ID   POLG_DEN3M              Reviewed;        3390 AA.
AC   Q6YMS3;
DT   12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   04-NOV-2026, entry version 150.
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/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=Non-structural protein 5;
GN   Name=pol;
OS   Dengue virus type 3 (strain Martinique/1243/1999) (DENV-3).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC   Amarillovirales; Flaviviridae; Orthoflavivirus; Euflavivirus;
OC   Orthoflavivirus denguei; Dengue virus.
OX   NCBI_TaxID=408691;
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].
RX   PubMed=14605161; DOI=10.1128/jcm.41.11.5195-5198.2003;
RA   Peyrefitte C.N., Couissinier-Paris P., Mercier-Perennec V., Bessaud M.,
RA   Martial J., Kenane N., Durand J.-P.A., Tolou H.J.;
RT   "Genetic characterization of newly reintroduced dengue virus type 3 in
RT   Martinique (French West Indies).";
RL   J. Clin. Microbiol. 41:5195-5198(2003).
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 heterodimers of precursor prM and
CC       envelope protein E (By similarity). Envelope protein exposes a
CC       positively-charged pr-binding pocket at the E dimer interface, inducing
CC       (prM/E)2 dimer formation to generate smooth particles in the Golgi (By
CC       similarity). The virion is transported to the Golgi apparatus where the
CC       low pH causes dissociation of PrM-E heterodimers and formation of E
CC       homodimers (By similarity). prM-E cleavage is inefficient, and many
CC       virions are only partially matured. These uncleaved prM would play a
CC       role in immune evasion (By similarity). Pr is shed from the particle
CC       upon subsequent secretion into the extracellular environment, leaving
CC       an activated particle, prone to mediate acidic pH-triggered membrane
CC       fusion upon entry into a target cell (By similarity).
CC       {ECO:0000250|UniProtKB:P12823, ECO:0000250|UniProtKB:P14336,
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 RIGI 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/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: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=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   -!- 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. Interacts (via N-terminus) with
CC       host EXOC1 (via C-terminus); this interaction results in EXOC1
CC       degradation through the proteasome degradation pathway. Interacts (via
CC       the NLS) with host KPNA2/Importin alpha-1; this interaction allows the
CC       nuclear import of the capsid protein (By similarity).
CC       {ECO:0000250|UniProtKB:P17763, 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. 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. {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       AUP1; the interaction occurs in the presence of Dengue virus NS4B and
CC       induces lipophagy which facilitates production of virus progeny
CC       particles (By similarity). {ECO:0000250|UniProtKB:P17763,
CC       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/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). Interacts with host KPNA2/importin-alpha;
CC       this interaction allows the nuclear localization of NS5 (By
CC       similarity). {ECO:0000250|UniProtKB:P09866,
CC       ECO:0000250|UniProtKB:P12823, ECO:0000250|UniProtKB:P17763,
CC       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:P17763}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:P17763}. 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: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/Methyltransferase
CC       NS5]: Host 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: [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   -!- DOMAIN: [RNA-directed RNA polymerase/Methyltransferase NS5]: The C-
CC       terminal 18 amino acids are important for the subcellular location of
CC       NS5. {ECO:0000250|UniProtKB:P12823}.
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: [Serine protease NS3]: Acetylated by host KAT5. Acetylation
CC       modulates NS3 RNA-binding and unwinding activities and plays an
CC       important positive role for viral replication.
CC       {ECO:0000250|UniProtKB:Q32ZE1}.
CC   -!- PTM: [RNA-directed RNA polymerase/Methyltransferase NS5]: Sumoylation
CC       of RNA-directed RNA polymerase NS5 increases NS5 protein stability
CC       allowing proper viral RNA replication. {ECO:0000250|UniProtKB:P29990}.
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; AY099337; AAM51538.1; -; Genomic_RNA.
DR   SMR; Q6YMS3; -.
DR   MEROPS; S07.001; -.
DR   GlyCosmos; Q6YMS3; 10 sites, No reported glycans.
