POLG_DEN3P
ID POLG_DEN3P Reviewed; 3390 AA.
AC P27915;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 182.
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, ECO:0000269|PubMed:21147775};
DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924, ECO:0000269|PubMed:21147775};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539, ECO:0000269|PubMed:26895240};
DE AltName: Full=Non-structural protein 5;
OS Dengue virus type 3 (strain Philippines/H87/1956) (DENV-3).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=408870;
OH NCBI_TaxID=53540; Aedimorphus.
OH NCBI_TaxID=53539; Diceromyia.
OH NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=53541; Stegomyia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2345967; DOI=10.1016/0042-6822(90)90037-r;
RA Osatomi K., Sumiyoshi H.;
RT "Complete nucleotide sequence of dengue type 3 virus genome RNA.";
RL Virology 176:643-647(1990).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 281-672.
RX PubMed=15613349; DOI=10.1128/jvi.79.2.1223-1231.2005;
RA Modis Y., Ogata S., Clements D., Harrison S.C.;
RT "Variable surface epitopes in the crystal structure of dengue virus type 3
RT envelope glycoprotein.";
RL J. Virol. 79:1223-1231(2005).
RN [3] {ECO:0007744|PDB:3P8Z, ECO:0007744|PDB:3P97}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2491-2752 IN COMPLEX WITH
RP IRON-SULFUR (4FE-4S-S-ADOMET), CATALYTIC ACTIVITY (RNA-DIRECTED RNA
RP POLYMERASE NS5), AND MUTAGENESIS OF PHE-2623; GLY-2638; ARG-2650; ARG-2653
RP AND LEU-2672.
RX PubMed=21147775; DOI=10.1074/jbc.m110.179184;
RA Lim S.P., Sonntag L.S., Noble C., Nilar S.H., Ng R.H., Zou G., Monaghan P.,
RA Chung K.Y., Dong H., Liu B., Bodenreider C., Lee G., Ding M., Chan W.L.,
RA Wang G., Jian Y.L., Chao A.T., Lescar J., Yin Z., Vedananda T.R.,
RA Keller T.H., Shi P.Y.;
RT "Small molecule inhibitors that selectively block dengue virus
RT methyltransferase.";
RL J. Biol. Chem. 286:6233-6240(2011).
RN [4] {ECO:0007744|PDB:5CCV}
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF 2491-3390, SUBUNIT (RNA-DIRECTED
RP RNA POLYMERASE NS5), AND CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE
RP NS5).
RX PubMed=26895240; DOI=10.1371/journal.ppat.1005451;
RA Klema V.J., Ye M., Hindupur A., Teramoto T., Gottipati K., Padmanabhan R.,
RA Choi K.H.;
RT "Dengue virus nonstructural protein 5 (NS5) assembles into a dimer with a
RT unique methyltransferase and polymerase interface.";
RL PLoS Pathog. 12:E1005451-E1005451(2016).
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. Interacts with host AUP1 which mediates induction of
CC lipophagy in host cells and facilitates production of virus progeny
CC particles (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29991, 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. {ECO:0000250|UniProtKB:P17763}.
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:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:26895240};
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: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924, ECO:0000269|PubMed:21147775};
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924,
CC ECO:0000269|PubMed:21147775};
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. Interacts with host AUP1; the interaction occurs in the presence
CC of Dengue virus NS4B and induces lipophagy which facilitates production
CC of virus progeny particles (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:P29991}.
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.
CC {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: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";
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DR EMBL; M93130; AAA99437.1; -; Genomic_RNA.
DR PIR; A34774; GNWVD3.
DR PDB; 1UZG; X-ray; 3.60 A; A/B=281-672.
DR PDB; 2J7U; X-ray; 1.85 A; A=2762-3390.
DR PDB; 2J7W; X-ray; 2.60 A; A=2762-3390.
DR PDB; 3P8Z; X-ray; 1.70 A; A/C=2491-2752.
DR PDB; 3P97; X-ray; 1.70 A; A/C=2491-2752.
