ID   POLG_STEVM              Reviewed;        3412 AA.
AC   P09732; A3EZ58; Q88781; Q88782; Q88783; Q88784; Q88785; Q88786; Q88787;
AC   Q88788;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 2.
DT   02-SEP-2026, entry version 174.
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;
DE              EC=3.6.4.13;
DE     AltName: Full=Flavivirin protease NS3 catalytic subunit;
DE     AltName: Full=Non-structural protein 3;
DE   Contains:
DE     RecName: Full=Non-structural protein 4A;
DE              Short=NS4A;
DE   Contains:
DE     RecName: Full=Peptide 2k;
DE   Contains:
DE     RecName: Full=Non-structural protein 4B;
DE              Short=NS4B;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase/Methyltransferase NS5;
DE              EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE              EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE              EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE     AltName: Full=NS5;
DE   Flags: Fragment;
OS   St. louis encephalitis virus (strain MS1-7).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC   Amarillovirales; Flaviviridae; Orthoflavivirus; Orthoflavivirus louisense;
OC   St. Louis encephalitis virus.
OX   NCBI_TaxID=11081;
OH   NCBI_TaxID=9191; Agelaius tricolor (Tricolored blackbird).
OH   NCBI_TaxID=98964; Cardinalis cardinalis (Northern cardinal).
OH   NCBI_TaxID=8932; Columba livia (Rock dove).
OH   NCBI_TaxID=42429; Culex nigripalpus.
OH   NCBI_TaxID=7175; Culex pipiens (House mosquito).
OH   NCBI_TaxID=7176; Culex quinquefasciatus (Southern house mosquito) (Culex pungens).
OH   NCBI_TaxID=7177; Culex tarsalis (Encephalitis mosquito).
OH   NCBI_TaxID=28727; Cyanocitta cristata (Blue jay).
OH   NCBI_TaxID=84817; Euphagus cyanocephalus (Brewer's blackbird).
OH   NCBI_TaxID=30427; Haemorhous mexicanus (House finch) (Carpodacus mexicanus).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=60713; Mimus polyglottos (Northern mockingbird) (Turdus polyglottos).
OH   NCBI_TaxID=48849; Passer domesticus (House sparrow) (Fringilla domestica).
OH   NCBI_TaxID=9188; Turdus migratorius (American robin).
OH   NCBI_TaxID=47245; Zenaida macroura (Mourning dove) (Columba macroura).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=18374605; DOI=10.1016/j.ympev.2008.02.015;
RA   Baillie G.J., Kolokotronis S.O., Waltari E., Maffei J.G., Kramer L.D.,
RA   Perkins S.L.;
RT   "Phylogenetic and evolutionary analyses of St. Louis encephalitis virus
RT   genomes.";
RL   Mol. Phylogenet. Evol. 47:717-728(2008).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-1525.
RX   PubMed=3027980; DOI=10.1016/0042-6822(87)90409-0;
RA   Trent D.W., Kinney R.M., Johnson B.J.B., Vorndam A.V., Grant J.A.,
RA   Deubel V., Rice C.M., Hahn C.;
RT   "Partial nucleotide sequence of St. Louis encephalitis virus RNA:
RT   structural proteins, NS1, NS2A, and NS2B.";
RL   Virology 156:293-304(1987).
CC   -!- FUNCTION: [Capsid protein C]: Capsid protein C self-assembles to form
CC       an icosahedral capsid about 30 nm in diameter. The capsid encapsulates
CC       the genomic RNA (Probable). Plays a role in virus budding by binding to
CC       the cell membrane and gathering the viral RNA into a nucleocapsid that
CC       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, ECO:0000305}.
