ID POLG_DEN3S Reviewed; 3390 AA.
AC Q6YMS4; Q6DLV0;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 149.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C;
DE AltName: Full=Core protein;
DE Contains:
DE RecName: Full=Protein prM;
DE Contains:
DE RecName: Full=Peptide pr;
DE Contains:
DE RecName: Full=Small envelope protein M;
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE Contains:
DE RecName: Full=Non-structural protein 2A;
DE Short=NS2A;
DE Contains:
DE RecName: Full=Serine protease subunit NS2B;
DE AltName: Full=Flavivirin protease NS2B regulatory subunit;
DE AltName: Full=Non-structural protein 2B;
DE Contains:
DE RecName: Full=Serine protease NS3;
DE EC=3.4.21.91;
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Q6P4};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9Q6P4};
DE AltName: Full=Flavivirin protease NS3 catalytic subunit;
DE AltName: Full=Non-structural protein 3;
DE Contains:
DE RecName: Full=Non-structural protein 4A;
DE Short=NS4A;
DE Contains:
DE RecName: Full=Peptide 2k;
DE Contains:
DE RecName: Full=Non-structural protein 4B;
DE Short=NS4B;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase NS5;
DE EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924, ECO:0000269|PubMed:26578813};
DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924, ECO:0000269|PubMed:26578813};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539, ECO:0000269|PubMed:24025331};
DE AltName: Full=Non-structural protein 5;
GN Name=pol;
OS Dengue virus type 3 (strain Sri Lanka/1266/2000) (DENV-3).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Orthoflavivirus; Orthoflavivirus denguei;
OC Dengue virus.
OX NCBI_TaxID=408692;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RA Lim S.P., Ooi E.E., Vasudevan S.G.;
RT "Full length genomic sequence of a Dengue virus of serotype 3 from
RT Singapore.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 2762-3390 IN COMPLEX WITH GTP AND
RP ZINC.
RX PubMed=17301146; DOI=10.1128/jvi.02283-06;
RA Yap T.L., Xu T., Chen Y.L., Malet H., Egloff M.P., Canard B.,
RA Vasudevan S.G., Lescar J.;
RT "Crystal structure of the dengue virus RNA-dependent RNA polymerase
RT catalytic domain at 1.85-angstrom resolution.";
RL J. Virol. 81:4753-4765(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2753-3390 IN COMPLEX WITH ZINC,
RP CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE NS5), AND SUBUNIT
RP (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=24025331; DOI=10.1074/jbc.m113.508606;
RA Lim S.P., Koh J.H., Seh C.C., Liew C.W., Davidson A.D., Chua L.S.,
RA Chandrasekaran R., Cornvik T.C., Shi P.Y., Lescar J.;
RT "A crystal structure of the dengue virus non-structural protein 5 (NS5)
RT polymerase delineates interdomain amino acid residues that enhance its
RT thermostability and de novo initiation activities.";
RL J. Biol. Chem. 288:31105-31114(2013).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2496-3385, CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE NS5), MUTAGENESIS OF ARG-2528; LYS-2532;
RP ARG-2547; LYS-2551; ARG-2574; GLU-2601; ASP-2636; LYS-2670; ARG-2701 AND
RP GLU-2706, AND ACTIVE SITE (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=26578813; DOI=10.1073/pnas.1514978112;
RA Zhao Y., Soh T.S., Lim S.P., Chung K.Y., Swaminathan K., Vasudevan S.G.,
RA Shi P.Y., Lescar J., Luo D.;
RT "Molecular basis for specific viral RNA recognition and 2'-O-ribose
RT methylation by the dengue virus nonstructural protein 5 (NS5).";
RL Proc. Natl. Acad. Sci. U.S.A. 112:14834-14839(2015).
CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding
CC to the cell membrane and gathering the viral RNA into a nucleocapsid
CC that forms the core of a mature virus particle. During virus entry, may
CC induce genome penetration into the host cytoplasm after hemifusion
CC induced by the surface proteins. Can migrate to the cell nucleus where
CC it modulates host functions. Overcomes the anti-viral effects of host
CC EXOC1 by sequestering and degrading the latter through the proteasome
CC degradation pathway. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering
CC with host Dicer. {ECO:0000250|UniProtKB:P03314}.
CC -!- FUNCTION: [Peptide pr]: Prevents premature fusion activity of envelope
CC proteins in trans-Golgi by binding to envelope protein E at pH6.0.
CC After virion release in extracellular space, gets dissociated from E
CC dimers. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Protein prM]: Acts as a chaperone for envelope protein E
CC during intracellular virion assembly by masking and inactivating
CC envelope protein E fusion peptide. prM is the only viral peptide
CC matured by host furin in the trans-Golgi network probably to avoid
CC catastrophic activation of the viral fusion activity in acidic Golgi
CC compartment prior to virion release. prM-E cleavage is inefficient, and
CC many virions are only partially matured. These uncleaved prM would play
CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding.
CC Exerts cytotoxic effects by activating a mitochondrial apoptotic
CC pathway through M ectodomain. May display a viroporin activity.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and
CC mediates fusion between viral and cellular membranes. Envelope protein
CC is synthesized in the endoplasmic reticulum in the form of heterodimer
CC with protein prM. They play a role in virion budding in the ER, and the
CC newly formed immature particle is covered with 60 spikes composed of
CC heterodimer between precursor prM and envelope protein E. The virion is
CC transported to the Golgi apparatus where the low pH causes dissociation
CC of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is
CC inefficient, and many virions are only partially matured. These
CC uncleaved prM would play a role in immune evasion.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 1]: Disrupts the host endothelial
CC glycocalyx layer of host pulmonary microvascular endothelial cells,
CC inducing degradation of sialic acid and shedding of heparan sulfate
CC proteoglycans. NS1 induces expression of sialidases, heparanase, and
CC activates cathepsin L, which activates heparanase via enzymatic
CC cleavage. These effects are probably linked to the endothelial
CC hyperpermeability observed in severe dengue disease.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host immune response. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the
CC serine protease function of NS3. May have membrane-destabilizing
CC activity and form viroporins (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.
CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities:
CC serine protease, NTPase and RNA helicase. NS3 serine protease, in
CC association with NS2B, performs its autocleavage and cleaves the
CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-
CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and
CC unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC during unwinding. Plays a role in the inhibition of the host innate
CC immune response. Interacts with host MAVS and thereby prevents the
CC interaction between 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 NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O
CC positions. Besides its role in RNA genome replication, also prevents
CC the establishment of cellular antiviral state by blocking the
CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host
CC TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-
CC STAT signaling pathway. {ECO:0000250|UniProtKB:P17763}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of
CC the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.;
CC EC=3.4.21.91;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:24025331};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924, ECO:0000269|PubMed:26578813};
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924,
CC ECO:0000269|PubMed:26578813};
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 (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi (By similarity). Interacts with protein prM. Interacts with
CC non-structural protein 1 (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (By similarity). Interacts with envelope protein E (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3 (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3 (By similarity). May form homooligomers (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B.
CC Interacts with NS4B (By similarity). Interacts with unphosphorylated
CC RNA-directed RNA polymerase NS5; this interaction stimulates RNA-
CC directed RNA polymerase NS5 guanylyltransferase activity (By
CC similarity). Interacts with host SHFL (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with host MAVS; this
CC interaction inhibits the synthesis of IFN-beta (By similarity).
CC Interacts with host SHFL (By similarity). Interacts with host AUP1; the
CC interaction occurs in the presence of Dengue virus NS4B and induces
CC lipophagy which facilitates production of virus progeny particles (By
CC 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 NS5]: Homodimer
CC (PubMed:24025331). 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. Interacts with
CC serine protease NS3. {ECO:0000269|PubMed:24025331}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane;
CC Peripheral membrane protein; Lumenal side
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC reticulum membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane
CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side
CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently
CC associated to serine protease subunit NS2B. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles
CC hosting the replication complex. Interacts with host MAVS in the
CC mitochondrion-associated endoplasmic reticulum membranes.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex.
