ID   POLG_DEN4P              Reviewed;        3387 AA.
AC   Q58HT7;
DT   12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   02-SEP-2026, entry version 148.
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;
OS   Dengue virus type 4 (strain Philippines/H241/1956) (DENV-4).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC   Amarillovirales; Flaviviridae; Orthoflavivirus; Orthoflavivirus denguei;
OC   Dengue virus.
OX   NCBI_TaxID=408686;
OH   NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH   NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH   NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Yip A., Schreiber M., Liu W., Khoo C.A., Wong C., Hibberd M., Vasudevan S.;
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC       May reduce immune responses by preventing the recruitment of the host
CC       PAF1 complex to interferon-responsive genes (By similarity).
CC       {ECO:0000250|UniProtKB:P09866, 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:P09866,
CC       ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles
CC       hosting the replication complex. NS5 protein is mainly localized in the
CC       nucleus rather than in ER vesicles, especially in the DENV 2, 3, 4
CC       serotypes. {ECO:0000250|UniProtKB:P17763}.
CC   -!- DOMAIN: [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; AY947539; AAX48017.1; -; Genomic_RNA.
DR   PDB; 4AM0; X-ray; 3.02 A; Q/R/S/T=574-674.
DR   PDB; 7VMV; X-ray; 3.35 A; A/C/E/G=1392-1439.
DR   PDB; 8WBB; EM; 2.90 A; A/a=775-1126.
DR   PDB; 8WBC; EM; 3.03 A; A/B/a/b=775-1126.
DR   PDB; 8WBD; EM; 2.90 A; A/B/C/a/b/c=775-1126.
DR   PDB; 8WBE; EM; 3.00 A; A/B/C/a/b/c=775-1126.
DR   BMRB; Q58HT7; -.
DR   EMDB; EMD-37419; -.
DR   EMDB; EMD-37420; -.
DR   EMDB; EMD-37421; -.
DR   EMDB; EMD-37422; -.
DR   SMR; Q58HT7; -.
DR   BindingDB; Q58HT7; -.
DR   MEROPS; S07.001; -.
DR   ABCD; Q58HT7; 4 sequenced antibodies.
DR   EvolutionaryTrace; Q58HT7; -.
DR   PRO; PR:Q58HT7; -.
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:0008289; F:lipid binding; IEA:UniProtKB-ARBA.
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; 1.10.260.90:FF:000001; Genome polyprotein; 1.
DR   FunFam; 1.10.8.970:FF:000002; Genome polyprotein; 1.
DR   FunFam; 2.40.10.120:FF:000008; 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; 3.30.70.2840:FF:000004; 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.
DR   PDBsum; 4AM0; -.
DR   PDBsum; 7VMV; -.
DR   PDBsum; 8WBB; -.
DR   PDBsum; 8WBC; -.
DR   PDBsum; 8WBD; -.
DR   PDBsum; 8WBE; -.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activation of host autophagy by virus;
KW   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;
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..3387
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000405227"
FT   CHAIN           1..99
FT                   /note="Capsid protein C"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268103"
FT   PROPEP          100..113
FT                   /note="ER anchor for the capsid protein C, removed in
FT                   mature form by serine protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268104"
FT   CHAIN           114..279
FT                   /note="Protein prM"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268105"
FT   CHAIN           114..204
FT                   /note="Peptide pr"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268106"
FT   CHAIN           205..279
FT                   /note="Small envelope protein M"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268107"
FT   CHAIN           280..774
FT                   /note="Envelope protein E"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268108"
FT   CHAIN           775..1126
FT                   /note="Non-structural protein 1"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268109"
FT   CHAIN           1127..1344
FT                   /note="Non-structural protein 2A"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268110"
FT   CHAIN           1345..1474
FT                   /note="Serine protease subunit NS2B"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268111"
FT   CHAIN           1475..2092
FT                   /note="Serine protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268112"
FT   CHAIN           2093..2219
FT                   /note="Non-structural protein 4A"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268113"
FT   PEPTIDE         2220..2242
FT                   /note="Peptide 2k"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268114"
FT   CHAIN           2243..2487
FT                   /note="Non-structural protein 4B"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268115"
FT   CHAIN           2488..3387
FT                   /note="RNA-directed RNA polymerase/Methyltransferase NS5"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT                   /id="PRO_0000268116"
FT   TOPO_DOM        1..100
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        101..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..237
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        238..258
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        259..265
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        266..279
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        280..723
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        724..746
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        747..750
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        751..771
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        772..1194
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1195..1218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1219..1224
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1225..1243
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1244..1267