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 loop. prM is the only viral peptide matured
CC       by host furin in the trans-Golgi network probably to avoid catastrophic
CC       activation of the viral fusion activity in acidic Golgi compartment
CC       prior to virion release. prM-E cleavage is inefficient, and many
CC       virions are only partially matured. These uncleaved prM would play a
CC       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]: Type II fusion protein that binds to
CC       host cell surface receptor and mediates fusion between viral and
CC       cellular membranes (By similarity). The envelope protein E shifts from
CC       dimeric state to trimeric state to perform fusion with the host
CC       membrane (By similarity). The fusion loops of the three subunits come
CC       together to form a membrane-insertable tip containing aromatic residues
CC       (By similarity). Envelope protein is synthesized in the endoplasmic
CC       reticulum in the form of heterodimer with protein prM. They play a role
CC       in virion budding in the ER, and the newly formed immature particle is
CC       covered with 60 spikes composed of heterodimer between precursor prM
CC       and envelope protein E. The virion is transported to the Golgi
CC       apparatus where the low pH causes dissociation of PrM-E heterodimers
CC       and formation of E homodimers. prM-E cleavage is inefficient, and many
CC       virions are only partially matured. These uncleaved prM would play a
CC       role in immune evasion. {ECO:0000250|UniProtKB:P12823,
CC       ECO:0000250|UniProtKB:P14336, ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC       pathogenesis and viral replication. Once cleaved off the polyprotein,
CC       is targeted to three destinations: the viral replication cycle, the
CC       plasma membrane and the extracellular compartment. Essential for viral
CC       replication. Required for formation of the replication complex and
CC       recruitment of other non-structural proteins to the ER-derived membrane
CC       structures. Excreted as a hexameric lipoparticle that plays a role
CC       against host immune response. Antagonizing the complement function.
CC       Binds to the host macrophages and dendritic cells. Inhibits signal
CC       transduction originating from Toll-like receptor 3 (TLR3).
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC       replication complex that functions in virion assembly and antagonizes
CC       the host alpha/beta interferon antiviral response.
CC       {ECO:0000250|UniProtKB:P14335}.
CC   -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the
CC       serine protease function of NS3. May have membrane-destabilizing
CC       activity and form viroporins (By similarity).
CC       {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.
CC   -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities:
CC       serine protease, NTPase and RNA helicase. NS3 serine protease, in
CC       association with NS2B, performs its autocleavage and cleaves the
CC       polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-
CC       NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and
CC       unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE-
CC       ProRule:PRU00860}.
CC   -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC       the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC       during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC       required for the interferon antagonism activity of the latter.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-
CC       derived membrane vesicles where the viral replication takes place.
CC       Inhibits interferon (IFN)-induced host STAT1 phosphorylation and
CC       nuclear translocation, thereby preventing the establishment of cellular
CC       antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2
CC       translocation in the nucleus after IFN-alpha treatment.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase/Methyltransferase NS5]:
CC       Replicates the viral (+) and (-) RNA genome, and performs the capping
CC       of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-
CC       7 and ribose 2'-O positions. Besides its role in RNA genome
CC       replication, also prevents the establishment of cellular antiviral
CC       state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling
CC       pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby
CC       preventing activation of JAK-STAT signaling pathway.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
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=RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) +
CC         diphosphate; 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   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + phosphate + H(+); 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 + phosphate + H(+); Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000250|UniProtKB:Q9Q6P4};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-
CC         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};
CC   -!- CATALYTIC ACTIVITY:
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 + S-
CC         adenosyl-L-homocysteine + H(+); Xref=Rhea:RHEA:67020, Rhea:RHEA-
CC         COMP:17167, Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC         ChEBI:CHEBI:167609; EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00924};
CC   -!- SUBUNIT: [Capsid protein C]: Homodimer (By similarity). Interacts (via
CC       N-terminus) with host EXOC1 (via C-terminus); this interaction results
CC       in EXOC1 degradation through the proteasome degradation pathway (By
CC       similarity). Interacts (via the NLS) with host KPNA2/Importin alpha-1;
CC       this interaction allows the nuclear import of the capsid protein (By
CC       similarity). {ECO:0000250|UniProtKB:P17763,
CC       ECO:0000250|UniProtKB:Q01299}.
CC   -!- SUBUNIT: [Protein prM]: Heterodimer with envelope protein E; each spike
CC       of the immature virion in the ER/Golgi consists of three prM-E
CC       heterodimers. {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBUNIT: [Small envelope protein M]: Heterotetramer with envelope
CC       protein E, made up of two M-E dimers; in mature virion, prefusion
CC       state. {ECO:0000250|UniProtKB:Q01299}.