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase NS5]: Host
CC endoplasmic reticulum membrane; Peripheral membrane protein;
CC Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}.
CC Note=Located in RE-associated vesicles hosting the replication complex.
CC NS5 protein is mainly localized in the nucleus rather than in ER
CC vesicles, especially in the DENV 2, 3, 4 serotypes.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: The transmembrane domains of the small envelope protein M and
CC envelope protein E contain an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC mature proteins. Cleavages in the lumen of endoplasmic reticulum are
CC performed by host signal peptidase, whereas cleavages in the
CC cytoplasmic side are performed by serine protease NS3. Signal cleavage
CC at the 2K-4B site requires a prior NS3 protease-mediated cleavage at
CC the 4A-2K site. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin,
CC releasing the mature small envelope protein M, and peptide pr. This
CC cleavage is incomplete as up to 30% of viral particles still carry
CC uncleaved prM. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Envelope protein E]: N-glycosylated.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is
CC glycosylated and this is required for efficient secretion of the
CC protein from infected cells. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Sumoylation of RNA-directed RNA
CC polymerase NS5 increases NS5 protein stability allowing proper viral
CC RNA replication. {ECO:0000250|UniProtKB:P29990}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Phosphorylated on serines
CC residues. This phosphorylation may trigger NS5 nuclear localization.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. mRNA cap 0-1 NS5-type
CC methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}.
CC -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue";
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DR EMBL; AY099336; AAM51537.1; -; Genomic_RNA.
DR EMBL; AY662691; AAT75224.1; -; Genomic_RNA.
DR RefSeq; YP_001621843.1; NC_001475.2.
DR PDB; 2J7U; X-ray; 1.85 A; A=2762-3390.
DR PDB; 2J7W; X-ray; 2.60 A; A=2763-3390.
DR PDB; 3VWS; X-ray; 2.10 A; A=2762-3390.
DR PDB; 4C11; X-ray; 2.60 A; A/B=2753-3390.
DR PDB; 4HHJ; X-ray; 1.79 A; A=2762-3390.
DR PDB; 5DTO; X-ray; 2.60 A; A=2496-3385.
DR PDB; 5EIW; X-ray; 1.61 A; A/C=2491-2766.
DR PDB; 5F3T; X-ray; 2.05 A; A=2762-3390.
DR PDB; 5F3Z; X-ray; 2.00 A; A=2762-3390.
DR PDB; 5F41; X-ray; 2.00 A; A=2762-3390.
DR PDB; 5HMW; X-ray; 2.15 A; A=2762-3390.
DR PDB; 5HMX; X-ray; 2.40 A; A=2762-3390.
DR PDB; 5HMY; X-ray; 2.10 A; A=2762-3390.
DR PDB; 5HMZ; X-ray; 1.99 A; A=2762-3390.
DR PDB; 5HN0; X-ray; 2.05 A; A=2762-3390.
DR PDB; 5I3P; X-ray; 2.45 A; A=2762-3390.
DR PDB; 5I3Q; X-ray; 1.88 A; A=2762-3390.
DR PDB; 5IQ6; X-ray; 3.00 A; A=2763-3390.
DR PDB; 5JJR; X-ray; 1.99 A; A=2494-3385.
DR PDB; 5JJS; X-ray; 1.65 A; A=2494-3385.
DR PDB; 5WJN; X-ray; 2.85 A; C/F/I=1606-1615.
DR PDB; 5WKH; X-ray; 3.20 A; C/H=1606-1615.
DR PDB; 6H80; X-ray; 2.30 A; A=2762-3390.
DR PDB; 6H9R; X-ray; 2.40 A; A=2762-3390.