DR PDB; 3UZE; X-ray; 2.04 A; C/D=573-673.
DR PDB; 3VTT; X-ray; 1.70 A; A/B=574-678.
DR PDB; 5CCV; X-ray; 3.60 A; A/B/C/D/E/F/G/H=2491-3390.
DR PDB; 5E9Q; X-ray; 1.79 A; A/C=2497-2752.
DR PDB; 5EC8; X-ray; 1.71 A; A/C=2491-2766.
DR PDB; 5EHG; X-ray; 2.02 A; A/C=2491-2766.
DR PDB; 5EHI; X-ray; 1.30 A; A/C=2491-2746.
DR PDB; 5EIF; X-ray; 1.50 A; A/C=2491-2766.
DR PDB; 5EIW; X-ray; 1.61 A; A/C=2491-2766.
DR PDB; 5EKX; X-ray; 1.76 A; A/B=2491-2766.
DR PDB; 7A3S; X-ray; 2.80 A; A/B/C=281-673.
DR PDBsum; 1UZG; -.
DR PDBsum; 2J7U; -.
DR PDBsum; 2J7W; -.
DR PDBsum; 3P8Z; -.
DR PDBsum; 3P97; -.
DR PDBsum; 3UZE; -.
DR PDBsum; 3VTT; -.
DR PDBsum; 5CCV; -.
DR PDBsum; 5E9Q; -.
DR PDBsum; 5EC8; -.
DR PDBsum; 5EHG; -.
DR PDBsum; 5EHI; -.
DR PDBsum; 5EIF; -.
DR PDBsum; 5EIW; -.
DR PDBsum; 5EKX; -.
DR PDBsum; 7A3S; -.
DR SMR; P27915; -.
DR DrugBank; DB04473; alpha-L-fucose.
DR MEROPS; S07.001; -.
DR iPTMnet; P27915; -.
DR ABCD; P27915; 3 sequenced antibodies.
DR EvolutionaryTrace; P27915; -.
DR PRO; PR:P27915; -.
DR Proteomes; UP000007200; 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:0016887; F:ATP hydrolysis activity; IEA:RHEA.
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; ISS:UniProtKB.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 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:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; 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; cd20761; capping_2-OMTase_Flaviviridae; 1.
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 Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
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; Direct protein sequencing;
KW Disulfide bond; 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..3390
FT /note="Genome polyprotein"
FT /id="PRO_0000405221"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037989"
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_0000037990"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308293"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308294"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037991"
FT CHAIN 281..773
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037992"
FT CHAIN 774..1125
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037993"
FT CHAIN 1126..1343
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037994"
FT CHAIN 1344..1473
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037995"
FT CHAIN 1474..2092
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037996"
FT CHAIN 2093..2219
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037997"
FT PEPTIDE 2220..2242
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308296"
FT CHAIN 2243..2490
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037998"
FT CHAIN 2491..3390
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037999"
FT TOPO_DOM 1..100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..243
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..723
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 724..744
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 745..750
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..1193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1194..1218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1219..1224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1225..1243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1244..1267
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1268..1288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1289
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1290..1308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1309..1315
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1316..1336
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1337..1344
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1345..1365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1366..1368
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1369..1389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1390..1443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1444..1464
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1465..2146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2147..2167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2168..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..2227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2228..2248
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT TOPO_DOM 2249..2273
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2274..2294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2295..2305
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2306..2326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2327..2346
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2347..2367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2368..2412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2413..2433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2434..2458
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2459..2479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2480..3390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1474..1651
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 1821..1986
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2492..2753
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3018..3168
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
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 1396..1435
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 2567..2570
FT /note="SUMO-interacting motif"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT ACT_SITE 1524
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1548
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1608
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2551
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2636
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2670
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2706
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1667..1674
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2546
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2576
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2577
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2594
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2595
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2621
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2622
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2637
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2708
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2927
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 2931
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 2936
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 2939
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 3202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 3218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26895240"
FT BINDING 3337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
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 773..774
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1125..1126
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1343..1344
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1473..1474
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 2490..2491
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2504
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 2508
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2510
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2515
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2519
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2551
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2636
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2640
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2670
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2701
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2703
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2706
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:15613349"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:15613349"
FT CARBOHYD 903
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 980
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1132
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1188
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2300
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2304
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2456
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 463..563
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 580..611
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 777..788
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 828..916
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 952..996
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1053..1102
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1064..1086
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1085..1089
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT MUTAGEN 2623
FT /note="F->A: No effect on N7 methylase activity; 35% loss
FT of 2'-O methylase activity."