CC   -!- SUBUNIT: [Envelope protein E]: Homodimer; in mature virion, prefusion
CC       state (By similarity). Homotrimer; in mature virion, postfusion state
CC       (By similarity). Heterotetramer with the small membrane protein, made
CC       up of two M-E dimers; in mature virion, prefusion state (By
CC       similarity). Heterodimer with protein prM; each spike of the immature
CC       virion in the ER/Golgi consists of three prM-E heterodimers (By
CC       similarity). Interacts with the peptide pr; this interaction allows the
CC       stabilization of the E dimer at acidic pH (By similarity). Pr remains
CC       bound to the particle as long as the pH is acidic because of
CC       electrostatic complementarity, dissociation of pr occurs at neutral pH
CC       upon virus release from the infected cell (By similarity). Interacts
CC       with non-structural protein 1 (By similarity).
CC       {ECO:0000250|UniProtKB:P14336, ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC       secreted (By similarity). Interacts with envelope protein E (By
CC       similarity). NS1 interacts with NS4B (By similarity). Interacts with
CC       host complement protein CFH; this interaction leads to the degradation
CC       of C3 (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC       serine protease NS3. {ECO:0000250|UniProtKB:P03314}.
CC   -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC       serine protease NS3 (By similarity). May form homooligomers (By
CC       similarity). {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B (By
CC       similarity). Interacts with non-structural protein 2A (via N-terminus)
CC       (By similarity). Interacts with NS4B (By similarity). Interacts with
CC       unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC       stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC       (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC       NS3 (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBUNIT: [RNA-directed RNA polymerase/Methyltransferase NS5]: Homodimer
CC       (By similarity). Interacts with host STAT2; this interaction inhibits
CC       the phosphorylation of the latter, and, when all viral proteins are
CC       present (polyprotein), targets STAT2 for degradation (By similarity).
CC       Interacts with serine protease NS3 (By similarity). Interacts (via C-
CC       terminus) with host SCRIB (via PDZ3); this interaction targets NS5 to
CC       the cell membrane periphery and nucleus, thereby allowing efficient
CC       host nuclear STAT1 inhibition (By similarity). Interacts with host PAF1
CC       complex; the interaction may prevent the recruitment of the PAF1
CC       complex to interferon-responsive genes, and thus reduces the immune
CC       response (By similarity). {ECO:0000250|UniProtKB:P09866,
CC       ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:Q01299}.
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:P06935}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:P06935}. Host nucleus, host nucleolus
CC       {ECO:0000250|UniProtKB:Q01299}.
CC   -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC       {ECO:0000250|UniProtKB:P17763}. Note=Pr remains bound to the immature
CC       particle as long as the pH is acidic because of electrostatic
CC       complementarity, dissociation of pr occurs at neutral pH upon virus
CC       release from the infected cell. {ECO:0000250|UniProtKB:P14336}.
CC   -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC       {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=ER membrane retention is mediated by the
CC       transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC   -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC       {ECO:0000305}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=ER membrane retention is mediated by the
CC       transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC       {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane;
CC       Peripheral membrane protein; Lumenal side
CC       {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC       hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC       reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC       membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane
CC       protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side
CC       {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently
CC       associated to serine protease subunit NS2B. {ECO:0000255|PROSITE-
CC       ProRule:PRU00860}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC       reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated
CC       vesicles hosting the replication complex.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC       reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC       vesicles hosting the replication complex.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase/Methyltransferase
CC       NS5]: Host endoplasmic reticulum membrane; Peripheral membrane protein;
CC       Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P06935}.
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. {ECO:0000250|UniProtKB:P17763}.
CC   -!- DOMAIN: [Small envelope protein M]: The transmembrane domains contain
CC       an endoplasmic reticulum retention signal.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- DOMAIN: [Envelope protein E]: The transmembrane domains contain an
CC       endoplasmic reticulum retention signal. {ECO:0000250|UniProtKB:P17763}.
CC   -!- DOMAIN: [Protein prM]: The pr domain has a critical role in holding the
CC       spikes made of three prM-E heterodimers in a metastable conformation.