DR   BRENDA; 3.4.21.91; 9648.
DR   PRO; PR:Q6YMS3; -.
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:0033650; C:host cell mitochondrion; 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; IEA:RHEA.
DR   GO; GO:0015267; F:channel activity; IEA:UniProtKB-KW.
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:0060090; F:molecular adaptor activity; IEA:UniProtKB-ARBA.
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:0034220; P:monoatomic ion transmembrane transport; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:symbiont-mediated activation of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0039545; P:symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR   GO; GO:0039574; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 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; 1.10.10.930: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; 2.40.10.10; Trypsin-like serine proteases; 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   3: Inferred from homology;
KW   Acetylation; Activation of host autophagy by virus; ATP-binding;
KW   Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein; Helicase;
KW   Host cytoplasm; Host endoplasmic reticulum; Host membrane;
KW   Host mitochondrion; Host nucleus; Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW   Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus;
KW   Interferon antiviral system evasion; Ion channel; Ion transport; Membrane;
KW   Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW   Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW   Phosphoprotein; Protease; RNA-binding; RNA-directed RNA polymerase;
KW   S-adenosyl-L-methionine; Secreted; Serine protease; 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_0000405224"
FT   CHAIN           1..100
FT                   /note="Capsid protein C"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268073"
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_0000268074"
FT   CHAIN           115..280
FT                   /note="Protein prM"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268075"
FT   CHAIN           115..205
FT                   /note="Peptide pr"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268076"
FT   CHAIN           206..280
FT                   /note="Small envelope protein M"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268077"
FT   CHAIN           281..773
FT                   /note="Envelope protein E"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268078"
FT   CHAIN           774..1125
FT                   /note="Non-structural protein 1"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268079"
FT   CHAIN           1126..1343
FT                   /note="Non-structural protein 2A"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268080"
FT   CHAIN           1344..1473
FT                   /note="Serine protease subunit NS2B"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268082"
FT   CHAIN           1474..2092
FT                   /note="Serine protease NS3"
FT                   /id="PRO_0000268083"
FT   CHAIN           2093..2219
FT                   /note="Non-structural protein 4A"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268084"
FT   PEPTIDE         2220..2242
FT                   /note="Peptide 2k"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268085"
FT   CHAIN           2243..2490
FT                   /note="Non-structural protein 4B"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268086"
