POLG_DEN2P
ID POLG_DEN2P Reviewed; 3388 AA.
AC P12823; Q88646; Q88647; Q88648; Q88649; Q88650; Q88651; Q88652; Q88653;
AC Q88654; Q88655;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 207.
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};
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 2 (strain Puerto Rico/PR159-S1/1969) (DENV-2).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11066;
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=2827375; DOI=10.1016/0042-6822(88)90406-0;
RA Hahn Y.S., Galler R., Hunkapiller T., Dalrymple J.M., Strauss J.H.,
RA Strauss E.G.;
RT "Nucleotide sequence of dengue 2 RNA and comparison of the encoded proteins
RT with those of other flaviviruses.";
RL Virology 162:167-180(1988).
RN [2]
RP C-TERMINUS (CAPSID PROTEIN C), C-TERMINUS (ENVELOPE PROTEIN E), AND
RP C-TERMINUS (NON-STRUCTURAL PROTEIN 1).
RC STRAIN=New-Guinea;
RX PubMed=2741348; DOI=10.1016/0042-6822(89)90510-2;
RA Wright P.J., Cauchi M.R., Ng M.L.;
RT "Definition of the carboxy termini of the three glycoproteins specified by
RT dengue virus type 2.";
RL Virology 171:61-67(1989).
RN [3]
RP DISULFIDE BOND (NON-STRUCTURAL PROTEIN 1).
RX PubMed=14981082; DOI=10.1074/jbc.m312907200;
RA Wallis T.P., Huang C.Y., Nimkar S.B., Young P.R., Gorman J.J.;
RT "Determination of the disulfide bond arrangement of dengue virus NS1
RT protein.";
RL J. Biol. Chem. 279:20729-20741(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2494-2783 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, AND CHARACTERIZATION OF METHYLTRANSFERASE
RP ACTIVITY (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=12032088; DOI=10.1093/emboj/21.11.2757;
RA Egloff M.P., Benarroch D., Selisko B., Romette J.L., Canard B.;
RT "An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA
RT polymerase NS5: crystal structure and functional characterization.";
RL EMBO J. 21:2757-2768(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 281-674, AND DISULFIDE BONDS
RP (ENVELOPE PROTEIN E).
RX PubMed=12759475; DOI=10.1073/pnas.0832193100;
RA Modis Y., Ogata S., Clements D., Harrison S.C.;
RT "A ligand-binding pocket in the dengue virus envelope glycoprotein.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6986-6991(2003).
RN [6]
RP STRUCTURE BY ELECTRON MICROSCOPY (16 ANGSTROMS) OF IMMATURE PARTICLES
RP (SMALL ENVELOPE PROTEIN M, AND ENVELOPE PROTEIN E).
RX PubMed=12773377; DOI=10.1093/emboj/cdg270;
RA Zhang Y., Corver J., Chipman P.R., Zhang W., Pletnev S.V., Sedlak D.,
RA Baker T.S., Strauss J.H., Kuhn R.J., Rossmann M.G.;
RT "Structures of immature flavivirus particles.";
RL EMBO J. 22:2604-2613(2003).
CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding
CC to the cell membrane and gathering the viral RNA into a nucleocapsid
CC that forms the core of a mature virus particle. During virus entry, may
CC induce genome penetration into the host cytoplasm after hemifusion
CC induced by the surface proteins. Can migrate to the cell nucleus where
CC it modulates host functions. Overcomes the anti-viral effects of host
CC EXOC1 by sequestering and degrading the latter through the proteasome
CC degradation pathway. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering
CC with host Dicer. {ECO:0000250|UniProtKB:P03314}.
CC -!- FUNCTION: [Peptide pr]: Prevents premature fusion activity of envelope
CC proteins in trans-Golgi by binding to envelope protein E at pH6.0.
CC After virion release in extracellular space, gets dissociated from E
CC dimers. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Protein prM]: Acts as a chaperone for envelope protein E
CC during intracellular virion assembly by masking and inactivating
CC envelope protein E fusion peptide. prM is the only viral peptide
CC matured by host furin in the trans-Golgi network probably to avoid
CC catastrophic activation of the viral fusion activity in acidic Golgi
CC compartment prior to virion release. prM-E cleavage is inefficient, and
CC many virions are only partially matured. These uncleaved prM would play
CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding.
CC Exerts cytotoxic effects by activating a mitochondrial apoptotic
CC pathway through M ectodomain. May display a viroporin activity.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and
CC mediates fusion between viral and cellular membranes. Envelope protein
CC is synthesized in the endoplasmic reticulum in the form of heterodimer
CC with protein prM. They play a role in virion budding in the ER, and the
CC newly formed immature particle is covered with 60 spikes composed of
CC heterodimer between precursor prM and envelope protein E. The virion is
CC transported to the Golgi apparatus where the low pH causes dissociation
CC of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is
CC inefficient, and many virions are only partially matured. These
CC uncleaved prM would play a role in immune evasion.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 1]: Disrupts the host endothelial
CC glycocalyx layer of host pulmonary microvascular endothelial cells,
CC inducing degradation of sialic acid and shedding of heparan sulfate
CC proteoglycans. NS1 induces expression of sialidases, heparanase, and
CC activates cathepsin L, which activates heparanase via enzymatic
CC cleavage. These effects are probably linked to the endothelial
CC hyperpermeability observed in severe dengue disease.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host immune response. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the
CC serine protease function of NS3. May have membrane-destabilizing
CC activity and form viroporins (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.
CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities:
CC serine protease, NTPase and RNA helicase. NS3 serine protease, in
CC association with NS2B, performs its autocleavage and cleaves the
CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-
CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and
CC unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC during unwinding. Plays a role in the inhibition of the host innate
CC immune response. Interacts with host MAVS and thereby prevents the
CC interaction between DDX58 and MAVS. In turn, IFN-beta production is
CC impaired. Interacts with host AUP1 which mediates induction of
CC lipophagy in host cells and facilitates production of virus progeny
CC particles (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29991, ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC required for the interferon antagonism activity of the latter.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-
CC derived membrane vesicles where the viral replication takes place.
CC Inhibits interferon (IFN)-induced host STAT1 phosphorylation and
CC nuclear translocation, thereby preventing the establishment of cellular
CC antiviral state by blocking the IFN-alpha/beta pathway.
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O
CC positions. Besides its role in RNA genome replication, also prevents
CC the establishment of cellular antiviral state by blocking the
CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host
CC TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-
CC STAT signaling pathway (By similarity). May reduce immune responses by
CC preventing the recruitment of the host PAF1 complex to interferon-
CC responsive genes (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29990}.
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 -!- 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:
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};
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 + 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 -!- SUBUNIT: [Capsid protein C]: Homodimer. Interacts (via N-terminus) with
CC host EXOC1 (via C-terminus); this interaction results in EXOC1
CC degradation through the proteasome degradation pathway.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi. Interacts with protein prM. Interacts with non-structural
CC protein 1. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3. May form homooligomers.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B.
CC Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA
CC polymerase NS5; this interaction stimulates RNA-directed RNA polymerase
CC NS5 guanylyltransferase activity. Interacts with host SHFL.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with host MAVS; this
CC interaction inhibits the synthesis of IFN-beta. Interacts with host
CC SHFL (By similarity). Interacts with host AUP1; the interaction occurs
CC in the presence of Dengue virus NS4B and induces lipophagy which
CC facilitates production of virus progeny particles (By similarity). May
CC interact with host SRPRA and SEC61G (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:P29990,
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 (By similarity).
CC Interacts with host STAT2; this interaction inhibits the
CC phosphorylation of the latter, and, when all viral proteins are present
CC (polyprotein), targets STAT2 for degradation (By similarity). Interacts
CC with serine protease NS3 (By similarity). Interacts with host PAF1
CC complex; the interaction may prevent the recruitment of the PAF1
CC complex to interferon-responsive genes, and thus reduces the immune
CC response (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29990}.
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 Particle ExploreR db; Note=Icosahedral capsid
CC structure;
CC URL="https://viperdb.scripps.edu/Info_Page.php?VDB=1p58";
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; M19197; AAA42962.1; -; Genomic_RNA.
DR PIR; A29972; GNWVDP.
DR PDB; 1L9K; X-ray; 2.40 A; A=2492-2784.
DR PDB; 1OAN; X-ray; 2.75 A; A/B=281-674.
DR PDB; 1OK8; X-ray; 2.00 A; A=281-674.
DR PDB; 1OKE; X-ray; 2.40 A; A/B=281-674.
DR PDB; 1P58; EM; 9.50 A; A/B/C=281-775, D/E/F=206-280.
DR PDB; 1R6A; X-ray; 2.60 A; A=2492-2784.
DR PDB; 1R6R; NMR; -; A/B=1-100.
DR PDB; 1THD; EM; 9.50 A; A/B/C=281-675.
DR PDB; 2P1D; X-ray; 2.90 A; A=2492-2784.
DR PDB; 2P3L; X-ray; 2.20 A; A=2492-2784.
DR PDB; 2P3O; X-ray; 2.76 A; A=2492-2784.
DR PDB; 2P3Q; X-ray; 2.75 A; A=2492-2784.
DR PDB; 2P40; X-ray; 2.70 A; A=2492-2784.
DR PDB; 2P41; X-ray; 1.80 A; A=2492-2784.
DR PDB; 3J8D; EM; 26.00 A; G/H/I=281-674.
DR PDB; 3ZKO; EM; 13.70 A; A/B/C=281-775.
DR PDB; 4M9F; X-ray; 2.70 A; A=1394-1440, A=1476-1660.
DR PDB; 4M9I; X-ray; 2.40 A; A=1394-1440, A=1476-1660.
DR PDB; 4M9K; X-ray; 1.46 A; A=1394-1440, A=1476-1660.
DR PDB; 4M9M; X-ray; 1.53 A; A=1394-1440, A=1476-1660.
DR PDB; 4M9T; X-ray; 1.74 A; A=1394-1440, A=1476-1660.
