (NON-STRUCTURAL PROTEIN 1). RX PubMed=26562291; DOI=10.1371/journal.ppat.1005277; RA Scaturro P., Cortese M., Chatel-Chaix L., Fischl W., Bartenschlager R.; RT "Dengue virus non-structural protein 1 modulates infectious particle RT production via interaction with the structural proteins."; RL PLoS Pathog. 11:E1005277-E1005277(2015). 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:P17763, CC ECO:0000250|UniProtKB:P29990}. 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 -!- 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 (By similarity). May interact with host SRPRA and SEC61G (By CC similarity). {ECO:0000250|UniProtKB:P17763, CC ECO:0000250|UniProtKB:P29990}. 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:P17763, ECO:0000250|UniProtKB:P29990}. CC -!- INTERACTION: CC PRO_0000037940; P26599: PTBP1; Xeno; NbExp=5; IntAct=EBI-8826689, EBI-350540; CC PRO_0000037946; P04114: APOB; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-3926040; CC PRO_0000037946; P61201: COPS2; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-1050386; CC PRO_0000037946; Q92564: DCUN1D4; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-2654610; CC PRO_0000037946; Q03001: DST; Xeno; NbExp=4; IntAct=EBI-8826488, EBI-310758; CC PRO_0000037946; Q08379: GOLGA2; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-618309; CC PRO_0000037946; O75925: PIAS1; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-629434; CC PRO_0000037946; P63279: UBE2I; Xeno; NbExp=3; IntAct=EBI-8826488, EBI-80168; CC PRO_0000308465; Q9ULX6: AKAP8L; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-357530; CC PRO_0000308465; Q9ULJ7: ANKRD50; Xeno; NbExp=4; IntAct=EBI-8826747, EBI-5653671; CC PRO_0000308465; A8MPP1: DDX11L8; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-5463183; CC PRO_0000308465; P17844: DDX5; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-351962; CC PRO_0000308465; P78344: EIF4G2; Xeno; NbExp=4; IntAct=EBI-8826747, EBI-296519; CC PRO_0000308465; A6NCC3: GOLGA8O; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-8827490; CC PRO_0000308465; Q8WUM4: PDCD6IP; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-310624; CC PRO_0000308465; P30041: PRDX6; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-2255129; CC PRO_0000308465; P26599: PTBP1; Xeno; NbExp=3; IntAct=EBI-8826747, EBI-350540; 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:P17763}. CC Note=Located in RE-associated vesicles hosting the replication complex. CC NS5 protein is mainly localized in the nucleus rather than in ER CC vesicles, especially in the DENV 2, 3, 4 serotypes. CC {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; M84728; AAA73186.1; -; Genomic_RNA. DR PIR; B42451; GNWV26. DR PDB; 2R29; X-ray; 3.00 A; A=578-674. DR PDB; 3EVG; X-ray; 2.20 A; A=2493-2757. DR PDB; 6FLA; X-ray; 2.90 A; I=577-677. DR PDBsum; 2R29; -. DR PDBsum; 3EVG; -. DR PDBsum; 6FLA; -. DR SMR; P29991; -. DR IntAct; P29991; 107. DR PRIDE; P29991; -. DR ABCD; P29991; 1 sequenced antibody. DR EvolutionaryTrace; P29991; -. DR PRO; PR:P29991; -. DR Proteomes; UP000008390; 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: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 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..3391 FT /note="Genome polyprotein" FT /id="PRO_0000405214" FT CHAIN 1..100 FT /note="Capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037936" FT PROPEP 101..114 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_0000037937" FT PROPEP 101..114 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_0000441419" FT CHAIN 115..280 FT /note="Protein prM" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000308279" FT CHAIN 115..205 FT /note="Peptide pr" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000308280" FT CHAIN 206..280 FT /note="Small envelope protein M" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037938" FT CHAIN 281..775 FT /note="Envelope protein E" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037939" FT CHAIN 776..1127 FT /note="Non-structural protein 1" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037940" FT CHAIN 1128..1345 FT /note="Non-structural protein 2A" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037941" FT CHAIN 1346..1475 FT /note="Serine protease subunit NS2B" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037943" FT CHAIN 1476..2093 FT /note="Serine protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000308465" FT CHAIN 2094..2220 FT /note="Non-structural protein 4A" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037944" FT PEPTIDE 2221..2243 FT /note="Peptide 2k" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000308281" FT CHAIN 2244..2491 FT /note="Non-structural protein 4B" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037945" FT CHAIN 2492..3391 FT /note="RNA-directed RNA polymerase NS5" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037946" FT TOPO_DOM 1..101 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 102..122 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 123..242 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 243..260 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 261 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 262..280 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 281..727 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 728..748 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 749..752 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 753..773 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 774..1195 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1196..1220 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1221..1226 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1227..1245 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1246..1269 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1270..1290 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1291 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1292..1310 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1311..1317 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1318..1338 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1339..1346 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1347..1367 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1368..1370 