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1268..1288
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1289
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1290..1308
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1309..1316
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1317..1337
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1338..1345
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1346..1366
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1367..1369
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1370..1390
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1391..1437
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1438..1458
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1459..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..2225
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2226..2246
FT                   /note="Helical; Note=Signal for NS4B"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2247..2270
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        2271..2291
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2292..2301
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        2302..2322
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2323..2343
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2344..2364
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2365..2409
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2410..2430
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2431..2455
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2456..2476
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2477..3387
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1475..1652
FT                   /note="Peptidase S7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   DOMAIN          1654..1810
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          1820..1987
FT                   /note="Helicase C-terminal"
FT   DOMAIN          2489..2751
FT                   /note="mRNA cap 0-1 NS5-type MT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   DOMAIN          3016..3166
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          36..71
FT                   /note="Hydrophobic; homodimerization of capsid protein C"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   REGION          377..390
FT                   /note="Fusion peptide loop"
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   REGION          1397..1436
FT                   /note="Interacts with and activates NS3 protease"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT   REGION          1658..1661
FT                   /note="Important for RNA-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P14340"
FT   REGION          2704..2708
FT                   /note="Interaction with host SCRIB"
FT                   /evidence="ECO:0000250|UniProtKB:Q01299"
FT   REGION          3372..3374
FT                   /note="Interaction with host KPNA2"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   MOTIF           82..100
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           2564..2567
FT                   /note="SUMO-interacting motif"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   MOTIF           2808..2855
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   MOTIF           3372..3379
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   ACT_SITE        1525
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   ACT_SITE        1549
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   ACT_SITE        1609
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT   ACT_SITE        2548
FT                   /note="For 2'-O-MTase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   ACT_SITE        2633
FT                   /note="For 2'-O-MTase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   ACT_SITE        2668
FT                   /note="For 2'-O-MTase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   ACT_SITE        2704
FT                   /note="For 2'-O-MTase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         1667..1674
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   BINDING         2543
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2573
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2574
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2591
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2592
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2618
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2619
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2634
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2706
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   BINDING         2925
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2929
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2934
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         2937
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         3200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         3216
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   BINDING         3335
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT   SITE            77
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            80
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            87
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            91
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            94
FT                   /note="Homodimerization of capsid protein"
FT                   /evidence="ECO:0000250|UniProtKB:P12823"
FT   SITE            99..100
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            113..114
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            204..205