CC       {ECO:0000250|UniProtKB:P14336}.
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/Methyltransferase NS5]:
CC       Phosphorylated on serines residues. This phosphorylation may trigger
CC       NS5 nuclear localization. {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}.
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DR   EMBL; EF158050; ABN11812.1; -; Genomic_RNA.
DR   EMBL; M16614; AAA47786.1; -; Genomic_RNA.
DR   PDB; 4FG0; X-ray; 3.90 A; A=289-695.
DR   PDB; 7XT0; X-ray; 2.48 A; A=1676-2117.
DR   BMRB; P09732; -.
DR   SMR; P09732; -.
DR   MEROPS; S07.003; -.
DR   ABCD; P09732; 1 sequenced antibody.
DR   EvolutionaryTrace; P09732; -.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0030430; C:host cell cytoplasm; ISS:UniProtKB.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; ISS:UniProtKB.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR   GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004483; F:methyltransferase cap1 activity; IEA:UniProtKB-EC.
DR   GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-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 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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0039563; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039564; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:symbiont-mediated suppression 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; cd20761; capping_2-OMTase_Flaviviridae; 1.
DR   CDD; cd17931; DEXHc_viral_Ns3; 1.
DR   CDD; cd12149; Flavi_E_C; 1.
DR   CDD; cd17038; Flavi_M; 1.
DR   CDD; cd23204; Flavivirus_RdRp; 1.
DR   CDD; cd18806; SF2_C_viral; 1.
DR   FunFam; 1.20.1280.260:FF:000001; Envelope glycoprotein; 1.
DR   FunFam; 2.60.40.350:FF:000001; Envelope glycoprotein; 1.
DR   FunFam; 1.10.260.90:FF:000001; Genome polyprotein; 1.
DR   FunFam; 2.60.260.50:FF:000001; Genome polyprotein; 1.
DR   FunFam; 3.30.70.2840:FF:000001; Genome polyprotein; 1.
DR   FunFam; 3.30.70.2840:FF:000002; Genome polyprotein; 1.
DR   FunFam; 3.40.50.150:FF:000105; Genome polyprotein; 1.
DR   FunFam; 3.40.50.300:FF:000763; Genome polyprotein; 1.
DR   Gene3D; 1.10.10.930; -; 1.
DR   Gene3D; 1.10.260.90; -; 1.
DR   Gene3D; 1.20.1280.260; -; 1.
DR   Gene3D; 2.40.10.120; -; 2.
DR   Gene3D; 2.60.40.350; -; 1.
DR   Gene3D; 1.10.8.970; Flavivirus envelope glycoprotein M-like; 1.
DR   Gene3D; 2.60.260.50; Flavivirus polyprotein propeptide domain; 1.
DR   Gene3D; 3.30.70.2840; Flavivirus RNA-directed RNA polymerase, thumb domain; 3.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 2.60.98.10; Tick-borne Encephalitis virus Glycoprotein, domain 1; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   Gene3D; 3.30.67.10; Viral Envelope Glycoprotein, domain 2; 1.
DR   Gene3D; 3.30.387.10; Viral Envelope Glycoprotein, domain 3; 1.
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; IPR011492; Flavi_DEAD.
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; IPR011998; Flavi_Glycoprot_E_cen/dimer.
DR   InterPro; IPR001157; Flavi_NS1.
DR   InterPro; IPR000752; Flavi_NS2A.
DR   InterPro; IPR000487; Flavi_NS2B.
DR   InterPro; IPR001850; Flavi_NS3_S7.
DR   InterPro; IPR000404; Flavi_NS4A.
DR   InterPro; IPR001528; Flavi_NS4B.
DR   InterPro; IPR046811; Flavi_NS5_thumb.
DR   InterPro; IPR002535; Flavi_propep.
DR   InterPro; IPR038688; Flavi_propep_sf.
DR   InterPro; IPR047530; Flavi_RdRp.
DR   InterPro; IPR000208; Flavi_RdRp_fingers/palm.
DR   InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR   InterPro; IPR014412; Gen_Poly_FLV.
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-like.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR026490; mRNA_cap_0/1_MeTrfase.