DR PDB; 6XD0; X-ray; 2.01 A; A=2762-3390.
DR PDB; 6XD1; X-ray; 1.95 A; A=2762-3390.
DR PDBsum; 2J7U; -.
DR PDBsum; 2J7W; -.
DR PDBsum; 3VWS; -.
DR PDBsum; 4C11; -.
DR PDBsum; 4HHJ; -.
DR PDBsum; 5DTO; -.
DR PDBsum; 5EIW; -.
DR PDBsum; 5F3T; -.
DR PDBsum; 5F3Z; -.
DR PDBsum; 5F41; -.
DR PDBsum; 5HMW; -.
DR PDBsum; 5HMX; -.
DR PDBsum; 5HMY; -.
DR PDBsum; 5HMZ; -.
DR PDBsum; 5HN0; -.
DR PDBsum; 5I3P; -.
DR PDBsum; 5I3Q; -.
DR PDBsum; 5IQ6; -.
DR PDBsum; 5JJR; -.
DR PDBsum; 5JJS; -.
DR PDBsum; 5WJN; -.
DR PDBsum; 5WKH; -.
DR PDBsum; 6H80; -.
DR PDBsum; 6H9R; -.
DR PDBsum; 6XD0; -.
DR PDBsum; 6XD1; -.
DR SMR; Q6YMS4; -.
DR BindingDB; Q6YMS4; -.
DR MEROPS; S07.001; -.
DR GlyCosmos; Q6YMS4; 10 sites, No reported glycans.
DR ABCD; Q6YMS4; 1 sequenced antibody.
DR GeneID; 5075727; -.
DR KEGG; vg:5075727; -.
DR BRENDA; 2.7.7.48; 1867.
DR BRENDA; 3.4.21.91; 9648.
DR PRO; PR:Q6YMS4; -.
DR Proteomes; UP000007537; Segment.
DR Proteomes; UP000096981; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-dependent 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:0039574; P:disruption by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; 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 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.
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; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR NCBIfam; TIGR04240; flavi_E_stem; 1.
DR Pfam; PF20907; Flav_NS3-hel_C; 1.
DR Pfam; PF01003; Flavi_capsid; 1.
DR Pfam; PF07652; Flavi_DEAD; 1.
DR Pfam; PF21659; Flavi_E_stem; 1.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF00948; Flavi_NS1; 1.
DR Pfam; PF01005; Flavi_NS2A; 1.
DR Pfam; PF01002; Flavi_NS2B; 1.
DR Pfam; PF01350; Flavi_NS4A; 1.
DR Pfam; PF01349; Flavi_NS4B; 1.
DR Pfam; PF00972; Flavi_NS5; 1.
DR Pfam; PF20483; Flavi_NS5_thumb; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF00949; Peptidase_S7; 1.
DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF81296; E set domains; 1.
DR SUPFAM; SSF101257; Flavivirus capsid protein C; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR SUPFAM; SSF56983; Viral glycoprotein, central and dimerisation domains; 1.
DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1.
DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 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;
KW Suppressor of RNA silencing; Transcription; Transcription regulation;
KW Transferase; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Viral attachment to host cell; Viral envelope protein;
KW 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_0000405225"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268088"
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_0000268089"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268090"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268091"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268092"
FT CHAIN 281..773
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268093"
FT CHAIN 774..1125
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268094"
FT CHAIN 1126..1343
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268095"
FT CHAIN 1344..1473
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268097"
FT CHAIN 1474..2092
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268098"
FT CHAIN 2093..2219
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268099"
FT PEPTIDE 2220..2242
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268100"
FT CHAIN 2243..2490
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268101"
FT CHAIN 2491..3390
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000268102"
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"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1396..1435
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1658..1661
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT MOTIF 1758..1761
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2567..2570
FT /note="SUMO-interacting motif"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT ACT_SITE 1524
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1548
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1608
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2551
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:26578813"
FT ACT_SITE 2636
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:26578813"
FT ACT_SITE 2670
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:26578813"
FT ACT_SITE 2706
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:26578813"
FT BINDING 1667..1674
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2546
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2576
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2577
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2594
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2595
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2621
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2622
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2637
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2708
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2927
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 2931
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 2936
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 2939
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 3202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 3218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17301146"
FT BINDING 3337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17301146"
FT SITE 100..101
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 205..206
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT SITE 280..281
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 773..774
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1125..1126
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1343..1344
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1473..1474
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1931
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1934
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2092..2093
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2219..2220
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2242..2243
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2490..2491
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2504
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2507
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2508
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2510
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2515
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2519
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2551
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2636
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2640
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2670
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2701
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2703
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2706
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|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 283..310