FT /evidence="ECO:0000269|PubMed:21147775"
FT MUTAGEN 2638
FT /note="G->A: 70% loss of N7 methylase activity; 60% loss of
FT 2'-O methylase activity."
FT /evidence="ECO:0000269|PubMed:21147775"
FT MUTAGEN 2650
FT /note="R->A: 40% loss of N7 methylase activity; No effect
FT on loss of 2'-O methylase activity."
FT /evidence="ECO:0000269|PubMed:21147775"
FT MUTAGEN 2653
FT /note="R->A: 40% loss of N7 methylase activity; No effect
FT on loss of 2'-O methylase activity."
FT /evidence="ECO:0000269|PubMed:21147775"
FT MUTAGEN 2672
FT /note="L->A: No effect on N7 methylase activity; 80% loss
FT of 2'-O methylase activity."
FT /evidence="ECO:0000269|PubMed:21147775"
FT TURN 282..285
FT /evidence="ECO:0007829|PDB:1UZG"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 321..330
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 334..352
FT /evidence="ECO:0007829|PDB:7A3S"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 370..380
FT /evidence="ECO:0007829|PDB:7A3S"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 389..409
FT /evidence="ECO:0007829|PDB:7A3S"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:1UZG"
FT STRAND 438..446
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 448..453
FT /evidence="ECO:0007829|PDB:7A3S"
FT TURN 454..456
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 457..464
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 471..479
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 482..487
FT /evidence="ECO:0007829|PDB:7A3S"
FT HELIX 488..492
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 498..502
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:1UZG"
FT HELIX 512..514
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 516..519
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 527..530
FT /evidence="ECO:0007829|PDB:7A3S"
FT HELIX 535..541
FT /evidence="ECO:0007829|PDB:7A3S"
FT TURN 542..544
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 545..549
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 560..566
FT /evidence="ECO:0007829|PDB:7A3S"
FT TURN 573..576
FT /evidence="ECO:0007829|PDB:7A3S"
FT STRAND 577..579
FT /evidence="ECO:0007829|PDB:1UZG"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 594..596
FT /evidence="ECO:0007829|PDB:1UZG"
FT STRAND 598..604
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 615..618
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 628..631
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 635..637
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 643..648
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 651..661
FT /evidence="ECO:0007829|PDB:3VTT"