DR   InterPro; IPR049486; NS3-hel_C_flaviviridae.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   NCBIfam; TIGR04240; flavi_E_stem; 1.
DR   Pfam; PF20907; Flav_NS3-hel_C; 1.
DR   Pfam; PF01003; Flavi_capsid; 1.
DR   Pfam; PF07652; Flavi_DEAD; 1.
DR   Pfam; PF21659; Flavi_E_stem; 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; PF20483; Flavi_NS5_thumb; 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; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF101257; Flavivirus capsid protein C; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   SUPFAM; SSF56983; Viral glycoprotein, central and dimerisation domains; 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; ATP-binding; Capsid protein;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein; Helicase;
KW   Host cytoplasm; Host endoplasmic reticulum; Host membrane; Host nucleus;
KW   Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host STAT1 by virus; Inhibition of host STAT2 by virus;
KW   Interferon antiviral system evasion; Membrane; Metal-binding;
KW   Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW   RNA-binding; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW   Secreted; Serine protease; Transcription; Transcription regulation;
KW   Transferase; Transmembrane; Transmembrane helix;
KW   Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW   Virus endocytosis by host; Virus entry into host cell; Zinc.
FT   CHAIN           1..>3412
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000405143"
FT   CHAIN           1..103
FT                   /note="Capsid protein C"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037735"
FT   PROPEP          104..121
FT                   /note="ER anchor for the capsid protein C, removed in
FT                   mature form by serine protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000405144"
FT   CHAIN           122..288
FT                   /note="Protein prM"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000405145"
FT   CHAIN           122..213
FT                   /note="Peptide pr"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037736"
FT   CHAIN           214..288
FT                   /note="Small envelope protein M"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037737"
FT   CHAIN           289..789
FT                   /note="Envelope protein E"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037738"
FT   CHAIN           790..1141
FT                   /note="Non-structural protein 1"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037739"
FT   CHAIN           1142..1368
FT                   /note="Non-structural protein 2A"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037740"
FT   CHAIN           1369..1499
FT                   /note="Serine protease subunit NS2B"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037741"
FT   CHAIN           1500..2117
FT                   /note="Serine protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000037742"
FT   CHAIN           2118..2243
FT                   /note="Non-structural protein 4A"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000405146"
FT   PEPTIDE         2244..2266
FT                   /note="Peptide 2k"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT                   /id="PRO_0000405147"
FT   CHAIN           2267..2524
FT                   /note="Non-structural protein 4B"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000405148"
FT   CHAIN           2525..>3412
FT                   /note="RNA-directed RNA polymerase/Methyltransferase NS5"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000405149"
FT   TOPO_DOM        2..108
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        109..129
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        130..247
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        248..268
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        269..273
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        274..288
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TOPO_DOM        289..741
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        742..762
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        763..768
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        769..789
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        790..1214
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1215..1235
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1236..1245
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1246..1266
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1267..1288
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1289..1303
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1304
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1305..1325
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1326..1339
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1340..1360
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1361..1369
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1370..1390
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1391..1393
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1394..1414
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1415..1471
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1472..1492