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 340..401
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 354..385
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 372..396
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 463..563
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 580..611
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 777..788
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 828..916
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 952..996
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1053..1102
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1064..1086
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1085..1089
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT VARIANT 97
FT /note="Q -> K"
FT VARIANT 684
FT /note="E -> A"
FT VARIANT 867
FT /note="L -> I"
FT VARIANT 1006
FT /note="T -> S"
FT VARIANT 1148
FT /note="L -> M"
FT VARIANT 1252
FT /note="V -> I"
FT VARIANT 1400
FT /note="P -> A"
FT VARIANT 1585
FT /note="T -> M"
FT VARIANT 1871
FT /note="T -> S"
FT VARIANT 2063
FT /note="K -> R"
FT VARIANT 2128
FT /note="D -> H"
FT VARIANT 2239
FT /note="T -> I"
FT VARIANT 2399
FT /note="S -> P"
FT VARIANT 2402
FT /note="F -> Y"
FT VARIANT 2856
FT /note="M -> L"
FT VARIANT 2862
FT /note="A -> V"
FT VARIANT 2864
FT /note="E -> G"
FT VARIANT 2970
FT /note="A -> V"
FT VARIANT 3093
FT /note="L -> V"
FT MUTAGEN 2528
FT /note="R->A: 90% loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2532
FT /note="K->A: 25% loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2547
FT /note="R->A: Complete loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2551
FT /note="K->A: Complete loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2574
FT /note="R->A: 40% loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2601
FT /note="E->R: Complete loss of 2'-O-MTase activity.
FT Decreased thermostability both in the presence and absence
FT of the RNA ligand."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2636
FT /note="D->A: Complete loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2670
FT /note="K->A: Complete loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2701
FT /note="R->A: 98% loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT MUTAGEN 2706
FT /note="E->A: Complete loss of 2'-O-MTase activity."
FT /evidence="ECO:0000269|PubMed:26578813"
FT HELIX 2499..2509
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2512..2519
FT /evidence="ECO:0007829|PDB:5EIW"
FT TURN 2520..2522
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2524..2527
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2529..2536
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2548..2557
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2565..2570
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2576..2581
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2587..2593
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2611..2613
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2614..2617
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2622..2624
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2631..2635
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2644..2658
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2659..2661
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2666..2672
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2677..2690
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2693..2695
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2707..2712
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2717..2730
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2733..2735
FT /evidence="ECO:0007829|PDB:5EIW"
FT STRAND 2740..2743
FT /evidence="ECO:0007829|PDB:5EIW"
FT HELIX 2754..2756
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2763..2776
FT /evidence="ECO:0007829|PDB:5JJS"
FT TURN 2777..2780
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 2790..2800
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2812..2816
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2819..2823
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2825..2830
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2837..2847
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2857..2874
FT /evidence="ECO:0007829|PDB:5JJS"
FT TURN 2875..2877
FT /evidence="ECO:0007829|PDB:5IQ6"
FT HELIX 2885..2893
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2909..2916
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2918..2932
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 2941..2944
FT /evidence="ECO:0007829|PDB:4HHJ"
FT TURN 2951..2956
FT /evidence="ECO:0007829|PDB:6XD1"
FT HELIX 2961..2978
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2980..2983
FT /evidence="ECO:0007829|PDB:5JJS"
FT TURN 2984..2987
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 2989..2992
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 2993..2995
FT /evidence="ECO:0007829|PDB:5JJS"
FT TURN 2997..2999