FT STRAND 665..671
FT /evidence="ECO:0007829|PDB:3VTT"
FT HELIX 2499..2509
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2512..2518
FT /evidence="ECO:0007829|PDB:5EHI"
FT TURN 2519..2522
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2524..2527
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2529..2536
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2548..2557
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2565..2570
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2576..2581
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2587..2593
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2611..2613
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2614..2617
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2622..2624
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2631..2635
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2644..2658
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2659..2661
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2666..2672
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2677..2690
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2693..2695
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2707..2712
FT /evidence="ECO:0007829|PDB:5EHI"
FT HELIX 2717..2730
FT /evidence="ECO:0007829|PDB:5EHI"
FT TURN 2731..2733
FT /evidence="ECO:0007829|PDB:5EHI"
FT STRAND 2740..2743
FT /evidence="ECO:0007829|PDB:5EHI"
SQ SEQUENCE 3390 AA; 378063 MW; 666E8F70F1E1756E CRC64;
MNNQRKKTGK PSINMLKRVR NRVSTGSQLA KRFSRGLLNG QGPMKLVMAF IAFLRFLAIP
PTAGVLARWG TFKKSGAIKV LKGFKKEISN MLSIINKRKK TSLCLMMMLP ATLAFHLTSR
DGEPRMIVGK NERGKSLLFK TASGINMCTL IAMDLGEMCD DTVTYKCPHI TEVEPEDIDC
WCNLTSTWVT YGTCNQAGEH RRDKRSVALA PHVGMGLDTR TQTWMSAEGA WRQVEKVETW
ALRHPGFTIL ALFLAHYIGT SLTQKVVIFI LLMLVTPSMT MRCVGVGNRD FVEGLSGATW
VDVVLEHGGC VTTMAKNKPT LDIELQKTEA TQLATLRKLC IEGKITNITT DSRCPTQGEA
ILPEEQDQNY VCKHTYVDRG WGNGCGLFGK GSLVTCAKFQ CLESIEGKVV QHENLKYTVI
ITVHTGDQHQ VGNETQGVTA EITSQASTAE AILPEYGTLG LECSPRTGLD FNEMILLTMK
NKAWMVHRQW FFDLPLPWTS GATTKTPTWN RKELLVTFKN AHAKKQEVVV LGSQEGAMHT
ALTGATEIQT SGGTSIFAGH LKCRLKMDKL KLKGMSYAMC LNTFVLKKEV SETQHGTILI
KVEYKGEDAP CKIPFSTEDG QGKAHNGRLI TANPVVTKKE EPVNIEAEPP FGESNIVIGI
GDKALKINWY RKGSSIGKMF EATARGARRM AILGDTAWDF GSVGGVLNSL GKMVHQIFGS
AYTALFSGVS WIMKIGIGVL LTWIGLNSKN TSMSFSCIAI GIITLYLGVV VQADMGCVIN
WKGKELKCGS GIFVTNEVHT WTEQYKFQAD SPKRVATAIA GAWENGVCGI RSTTRMENLL
WKQIANELNY ILWENDIKLT VVVGDITGVL EQGKRTLTPQ PMELKYSWKT WGLAKIVTAE
TQNSSFIIDG PSTPECPSAS RAWNVWEVED YGFGVFTTNI WLKLREVYTQ LCDHRLMSAA
VKDERAVHAD MGYWIESQKN GSWKLEKASL IEVKTCTWPK SHTLWSNGVL ESDMIIPKSL