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT   SITE            279..280
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            774..775
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            1126..1127
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            1344..1345
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            1474..1475
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            1931
FT                   /note="Involved in NS3 ATPase and RTPase activities"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   SITE            1934
FT                   /note="Involved in NS3 ATPase and RTPase activities"
FT                   /evidence="ECO:0000250|UniProtKB:P14335"
FT   SITE            2092..2093
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            2219..2220
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            2242..2243
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            2487..2488
FT                   /note="Cleavage; by viral protease NS3"
FT                   /evidence="ECO:0000250|UniProtKB:P29990"
FT   SITE            2501
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2504
FT                   /note="mRNA cap binding; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2505
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2507
FT                   /note="mRNA cap binding; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2512
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2516
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2548
FT                   /note="Essential for 2'-O-methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2633
FT                   /note="Essential for 2'-O-methyltransferase and N-7
FT                   methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2637
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2668
FT                   /note="Essential for 2'-O-methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2699
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2701
FT                   /note="mRNA cap binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            2704
FT                   /note="Essential for 2'-O-methyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT   SITE            3372
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         2543
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P03314"
FT   CARBOHYD        182
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        346
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        904
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        981
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        2297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        2301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        2453
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   DISULFID        147..181
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        158..193
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        166..179
FT                   /evidence="ECO:0000250|UniProtKB:P14336"
FT   DISULFID        282..309
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        339..400
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        353..384
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        371..395
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        464..564
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        581..612
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        778..789
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        829..917
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        953..997
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1054..1103
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1065..1086
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   DISULFID        1087..1090
FT                   /evidence="ECO:0000250|UniProtKB:P17763"
FT   STRAND          585..593
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          599..605
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          607..609
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          611..613
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          616..620
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          632..634
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          643..648
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          652..661
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   HELIX           662..664
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          666..671
FT                   /evidence="ECO:0007829|PDB:4AM0"
FT   STRAND          776..779
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          782..784
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          788..790
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          792..796
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   TURN            799..801
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          806..809
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           815..826
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           836..844
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           846..855
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          861..864
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           872..874
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           878..881
FT                   /evidence="ECO:0007829|PDB:8WBD"
FT   STRAND          890..895
FT                   /evidence="ECO:0007829|PDB:8WBC"
FT   STRAND          906..910
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          915..917
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           919..921