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1371..1391 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1392..1447 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 1448..1468 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1469..2147 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2148..2168 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2169..2170 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2171..2191 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2192 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2193..2213 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2214..2228 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2229..2249 FT /note="Helical; Note=Signal for NS4B" FT /evidence="ECO:0000255" FT TOPO_DOM 2250..2274 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2275..2295 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2296..2316 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2317..2337 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2338..2347 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2348..2368 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2369..2413 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2414..2434 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2435..2459 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2460..2480 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2481..3391 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 1476..1653 FT /note="Peptidase S7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT DOMAIN 1655..1811 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 1821..1988 FT /note="Helicase C-terminal" FT DOMAIN 2493..2755 FT /note="mRNA cap 0-1 NS5-type MT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT DOMAIN 3020..3169 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT NP_BIND 1668..1675 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT REGION 1..15 FT /note="Interaction with host EXOC1" FT /evidence="ECO:0000250|UniProtKB:P17763" FT REGION 37..72 FT /note="Hydrophobic; homodimerization of capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT REGION 378..391 FT /note="Fusion peptide" FT /evidence="ECO:0000250|UniProtKB:P14336" FT REGION 1398..1437 FT /note="Interacts with and activates NS3 protease" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859" FT REGION 1659..1662 FT /note="Important for RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P14340" FT MOTIF 1759..1762 FT /note="DEAH box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOTIF 2568..2571 FT /note="SUMO-interacting motif" FT /evidence="ECO:0000250|UniProtKB:P29990" FT COMPBIAS 97..100 FT /note="Poly-Arg" FT COMPBIAS 1434..1437 FT /note="Poly-Glu" FT COMPBIAS 2148..2154 FT /note="Poly-Leu" FT COMPBIAS 3383..3386 FT /note="Poly-Glu" FT ACT_SITE 1526 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1550 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 1610 FT /note="Charge relay system; for serine protease NS3 FT activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT ACT_SITE 2552 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2637 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2672 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2708 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2929 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2933 FT /note="Zinc 1; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2938 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 2941 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3203 FT /note="Zinc 2; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3219 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT METAL 3338 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT BINDING 2547 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2577 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2578 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2595 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2596 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2622 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2623 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2638 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2710 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 100..101 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 114..115 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 205..206 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255" FT SITE 280..281 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 775..776 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1127..1128 FT /note="Cleavage; by host" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1345..1346 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1475..1476 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1932 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 1935 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 2093..2094 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2220..2221 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2243..2244 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2491..2492 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2505 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2508 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2509 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2511 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2516 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2520 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2552 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2637 FT /note="Essential for 2'-O-methyltransferase and N-7 FT methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2641 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2672 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2703 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2705 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2708 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT MOD_RES 2547 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P03314" FT CARBOHYD 183 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 347 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 433 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 