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1493..2167
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2168..2188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2189..2193
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        2194..2214
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2215
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2216..2236
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2237..2251
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2252..2266
FT                   /note="Helical; Note=Signal for NS4B"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2267..2308
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        2309..2329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2330..2376
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2377..2397
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2398..2440
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2441..2461
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2462..2466
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2467..2487
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2488..>3412
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1500..1677
FT                   /note="Peptidase S7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   DOMAIN          1680..1836
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          1847..2011
FT                   /note="Helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT   DOMAIN          2525..2790
FT                   /note="mRNA cap 0-1 NS5-type MT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   DOMAIN          3054..3206
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          2..15
FT                   /note="Interaction with host EXOC1"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   REGION          37..72
FT                   /note="Hydrophobic; homodimerization of capsid protein C"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   REGION          386..399
FT                   /note="Fusion peptide loop"
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   REGION          1422..1461
FT                   /note="Interacts with and activates NS3 protease"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT   REGION          1684..1687
FT                   /note="Important for RNA-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P14340"
FT   REGION          2162..2166
FT                   /note="Regulates the ATPase activity of NS3 helicase"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT   REGION          2742..2746
FT                   /note="Interaction with host SCRIB"
FT                   /evidence="ECO:0000250|UniProtKB:Q01299"
FT   REGION          2771..2791
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           83..105
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   MOTIF           1784..1787
FT                   /note="DEAH box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   COMPBIAS        2771..2780
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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        1574
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   ACT_SITE        1634
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   ACT_SITE        2585
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   ACT_SITE        2742
FT                   /note="For 2'-O-MTase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         1693..1700
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   BINDING         2580
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2610
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2611
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2628
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2629
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2655
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2656
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2671
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2744
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2964
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         2968
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         2973
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         2976
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         3241
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         3257
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   BINDING         3376
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   SITE            81
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            92
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            103..104
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            121..122
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            213..214
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            288..289
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            789..790
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            1141..1142
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            1368..1369
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            1499..1500
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            1956