AGPISQHNHR PGYHTQTAGP WHLGKLELDF NYCEGTTVVI SENCGTRGPS LRTTTVSGKL
IHEWCCRSCT LPPLRYMGED GCWYGMEIRP INEKEENMVK SLASAGSGKV DNFTMGVLCL
AILFEEVMRG KFGKKHMIAG VLFTFVLLLS GQITWRGMAH TLIMIGSNAS DRMGMGVTYL
ALIATFKIQP FLALGFFLRK LTSRENLLLG VGLAMAATLR LPEDIEQMAN GIALGLMALK
LITQFETYQL WTALVSLTCS NTIFTLTVAW RTATLILAGI SLLPVCQSSS MRKTDWLPMT
VAAMGVPPLP LFIFSLKDTL KRRSWPLNEG VMAVGLVSIL ASSLLRNDVP MAGPLVAGGL
LIACYVITGT SADLTVEKAA DVTWEEEAEQ TGVSHNLMIT VDDDGTMRIK DDETENILTV
LLKTALLIVS GIFPYSIPAT MLVWHTWQKQ TQRSGVLWDV PSPPETQKAE LEEGVYRIKQ
QGIFGKTQVG VGVQKEGVFH TMWHVTRGAV LTHNGKRLEP NWASVKKDLI SYGGGWRLSA
QWQKGEEVQV IAVEPGKNPK NFQTMPGIFQ TTTGEIGAIA LDFKPGTSGS PIINREGKVV
GLYGNGVVTK NGGYVSGIAQ TNAEPDGPTP ELEEEMFKKR NLTIMDLHPG SGKTRKYLPA
IVREAIKRRL RTLILAPTRV VAAEMEEAMK GLPIRYQTTA TKSEHTGREI VDLMCHATFT
MRLLSPVRVP NYNLIIMDEA HFTDPASIAA RGYISTRVGM GEAAAIFMTA TPPGTADAFP
QSNAPIQDEE RDIPERSWNS GNEWITDFVG KTVWFVPSIK AGNVIANCLR KNGKKVIQLS
RKTFDTEYQK TKLNDWDFVV TTDISEMGAN FIADRVIDPR RCLKPVILTD GPERVILAGP
MPVTVASAAQ RRGRVGRNPQ KENDQYIFMG QPLNKDEDHA HWTEAKMLLD NINTPEGIIP
ALFEPEREKS AAIDGEYRLK GESRKTFVEL MRRGDLPVWL AHKVASEGIK YTDRKWCFDG
ERNNQILEEN MDVEIWTKEG EKKKLRPRWL DARTYSDPLA LKEFKDFAAG RKSIALDLVT
EIGRVPSHLA HRTRNALDNL VMLHTSEHGG RAYRHAVEEL PETMETLLLL GLMILLTGGA
MLFLISGKGI GKTSIGLICV IASSGMLWMA DVPLQWIASA IVLEFFMMVL LIPEPEKQRT
PQDNQLAYVV IGILTLAAIV AANEMGLLET TKRDLGMSKE PGVVSPTSYL DVDLHPASAW
TLYAVATTVI TPMLRHTIEN STANVSLAAI ANQAVVLMGL DKGWPISKMD LGVPLLALGC
YSQVNPLTLI AAVLLLVTHY AIIGPGLQAK ATREAQKRTA AGIMKNPTVD GIMTIDLDPV
IYDSKFEKQL GQVMLLVLCA VQLLLMRTSW ALCEVLTLAT GPITTLWEGS PGKFWNTTIA
VSMANIFRGS YLAGAGLALS IMKSVGTGKR GTGSQGETLG EKWKKKLNQL SRKEFDLYKK
SGITEVDRTE AKEGLKRGEI THHAVSRGSA KLQWFVERNM VIPEGRVIDL GCGRGGWSYY
CAGLKKVTEV RGYTKGGPGH EEPVPMSTYG WNIVKLMSGK DVFYLPPEKC DTLLCDIGES
SPSPTVEESR TIRVLKMVEP WLKNNQFCIK VLNPYMPTVI EHLERLQRKH GGMLVRNPLS
RNSTHEMYWI SNGTGNIVSS VNMVSRLLLN RFTMTHRRPT IEKDVDLGAG TRHVNAEPET
PNMDVIGERI KRIKEEHSST WHYDDENPYK TWAYHGSYEV KATGSASSMI NGVVKLLTKP
WDVVPMVTQM AMTDTTPFGQ QRVFKEKVDT RTPRPMPGTR KVMEITAEWL WRTLGRNKRP
RLCTREEFTK KVRTNAAMGA VFTEENQWDS ARAAVEDEEF WKLVDREREL HKLGKCGSCV
YNMMGKREKK LGEFGKAKGS RAIWYMWLGA RYLEFEALGF LNEDHWFSRE NSYSGVEGEG
LHKLGYILRD ISKIPGGAMY ADDTAGWDTR ITEDDLHNEE KITQQMDPEH RQLANAIFKL
TYQNKVVKVQ RPTPKGTVMD IISRKDQRGS GQVGTYGLNT FTNMEAQLIR QMEGEGVLSK
ADLENPHPLE KKITQWLETK GVERLKRMAI SGDDCVVKPI DDRFANALLA LNDMGKVRKD
IPQWQPSKGW HDWQQVPFCS HHFHELIMKD GRKLVVPCRP QDELIGRARI SQGAGWSLRE
TACLGKAYAQ MWTLMYFHRR DLRLASNAIC SAVPVHWVPT SRTTWSIHAH HQWMTTEDML
TVWNRVWIED NPWMEDKTPV TTWEDVPYLG KREDQWCGSL IGLTSRATWA QNILTAIQQV
RSLIGNEEFL DYMPSMKRFR KEEESEGAIW