FT   CHAIN           2491..3390
FT                   /note="RNA-directed RNA polymerase/Methyltransferase NS5"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268087"
FT   TOPO_DOM        1..100
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        101..120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        121..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"
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          1820..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 loop"
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   REGION          2706..2710
FT                   /note="Interaction with host SCRIB"
FT                   /evidence="ECO:0000250|UniProtKB:Q01299"
FT   REGION          3374..3376
FT                   /note="Interaction with host KPNA2"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   MOTIF           83..101
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
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   MOTIF           2810..2857
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   MOTIF           3374..3381
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
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:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2931
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2936
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2939
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         3202
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         3218
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
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            78
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            81
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            88
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            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   SITE            3374
FT                   /note="Important for NS5 nuclear subcellular location"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   MOD_RES         1862
FT                   /note="N6-acetyllysine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q32ZE1"
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|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        347
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        433
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        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        148..182
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        159..194
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        167..180
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
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..1085
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1086..1089
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
SQ   SEQUENCE   3390 AA;  377956 MW;  02948C3E4A4A4C39 CRC64;
     MNNQRKKTGK PSINMLKRVR NRVSTGSQLA KRFSKGLLNG QGPMKLVMAF IAFLRFLAIP
     PTAGVLARWG TFKKSGAIKV LKGFKKEISN MLSIINKRKK TSLCLMMIMP AALAFHLTSR
     DGEPRMIVGK NERGKSLLFK TASGINMCTL IAMDLGEMCD DTVTYKCPHI TEVEPEDIDC
     WCNLTSTWVT YGTCNQAGER RRDKRSVALA PHVGMGLDTR TQTWMSAEGA WRQVEKVETW
     ALRHPGFTIL ALFLAHYIGT SLTQKVVIFI LLMLVTPSMT MRCVGVGNRD FVEGLSGATW
     VDVVLEHGGC VTTMAKNKPT LDIELQKTEA TQLATLRKLC IEGKITNITT DSRCPTQGEA
     VLPEEQDQNY VCKHTYVDRG WGNGCGLFGK GSLVTCAKFQ CLEPIEGKVV QYENLKYTVI
     ITVHTGDQHQ VGNETQGVTA EITPQASTTE AILPEYGTLG LECSPRTGLD FNEMILLTMK