FT                   /note="Involved in NS3 ATPase and RTPase activities"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   SITE            1959
FT                   /note="Involved in NS3 ATPase and RTPase activities"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   SITE            2117..2118
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            2243..2244
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            2266..2267
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            2524..2525
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   SITE            2537
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2540
FT                   /note="mRNA cap binding; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2541
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2543
FT                   /note="mRNA cap binding; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2548
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2552
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2585
FT                   /note="Essential for 2'-O-methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2670
FT                   /note="Essential for 2'-O-methyltransferase and N-7
FT                   methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2674
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   SITE            2737
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2739
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2742
FT                   /note="Essential for 2'-O-methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   MOD_RES         2580
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P03314"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   CARBOHYD        919
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT   CARBOHYD        964
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT   CARBOHYD        996
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT   DISULFID        155..190
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        166..202
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        174..188
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        291..318
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   DISULFID        348..409
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        362..393
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   DISULFID        380..404
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        478..576
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   DISULFID        593..624
FT                   /evidence="ECO:0000250|UniProtKB:P06935"
FT   DISULFID        793..804
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        844..932
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        968..1012
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1069..1118
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1080..1101
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1102..1105
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   VARIANT         47
FT                   /note="I -> M"
FT   VARIANT         164
FT                   /note="V -> I"
FT   VARIANT         168
FT                   /note="N -> D"
FT   VARIANT         249..250
FT                   /note="VL -> FC"
FT   VARIANT         346
FT                   /note="E -> K"
FT   VARIANT         444
FT                   /note="F -> S"
FT   VARIANT         604
FT                   /note="A -> T"
FT   VARIANT         796
FT                   /note="D -> S"
FT   VARIANT         843
FT                   /note="I -> Y"
FT   VARIANT         955
FT                   /note="R -> Q"
FT   NON_TER         3412
FT   HELIX           1680..1683
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1688..1691
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1697..1713
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1718..1724
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1725..1734
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   TURN            1735..1737
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1740..1742
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1757..1761
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1762..1770
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1779..1785
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1791..1805
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1810..1814
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1832..1836
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1849..1853
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1858..1861
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1865..1876
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   TURN            1877..1879
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1882..1885
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   TURN            1887..1889
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1890..1897
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1903..1907
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1909..1912
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1920..1924
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1927..1934
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1939..1947