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3001..3012
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3014..3017
FT /evidence="ECO:0007829|PDB:4HHJ"
FT HELIX 3027..3030
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3033..3039
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3040..3045
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3048..3060
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3063..3073
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3076..3087
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3090..3092
FT /evidence="ECO:0007829|PDB:5HMZ"
FT HELIX 3095..3114
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3120..3124
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3131..3145
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3148..3151
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3154..3157
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3162..3166
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3169..3173
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3178..3181
FT /evidence="ECO:0007829|PDB:5F41"
FT STRAND 3190..3192
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3193..3195
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3201..3207
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3213..3218
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3221..3228
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3230..3234
FT /evidence="ECO:0007829|PDB:4HHJ"
FT HELIX 3238..3255
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3260..3272
FT /evidence="ECO:0007829|PDB:5JJS"
FT STRAND 3294..3297
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3299..3307
FT /evidence="ECO:0007829|PDB:5JJS"
FT TURN 3308..3310
FT /evidence="ECO:0007829|PDB:5F41"
FT HELIX 3323..3325
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3331..3336
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3344..3364
FT /evidence="ECO:0007829|PDB:5JJS"
FT HELIX 3373..3375
FT /evidence="ECO:0007829|PDB:5HMY"
SQ SEQUENCE 3390 AA; 377923 MW; 14C0E2C0C9189CCB CRC64;
MNNQRKKTGK PSINMLKRVR NRVSTGSQLA KRFSKGLLNG QGPMKLVMAF IAFLRFLAIP
PTAGVLARWG TFKKSGAIKV LKGFKKEISN MLSIINQRKK TSLCLMMILP AALAFHLTSR
DGEPRMIVGK NERGKSLLFK TASGINMCTL IAMDLGEMCD DTVTYKCPHI TEVEPEDIDC
WCNLTSTWVT YGTCNQAGEH 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 FFDLPLPWAS GATTETPTWN RKELLVTFKN AHAKKQEVVV LGSQEGAMHT
ALTGATEIQN SGGTSIFAGH LKCRLKMDKL ELKGMSYAMC TNTFVLKKEV SETQHGTILI
KVEYKGEDAP CKIPFSTEDG QGKAHNGRLI TANPVVTKKE EPVNIEAEPP FGESNIVIGI
GDNALKINWY KKGSSIGKMF EATERGARRM AILGDTAWDF GSVGGVLNSL GKMVHQIFGS
AYTALFSGVS WVMKIGIGVL LTWIGLNSKN TSMSFSCIAI GIITLYLGAV VQADMGCVIN
WKGKELKCGS GIFVTNEVHT WTEQYKFQAD SPKRLATAIA GAWENGVCGI RSTTRMENLL
WKQIANELNY ILWENNIKLT VVVGDTLGVL EQGKRTLTPQ PMELKYSWKT WGKAKIVTAE
TQNSSFIIDG PNTPECPSAS RAWNVWEVED YGFGVFTTNI WLKLREVYTQ LCDHRLMSAA
VKDERAVHAD MGYWIESQKN GSWKLEKASL IEVKTCTWPK SHTLWTNGVL ESDMIIPKSL
AGPISQHNYR PGYHTQTAGP WHLGKLELDF NYCEGTTVVI TESCGTRGPS LRTTTVSGKL
IHEWCCRSCT LPPLRYMGED GCWYGMEIRP ISEKEENMVK SLVSAGSGKV DNFTMGVLCL
AILFEEVLRG KFGKKHMIAG VFFTFVLLLS GQITWRDMAH TLIMIGSNAS DRMGMGVTYL
ALIATFKIQP FLALGFFLRK LTSRENLLLG VGLAMATTLQ LPEDIEQMAN GVALGLMALK
LITQFETYQL WTALVSLTCS NTIFTLTVAW RTATLILAGV SLLPVCQSSS MRKTDWLPMT
VAAMGVPPLP LFIFSLKDTL KRRSWPLNEG VMAVGLVSIL ASSLLRNDVP MAGPLVAGGL
LIACYVITGT SADLTVEKAP DVTWEEEAEQ TGVSHNLMIT VDDDGTMRIK DDETENILTV
LLKTALLIVS GIFPYSIPAT LLVWHTWQKQ TQRSGVLWDV PSPPETQKAE LEEGVYRIKQ
QGIFGKTQVG VGVQKEGVFH TMWHVTRGAV LTHNGKRLEP NWASVKKDLI SYGGGWRLSA
QWQKGEEVQV IAVEPGKNPK NFQTTPGTFQ 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 VMLHTSEDGG RAYRHAVEEL PETMETLLLL GLMILLTGGA
MLFLISGKGI GKTSIGLICV IASSGMLWMA EVPLQWIASA IVLEFFMMVL LIPEPEKQRT
PQDNQLAYVV IGILTLAATI AANEMGLLET TKRDLGMSKE PGVVSPTSYL DVDLHPASAW
TLYAVATTVI TPMLRHTIEN STANVSLAAI ANQAVVLMGL DKGWPISKMD LGVPLLALGC
YSQVNPLTLT AAVLLLITHY AIIGPGLQAK ATREAQKRTA AGIMKNPTVD GIMTIDLDSV
IFDSKFEKQL GQVMLLVLCA VQLLLMRTSW ALCEALTLAT GPITTLWEGS PGKFWNTTIA
VSMANIFRGS YLAGAGLAFS IMKSVGTGKR GTGSQGETLG EKWKKKLNQL SRKEFDLYKK
SGITEVDRTE AKEGLKRGET THHAVSRGSA KLQWFVERNM VVPEGRVIDL GCGRGGWSYY
CAGLKKVTEV RGYTKGGPGH EEPVPMSTYG WNIVKLMSGK DVFYLPPEKC DTLLCDIGES
SPSPTVEESR TIRVLKMVEP WLKNNQFCIK VLNPYMPTVI EHLERLQRKH GGMLVRNPLS
RNSTHEMYWI SNGTGNIVSS VNMVSRLLLN RFTMTHRRPT IEKDVDLGAG TRHVNAEPET
PNMDVIGERI KRIKEEHNST WHYDDENPYK TWAYHGSYEV KATGSASSMI NGVVKLLTKP
WDVVPMVTQM AMTDTTPFGQ QRVFKEKVDT RTPRPMPGTR KAMEITAEWL WRTLGRNKRP
RLCTREEFTK KVRTNAAMGA VFTEENQWDS AKAAVEDEEF WKLVDREREL HKLGKCGSCV
YNMMGKREKK LGEFGKAKGS RAIWYMWLGA RYLEFEALGF LNEDHWFSRE NSYSGVEGEG
LHKLGYILRD ISKIPGGAMY ADDTAGWDTR ITEDDLHNEE KIIQQMDPEH RQLANAIFKL
TYQNKVVKVQ RPTPTGTVMD IISRKDQRGS GQLGTYGLNT FTNMEAQLVR QMEGEGVLTK
ADLENPHLLE KKITQWLETK GVERLKRMAI SGDDCVVKPI DDRFANALLA LNDMGKVRKD
IPQWQPSKGW HDWQQVPFCS HHFHELIMKD GRKLVVPCRP QDELIGRARI SQGAGWSLRE
TACLGKAYAQ MWSLMYFHRR DLRLASNAIC SAVPVHWVPT SRTTWSIHAH HQWMTTEDML
TVWNRVWIEE NPWMEDKTPV TTWENVPYLG KREDQWCGSL IGLTSRATWA QNIPTAIQQV
RSLIGNEEFL DYMPSMKRFR KEEESEGAIW
//