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          927..932
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          936..945
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           955..957
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          959..963
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          966..970
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          975..994
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1001..1003
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1012..1014
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1019..1021
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1025..1029
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1042..1044
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1045..1052
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1058..1061
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1065..1068
FT                   /evidence="ECO:0007829|PDB:8WBC"
FT   STRAND          1072..1075
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1077..1079
FT                   /evidence="ECO:0007829|PDB:8WBE"
FT   STRAND          1084..1089
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1095..1098
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1103..1105
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1109..1114
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   HELIX           1116..1118
FT                   /evidence="ECO:0007829|PDB:8WBB"
FT   STRAND          1395..1401
FT                   /evidence="ECO:0007829|PDB:7VMV"
FT   STRAND          1418..1433
FT                   /evidence="ECO:0007829|PDB:7VMV"
FT   STRAND          1435..1437
FT                   /evidence="ECO:0007829|PDB:7VMV"
SQ   SEQUENCE   3387 AA;  378408 MW;  83A0CECAB088E1A8 CRC64;
     MNQRKKVVRP PFNMLKRERN RVSTPQGLVK RFSTGLFSGK GPLRMVLAFI TFLRVLSIPP
     TAGILKRWGQ LKKNKAIKIL TGFRKEIGRM LNILNGRKRS TMTLLCLIPT AMAFHLSTRD
     GEPLMIVARH ERGRPLLFKT TEGINKCTLI AMDLGEMCED TVTYECPLLV NTEPEDIDCW
     CNLTSAWVMY GTCTQSGERR REKRSVALTP HSGMGLETRA ETWMSSEGAW KHAQRVESWI
     LRNPGFALLA GFMAYMIGQT GIQRTVFFVL MMLVAPSYGM RCVGVGNRDF VEGVSGGAWV
     DLVLEHGGCV TTMAQGKPTL DFELIKTTAK EVALLRTYCI EASISNITTA TRCPTQGEPY
     LKEEQDQQYI CRRDVVDRGW GNGCGLFGKG GVVTCAKFSC SGKITGNLVQ IENLEYTVVV
     TVHNGDTHAV GNDIPNHGVT ATITPRSPSV EVKLPDYGEL TLDCEPRSGI DFNEMILMKM
     KKKTWLVHKQ WFLDLPLPWA AGADTSEVHW NYKERMVTFK VPHAKRQDVT VLGSQEGAMH
     SALTGATEVD SGDGNHMFAG HLKCKVRMEK LRIKGMSYTM CSGKFSIDKE MAETQHGTTV
     VKVKYEGAGA PCKVPIEIRD VNKEKVVGRI ISSTPFAEYT NSVTNIELEP PFGDSYIVIG
     VGDSALTLHW FRKGSSIGKM LESTYRGAKR MAILGETAWD FGSVGGLLTS LGKAVHQVFG
     SVYTTMFGGV SWMVRILIGF LVLWIGTNSR NTSMAMTCIA VGGITLFLGF TVHADTGCAV
     SWSGKELKCG SGIFVIDNVH TWTEQYKFQP ESPARLASAI LNAHEDGVCG IRSTTRLENI
     MWKQITNELN YVLWEGGHDL TVVAGDVKGV LSKGKRALAP PVNDLKYSWK TWGKAKIFTP
     EAKNSTFLID GPDTSECPNE RRAWNFLEVE DYGFGMFTTN IWMKFREGSS EVCDHRLMSA
     AIKDQKAVHA DMGYWIESSK NQTWQIEKAS LIEVKTCLWP KTHTLWSNGV LESQMLIPKA
     YAGPFSQHNY RQGYATQTVG PWHLGKLEID FGECPGTTVT IQEDCDHRGP SLRTTTASGK
     LVTQWCCRSC TMPPLRFLGE DGCWYGMEIR PLSEKEENMV KSQVSAGQGT SETFSMGLLC
     LTLFVEECLR RRVTRKHMIL VVVTTLCAII LGGLTWMDLL RALIMLGDTM SGRMGGQIHL
     AIMAVFKMSP GYVLGIFLRK LTSRETALMV IGMAMTTVLS IPHDLMEFID GISLGLILLK
     MVTHFDNTQV GTLALSLTFI RSTMPLVMAW RTIMAVLFVV TLIPLCRTSC LQKQSHWVEI
     TALILGAQAL PVYLMTLMKG ASKRSWPLNE GIMAVGLVSL LGSALLKNDV PLAGPMVAGG
     LLLAAYVMSG SSADLSLEKA ANVQWDEMAD ITGSSPIIEV KQDEDGSFSI RDIEETNMIT
     LLVKLALITV SGLYPLAIPV TMTLWYMWQV KTQRSGALWD VPSPAAAQKA TLTEGVYRIM
     QRGLFGKTQV GVGIHMEGVF HTMWHVTRGS VICHETGRLE PSWADVRNDM ISYGGGWRLG
     DKWDKEEDVQ VLAIEPGKNP KHVQTKPGLF KTLTGEIGAV TLDFKPGTSG SPIINRKGKV
     IGLYGNGVVT KSGDYVSAIT QAERTGEPDY EVDEDIFRKK RLTIMDLHPG AGKTKRILPS
     IVREALKRRL RTLILAPTRV VAAEMEEALR GLPIRYQTPA VKSEHTGREI VDLMCHATFT
     TRLLSSTRVP NYNLIVMDEA HFTDPSSVAA RGYISTRVEM GEAAAIFMTA TPPGATDPFP
     QSNSPIEDIE REIPERSWNT GFDWITDYQG KTVWFVPSIK AGNDIANCLR KSGKKVIQLS
     RKTFDTEYPK TKLTDWDFVV TTDISEMGAN FRAGRVIDPR RCLKPVISTD GPERVILAGP
     IPVTPASAAQ RRGRIGRNPA QEDDQYVFSG DPLKNDEDHA HWTEAKMLLD NIYTPEGIIP
     TLFGPEREKN QAIDGEFRLR GEQRKTFVEL MRRGDLPVWL SYKVASAGIS YKDREWCFTG
     ERNNQILEEN MEVEIWTREG EKKKLRPKWL DARVYADPMA LKDFKEFASG RKSITLDILT
     EIASLPTYLS SRAKLALDNI VMLHTTERGG KAYQHALNEL PESLETLMLV ALLGAMTAGI
     FLFFMQGKGI GKLSMGLIAI AVASGLLWVA EIQPQWIAAS IILEFFLMVL LIPEPEKQRT
     PQDNQLIYVI LTILTIIGLI AANEMGLIEK TKTDFGFYQV KTETTILDVD LRPASAWTLY
     AVATTILTPM LRHTIENTSA NLSLAAIANQ AAVLMGLGKG WPLHRMDLGV PLLAMGCYSQ
     VNPTTLIASL VMLLVHYAII GPGLQAKATR EAQKRTAAGI MKNPTVDGIT VIDLEPISYD
     PKFEKQLGQV MLLVLCAGQL LLMRTTWAFC EVLTLATGPV LTLWEGNPGR FWNTTIAVST
     ANIFRGSYLA GAGLAFSLIK NAQTPRRGTG TTGETLGEKW KRQLNSLDRK EFEEYKRSGI
     LEVDRTEAKS ALKDGSKIKH AVSRGSSKIR WIVERGMVKP KGKVVDLGCG RGGWSYYMAT
     LKNVTEVKGY TKGGPGHEEP IPMATYGWNL VKLHSGVDVF YKPTEQVDTL LCDIGESSSN
     PTIEEGRTLR VLKMVEPWLS SKPEFCIKVL NPYMPTVIEE LEKLQRKHGG SLVRCPLSRN
     STHEMYWVSG VSGNIVSSVN TTSKMLLNRF TTRHRKPTYE KDVDLGAGTR SVSTETEKPD
     MTIIGRRLQR LQEEHKETWH YDQENPYRTW AYHGSYEAPS TGSASSMVNG VVKLLTKPWD
     VIPMVTQLAM TDTTPFGQQR VFKEKVDTRT PQPKPGTRMV MTTTANWLWA LLGKKKNPRL
     CTREEFISKV RSNAAIGAVF QEEQGWTSAS EAVNDSRFWE LVDKERALHQ EGKCESCVYN
     MMGKREKKLG EFGRAKGSRA IWYMWLGARF LEFEALGFLN EDHWFGRENS WSGVEGEGLH
     RLGYILEDID KKDGDLIYAD DTAGWDTRIT EDDLLNEELI TEQMAPHHKI LAKAIFKLTY
     QNKVVKVLRP TPKGAVMDII SRKDQRGSGQ VGTYGLNTFT NMEVQLIRQM EAEGVITQDD
     MHNPKGLKER VEKWLKECGV DRLKRMAISG DDCVVKPLDE RFSTSLLFLN DMGKVRKDIP
     QWEPSKGWKN WQEVPFCSHH FHKIFMKDGR SLVVPCRNQD ELIGRARISQ GAGWSLRETA
     CLGKAYAQMW SLMYFHRRDL RLASMAICSA VPTEWFPTSR TTWSIHAHHQ WMTTEDMLKV
     WNRVWIEDNP NMTDKTPVHS WEDIPYLGKR EDLWCGSLIG LSSRATWAKN IHTAITQVRN
     LIGKEEYVDY MPVMKRYSAP FESEGVL
//