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1950..1957
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          1969..1973
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           1985..1995
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2000..2002
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2009..2014
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   TURN            2019..2022
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2027..2037
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2043..2051
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2060..2063
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2064..2067
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2079..2081
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2083..2085
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2087..2089
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2093..2096
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2097..2099
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   STRAND          2100..2103
FT                   /evidence="ECO:0007829|PDB:7XT0"
FT   HELIX           2104..2113
FT                   /evidence="ECO:0007829|PDB:7XT0"
SQ   SEQUENCE   3412 AA;  378483 MW;  F89336D9D434A11F CRC64;
     MSKKPGKPGR NRVVNMLKRG VSRVNPLTGL KRILGSLLDG RGPVRFILAI LTFFRFTALQ
     PTEALKRRWR AVDKRTALKH LNGFKRDLGS MLDTINRRPS KKRGGTRSLL GLAALIGLAS
     SLQLSTYQGK VLMSINKTDA QSAINIPSAN GANTCIVRAL DVGVMCKNDI TYLCPVLSAG
     NDPEDIDCWC DVEEVWVHYG RCTRMGHSRR SRRSISVQHH GDSTLATKNT PWLDTVKTTK
     YLTKVENWVL RNPGYALVAL AIGWMLGSNN TQRVVFVIML MLIAPAYSFN CLGTSNRDFV
     EGASGATWID LVLEGGSCVT VMAPEKPTLD FKVMKMEATE LATVREYCYE ATLDTLSTVA
     RCPTTGEAHN TKRSDPTFVC KRDVVDRGWG NGCGLFGKGS IDTCAKFTCK NKATGKTILR
     ENIKYEVAIF VHGSTDSTSH GNYFEQIGKN QAARFTISPQ APSFTANMGE YGTVTIDCEA
     RSGINTEDYY VFTVKEKSWL VNRDWFHDLN LPWTSPATTD WRNRETLVEF EEPHATKQTV
     VALGSQEGAL HTALAGAIPA TVSSSTLTLQ SGHLKCRAKL DKVKIKGTTY GMCDSAFTFS
     KNPADTGHGT VIVELQYTGS NGPCRVPISV TANLMDLTPV GRLVTVNPFI STGGANNKVM
     IEVEPPFGDS YIVVGRGTTQ INYHWHKEGS SIGKALATTW KGAQRLAVLG DTAWDFGSIG
     GVFNSIGKAV HQVFGGAFRT LFGGMSWITQ GLLGALLLWM GLQARDRSIS LTLLAVGGIL
     IFLATSVQAD SGCAIDLQRR ELKCGGGIFV YNDVEKWKSD YKYFPLTPTG LAHVIQEAHA
     NGICGIRSTS RLEHLMWENI QRELNAIFED NEIDLSVVVQ EDPKYYKRAP RRLKKLEDEL
     DYGWKKWGKT LFVEPRLGNN TFVVDGPETK ECPTANRAWN SFKVEDFGFG MVFTRLWLTI
     REENTTECDS AIIGTAIKGD RAVHSDLSYW IESKKNETWQ LERAVMGEVK SCTWPETHTL
     WGDGVVESEM IIPVTLGGPK SHHNKRNGYH TQTKGPWSEG EITLDFDYCP GTTVTVTEHC
     GNRGASLRTT TASGKLVTDW CCRSCSLPPL RYTTKDGCWY GMEIRPVKEE EAKLVKSRVT
     AGVAGGMEPF QLGLLVAFIA TQEVLKRRWT GKLTLTSLAV CLALLIFGNL TYMDLVRYLV
     LVGTAFAEMN TGGDVIHLAL VAVFKVQPAF LAGLFLRMQW SNQENILMVI GAAFLQMAAN
     DLKLEVLPIL NAMSIAWMLI RAMKEGKVAM YALPILCALT PGMRMAGLDV IRCLLLIIGI
     VTLLNERRES VAKKKGGYLL AAALCQAGVC SPLIMMGGLI LAHPNGKRSW PASEVLTGVG
     LMCALAGGLL EFEETSMVVP FAIAGLMYIT YTVSGKAAEM WIEKAADITW EQNAEITGTS
     PRLDVDLDSH GNFKLLNDPG APVHLFALRF ILLGLSARFH WFIPFGVLGF WLLGKHSKRG
     GALWDVPSPK VYPKCETKPG IYRIMTRGIL GTFQAGVGVM HEGVFHTMWH ATEGAVLRNG
     EGRLDPYAGD VRNDLISYGG PWKLSATWDG TEEVQMIAVA PGKPAINVQT TPGVFKTPFG
     TIGAVTLDFP KGTSGSPIIN KKGEIIGLYG NGVLIGQGEY VSGIIQGERT EEPIPDAYNE
     EMLRKRKLTV LELHPGAGKT RKVLPQIIKD CIQKRLRTAV LAPTRVVACE IAEALKGLPI
     RYLTPAVRNE HQGNEIVDVM CHATLTQKLL TPTRVPNYQV YIMDEAHFID PASIAARGYI
     STKVELGEAA AIFMTATPPG TNDPFPDSNS PILDVEAQVP DKAWSTGYEW ITNFTGRTVW
     FVPSVKSGNE IAICLQKAGK RVIQLNRKSF DTEYPKTKNN EWDFVVTTDI SEMGANFGAH
     RVIDSRKCVK PVILEDDDRV ILNGPMAITS ASAAQRRGRI GRNPSQIGDE YHYGGATNED
     DHDLANWTEA KILLDNIYLP NGLVAQMYQP ERDKVFTMDG EFRLRGEERK NFVELMRNGD
     LPVWLAYKVA SNGHSYQDRS WCFTGQTNNT ILEDNNEVEV FTKTGDRKIL RPKWMDARVC
     CDYQALKSFK EFAAGKRSAL GMMEVMGRMP NHFWEKTVAA ADTLYLLGTS EANSRAHKEA
     LAELPDSLET LLLIGMLCVM SMGTFIFLMN RKGVGKMGLG AFVMTLATAL LWAAEVPGTQ
     IAGVLLIVFL LMIVLIPEPE KQRSQTDNQL AVFLICIMTL MGVVAANEMG LLEKTKSDIA
     KLFGSQPGSV GFATRTTPWD ISLDIKPATA WALYAAATMV MTPLIKHLIT TQYVNFSLTA
     IASQAGVLLG LTNGMPFTAM DLSVPLLVLG CWNQMTLPSL AVAVMLLAIH YAFMIPGWQA
     EAMRAAQRRT AAGIMKNAVV DGIVATDIPD LSPATPMTEK KMGQILLIAA AVLAVLVRPG
     ICSIKEFGVL GSAALVTLIE GTAGVVWNCT TAVGLCNLMR GGWLAGMSIT WTVYKNVDKP
     KGKRGGGKGA TLGEIWKSRL NQLTRAEFMA YRKDGIVEVD RAPARKARRE GRLTGGHPVS
     RGSAKLRWIT ERGFVKPMGK VVDLGCGRGG WSYYCATLKH VQEVKGFTKG GPGHEEPQLM
     QSYGWNLVHM KSGVDVFHKP AEPADTVLCD IGESNPSCEV EEARTARVLD MVEEWLKKGA
     TEFCIKVLCP YTPKIIEKLE KLQRKYGGGL VRVPLSRNST HEMYWVSGAA GNIIHAVSMT
     SQVLMGRMDK QNRSGPRYEE DVNLGSGTRS VGKLTEKPDL RKVGERIRRL REEYQQTWTY
     DHNNPYRTWN YHGSYEVKPT GSASSMVNGV VRLLSKPWDM ITNVTTMAMT DTTPFGQQRV
     FKEKVDTKAP EPPLGVAQIM DVTTDWLWDF VAREKKPRVC TPEEFKAKVN SHAALGAMFE
     EQNQWSSARE AVEDPKFWEM VDEEREAHLK GECHTCIYNM MGKREKKTGE FGKAKGSRAI
     WYMWLGARFL EFEALGFLNE DHWMSRENSY GGVEGKGLQK LGYILQEISQ IPGGKMYADD
     TAGWDTRITK EDLKNEAKIT KRMEERHRKL AEAIIDLTYR HKVVKVMRPG PDGKTYMDVI
     SREDQRGSGQ VVTYALNTFT NLAVQLIRCM EAEGVVDEDD ITRVRLGRLA KAVEWLRKNG
     PERLSRMAVS GDDCVVKPID DRFATALHFL NNMSKIRKDI QEWKPSTGWH NWQEVPFCSH
     HFNELMLKDG RTIVVPCRSQ DELIGRARIS PGAGWNVKET ACLSKSYAQM WLLMYFHRRD
     LRMMANAICS AVPVNWVPTG RTTWSIHGKG EWMTTEDMLS VWNRVWIEEN EYMKDKTPLA
     AWNDIPYLGK REDIWCGSLI GTRTRATWAE NIYAPIMQIR NLIGEEEYRD YM
//