     NKAWMVHRQW FFDLPLPWTS GATTETPTWN RKELLVTFKN AHAKKQEVVV LGSQEGAMHT
     ALTGATEIQN SGGTSIFAGH LKCRLKMDKL ELKGMSYAMC TNTFVLKKEV SETQHGTILI
     KVEYKGEDAP CKIPFSTEDG QGKAHNGRLI TANPVVTKKE EPVNIEAEPP FGESNIVIGI
     GDNALKINWY KKGSSIGKMF EATARGARRM AILGDTAWDF GSVGGVLNSL GKMVHQIFGS
     AYTALFSGVS WVMKIGIGVL LTWIGLNSKN TSMSFSCIAI GIITLYLGAV VQADMGCVIN
     WKGKELKCGS GIFVTNEVHT WTEQYKFQAD SPKRLATAIA GAWENGVCGI RSTTRMENLL
     WKQIANELNY ILWENNIKLT VVVGDIIGVL EQGKRTLTPQ PMELKYSWKT WGKAKIVTAE
     TQNSSFIIDG PNTPECPSAS RAWNVWEVED YGFGVFTTNI WLKLREVYTQ LCDHRLMSAA
     VKDERAVHAD MGYWIESQKN GSWKLEKASL IEVKTCTWPK SHTLWSNGVL ESDMIIPKSL
     AGPISQHNHR PGYHTQTAGP WHLGKLELDF NYCEGTTVVI TENCGTRGPS LRTTTVSGKL
     IHEWCCRSCT LPPLRYMGED GCWYGMEIRP ISEKEENMVK SLVSAGSGKV DNFTMGVLCL
     AILFEEVMRG KFGKKHMIAG VFFTFVLLLS GQITWRDMAH TLIMIGSNAS DRMGMGVTYL
     ALIATFKIQP FLALGFFLRK LTSRENLLLG VGLAMATTLQ LPEDIEQMAN GIALGLMALK
     LITQFETYQL WTALISLTCS NTMFTLTVAW RTATLILAGV SLLPVCQSSS MRKTDWLPMA
     VAAMGVPPLP LFIFSLKDTL KRRSWPLNEG VMAVGLVSIL ASSLLRNDVP MAGPLVAGGL
     LIACYVITGT SADLTVEKAA DITWEEEAEQ TGVSHNLMIT VDDDGTMRIK DDETENILTV
     LLKTALLIVS GVFPYSIPAT LLVWHTWQKQ TQRSGVLWDV PSPPETQKAE LEEGVYRIKQ
     QGIFGKTQVG VGVQKEGVFH TMWHVTRGAV LTYNGKRLEP NWASVKKDLI SYGGGWRLSA
     QWQKGEEVQV IAVEPGKNPK NFQTMPGTFQ TTTGEIGAIA LDFKPGTSGS PIINREGKVV
     GLYGNGVVTK NGGYVSGIAQ TNAEPDGPTP ELEEEMFKKR NLTIMDLHPG SGKTRKYLPA
     IVREAIKRRL RTLILAPTRV VAAEMEEALK GLPIRYQTTA TKSEHTGREI VDLMCHATFT
     MRLLSPVRVP NYNLIIMDEA HFTDPASIAA RGYISTRVGM GEAAAIFMTA TPPGTADAFP
     QSNAPIQDEE RDIPERSWNS GNEWITDFAG KTVWFVPSIK AGNDIANCLR KNGKKVIQLS
     RKTFDTEYQK TKLNDWDFVV TTDISEMGAN FKADRVIDPR RCLKPVILTD GPERVILAGP
     MPVTAASAAQ RRGRVGRNPQ KENDQYIFTG QPLNNDEDHA HWTEAKMLLD NINTPEGIIP
     ALFEPEREKS AAIDGEYRLK GESRKTFVEL MRRGDLPVWL AHKVASEGIK YTDRKWCFDG
     QRNNQILEEN MDVEIWTKEG EKKKLRPRWL DARTYSDPLA LKEFKDFAAG RKSIALDLVT
     EIGRVPSHLA HRTRNALDNL VMLHTSEHGG RAYRHAVEEL PETMETLLLL GLMILLTGGA
     MLFLISGKGI GKTSIGLICV IASSGMLWMA EIPLQWIASA IVLEFFMMVL LIPEPEKQRT
     PQDNQLAYVV IGILTLAAII AANEMGLLET TKRDLGMSKE PGVVSPTSYL DVDLHPASAW
     TLYAVATTVI TPMLRHTIEN STANVSLAAI ANQAVVLMGL DKGWPISKMD LGVPLLALGC
     YSQVNPLTLT AAVLLLITHY AIIGPGLQAK ATREAQKRTA AGIMKNPTVD GIMTIDLDPV
     IYDSKFEKQL GQVMLLVLCA VQLLLMRTSW ALCEALTLAT GPITTLWEGS PGKFWNTTIA
     VSMANIFRGS YLAGAGLAFS IMKSVGTGKR GTGSQGETLG EKWKKKLNQL SRKEFDLYKK
     SGITEVDRTE AKEGLKRGEI THHAVSRGSA KLQWFVERNM VIPEGRVIDL GCGRGGWSYY
     CAGLKKVTEV RGYTKGGPGH EEPVPMSTYG WNIVKLMSGK DVFYLPPEKC DTLLCDIGES
     SPSPTVEESR TIRVLKMVEP WLKNNQFCIK VLNPYMPTVI EHLERLQRKH GGMLVRNPLS
     RNSTHEMYWI SNGTGNIVAS VNMVSRLLLN RFTMTHRRPT IEKDVDLGAG TRHVNAEPET
     PNMDVIGERI KRIKEEHNST WHYDDENPYK TWAYHGSYEV KATGSASSMI NGVVKLLTKP
     WDVVPMVTQM AMTDTTPFGQ QRVFKEKVDT RTPRSMPGTR RVMGITAEWL WRTLGRNKKP
     RLCTREEFTK KVRTNAAMGA VFTEENQWDS AKAAVEDEDF WKLVDREREL HKLGKCGSCV
     YNMMGKREKK LGEFGKAKGS RAIWYMWLGA RYLEFEALGF LNEDHWFSRE NSYSGVEGEG
     LHKLGYILRD ISKIPGGAMY ADDTAGWDTR ITEDDLHNEE KITQQMDPEH RQLANAIFKL
     TYQNKVVKVQ RPTPTGTVMD IISRKDQRGS GQVGTYGLNT FTNMEAQLIR QMEGEGVLSK
     ADLENPHLPE KKITQWLETK GVERLKRMAI SGDDCVVKPI DDRFANALLA LNDMGKVRKD
     IPQWQPSKGW HDWQQVPFCS HHFHELIMKD GRKLVVPCRP QDELIGRARI SQGAGWSLRE
     TACLGKAYAQ MWSLMYFHRR DLRLASNAIC SAVPVHWVPT SRTTWSIHAH HQWMTTEDML
     TVWNRVWIED NPWMEDKTPV TTWENVPYLG KREDQWCGSL IGLTSRATWA QNIPTAIQQV
     RSLIGNEEFL DYMPSMKRFR KEEESEGAIW
//