905 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 982 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1134 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 2305 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2457 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 283..310 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 340..401 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 354..385 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 372..396 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 465..565 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 582..613 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 779..790 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 830..918 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 954..998 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1055..1104 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1066..1088 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1087..1091 FT /evidence="ECO:0000250|UniProtKB:P17763" FT STRAND 584..594 FT /evidence="ECO:0000244|PDB:2R29" FT STRAND 600..609 FT /evidence="ECO:0000244|PDB:2R29" FT STRAND 633..635 FT /evidence="ECO:0000244|PDB:2R29" FT STRAND 641..643 FT /evidence="ECO:0000244|PDB:2R29" FT STRAND 660..665 FT /evidence="ECO:0000244|PDB:2R29" FT HELIX 2500..2509 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2513..2521 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2525..2528 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2530..2537 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2549..2557 FT /evidence="ECO:0000244|PDB:3EVG" FT TURN 2558..2560 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2566..2571 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2577..2583 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2588..2594 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2612..2614 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2615..2618 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2623..2625 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2632..2636 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2645..2662 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2668..2674 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2679..2692 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2695..2697 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2709..2712 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2719..2732 FT /evidence="ECO:0000244|PDB:3EVG" FT HELIX 2733..2735 FT /evidence="ECO:0000244|PDB:3EVG" FT STRAND 2742..2745 FT /evidence="ECO:0000244|PDB:3EVG" SQ SEQUENCE 3391 AA; 379884 MW; 5EE11A74081C5177 CRC64; MNDQRKEAKN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLYMAL VAFLRFLTIP PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR SAGMIIMLIP TVMAFHLTTR NGEPHMIVSR QEKGKSLLFK TEVGVNMCTL MAMDLGELCE DTITYKCPLL RQNEPEDIDC WCNSTSTWVT YGTCTTMGEH RREKRSVALV PHVGMGLETR TETWMSSEGA WKHVQRIETW ILRHPGFTMM AAILAYTIGT THFQRALILI LLTAVTPSMT MRCIGMSNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFR CKKNMEGKVV QPENLEYTIV ITPHSGEEHA VGNDTGKHGK EIKITPQSSI TEAELTGYGT ITMECSPRTG LDFNEIVLLQ MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE PPFGDSYIII GVEPGQLKLN WFKKGSSIGQ MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVTLV LVGIVTLYLG VMVQADSGCV VSWKNKELKC GSGIFITDNV HTWTEQYKFQ PESPSKLASA IQKAHEEDIC GIRSVTRLEN LMWKQITPEL NHILSENEVK LTIMTGDIKG IMQAGKRSLR PQPTELKYSW KTWGKAKMLS TESHNQTFFI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLKEKQ DVFCDSKLMS AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKNCHW PKSHTLWSNG VLESEMIIPK NLAGPVSKHN YRPGYHTQIT GPWHLGKLEM DFDFCDGTTV VVTEDCGNRG PSLRTTTASG KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QVDNFSLGVL GMALFLEEML RTRVGTKHAI LLVAVSFVTL IIGNRSFRDL GRVMVMVGAT MTDDIGMGVT YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLSSQ STIPETILEL TDALALGMMV LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKTDWIP LALTIKGLNP TAIFLTTLSR TSKKRSWPLN EAIMAVGMVS ILASSLLKND IPMTGPLVAG GLLTVCYVLT GRSADLELER AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL TILIRRGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPMGK AELEDGAYRI KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL EGEWKEGEEV QVLALDPGKN PRAVQTKPGL FKTNAGTIGA VSLDFSPGTS GSPIIDKKGK VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF TMRLLSPVRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF PQSNAPIIDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KAGNDIAACL RKNGKKVIQL SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG PMPVTHSSAA QRRGRIGRNP KNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII PSMFEPEREK VDAIDGEYRL RGEARTTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD GVKNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRKSLTLNLI TEMGRLPTFM TQKARNALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL LTLLATVTGG IFLFLMSARG IGKMTLGMCC IITASILLWY AQIQPHWIAA SIILEFFLIV LLIPEPEKQR TPQDNQLTYV VIAILTVVAA TMANEMGFLE KTKKDLGLGS IATQQPESNI LDIDLRPASA WTLYAVATTF VTPMLRHSIE NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG CYSQVNPTTL TAALFLLVAH YAIIGPALQA KASREAQKRA AAGIMKNPTV DGITVIDLDP IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEALTLA TGPISTLSEG NPGRFWNTTI AVSMANIFRG SYLAGAGLLF SIMKNTTNTR RVTGNIGETL GEKWKSRLNA LGKSEFQIYK KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS AKLRWFVERN MVTPEGKVVD LGCGRGGWSY YCGGLKNVRE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFIPPEK CDTLLCDIGE SSPNPTVEAG RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP LSRNSTHEMY WVSNASGNIV SSVNMISRML INRFTMRYKK ATYEPDVDLG SGTRNIGIES EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY ETKQTGSASS MVNGVFRLLT KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV DTRTQEPKEG TKKLMKITAE WLWKELGKKK TPRMCTREEF TRKVRSNAAL GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET CVYNIMGKRE KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EEMVTNHMEG EHKKLAEAIF KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL NTFTNMEAQL IRQMEGEGVF KSIQHLTITE EIAVQNWLAR VGRERLSRMA ISGDDCVVKP LDDRLPSALT ALNDMGKIRK DIQQWEPSRG WNDWTQVPFC SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR ETACLGKSYA QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW AKNIQAAINQ VRSLIGNEEY TDYMPSMKRF RREEEEAGVL W //