DR PDB; 5HHG; X-ray; 2.20 A; C=3353-3388.
DR PDBsum; 1L9K; -.
DR PDBsum; 1OAN; -.
DR PDBsum; 1OK8; -.
DR PDBsum; 1OKE; -.
DR PDBsum; 1P58; -.
DR PDBsum; 1R6A; -.
DR PDBsum; 1R6R; -.
DR PDBsum; 1THD; -.
DR PDBsum; 2P1D; -.
DR PDBsum; 2P3L; -.
DR PDBsum; 2P3O; -.
DR PDBsum; 2P3Q; -.
DR PDBsum; 2P40; -.
DR PDBsum; 2P41; -.
DR PDBsum; 3J8D; -.
DR PDBsum; 3ZKO; -.
DR PDBsum; 4M9F; -.
DR PDBsum; 4M9I; -.
DR PDBsum; 4M9K; -.
DR PDBsum; 4M9M; -.
DR PDBsum; 4M9T; -.
DR PDBsum; 5HHG; -.
DR BMRB; P12823; -.
DR SMR; P12823; -.
DR BindingDB; P12823; -.
DR ChEMBL; CHEMBL3308998; -.
DR DrugBank; DB00811; Ribavirin.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR MEROPS; S07.001; -.
DR PRIDE; P12823; -.
DR ABCD; P12823; 9 sequenced antibodies.
DR BRENDA; 2.1.1.57; 1867.
DR EvolutionaryTrace; P12823; -.
DR PRO; PR:P12823; -.
DR Proteomes; UP000007197; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd20761; capping_2-OMTase_Flaviviridae; 1.
DR CDD; cd12149; Flavi_E_C; 1.
DR DisProt; DP01245; -.
DR Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 2.60.260.50; -; 1.
DR Gene3D; 2.60.40.350; -; 1.
DR Gene3D; 2.60.98.10; -; 1.
DR Gene3D; 3.30.387.10; -; 1.
DR Gene3D; 3.30.67.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011492; DEAD_Flavivir.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR001122; Flavi_capsidC.
DR InterPro; IPR037172; Flavi_capsidC_sf.
DR InterPro; IPR027287; Flavi_E_Ig-like.
DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR InterPro; IPR001157; Flavi_NS1.
DR InterPro; IPR000752; Flavi_NS2A.
DR InterPro; IPR000487; Flavi_NS2B.
DR InterPro; IPR000404; Flavi_NS4A.
DR InterPro; IPR001528; Flavi_NS4B.
DR InterPro; IPR002535; Flavi_propep.
DR InterPro; IPR038688; Flavi_propep_sf.
DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR InterPro; IPR001850; Flavivirus_NS3_S7.
DR InterPro; IPR014412; Gen_Poly_FLV.
DR InterPro; IPR011998; Glycoprot_cen/dimer.
DR InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01003; Flavi_capsid; 1.
DR Pfam; PF07652; Flavi_DEAD; 1.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF00948; Flavi_NS1; 1.
DR Pfam; PF01005; Flavi_NS2A; 1.
DR Pfam; PF01002; Flavi_NS2B; 1.
DR Pfam; PF01350; Flavi_NS4A; 1.
DR Pfam; PF01349; Flavi_NS4B; 1.
DR Pfam; PF00972; Flavi_NS5; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF00949; Peptidase_S7; 1.
DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF101257; SSF101257; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1.
DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host autophagy by virus; ATP-binding;
KW Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; 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 Ion channel; Ion transport; Membrane; Metal-binding; Methyltransferase;
KW mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; Phosphoprotein; Protease; RNA-binding;
KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Secreted;
KW Serine protease; Suppressor of RNA silencing; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation; Viral attachment to host cell;
KW Viral envelope protein; Viral immunoevasion; Viral ion channel;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT CHAIN 1..3388
FT /note="Genome polyprotein"
FT /id="PRO_0000405217"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037969"
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_0000037970"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308286"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308287"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037971"
FT CHAIN 281..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037972"
FT CHAIN 776..1127
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037973"
FT CHAIN 1128..1345
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037974"
FT CHAIN 1346..1475
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037975"
FT CHAIN 1476..2090
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037976"
FT CHAIN 2091..2217
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037977"
FT PEPTIDE 2218..2240
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308289"
FT CHAIN 2241..2488
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037978"
FT CHAIN 2489..3388
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037979"
FT TOPO_DOM 1..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..725
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 747..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 753..773
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 774..1195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1196..1220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1221..1226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1227..1245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1246..1269
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1270..1290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1291
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1292..1310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1311..1317
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1318..1338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1339..1346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1347..1367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1368..1370
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1371..1391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1392..1447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1448..1468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1469..2144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2145..2165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2166..2167
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2168..2188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2189
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2190..2210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2211..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..2271
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2272..2292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2293..2313
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2314..2334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2335..2344
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2345..2365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2366..2410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2411..2431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2432..2456
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2457..2477
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2478..3388
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1476..1653
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1655..1811
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1821..1988
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2490..2752
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3017..3166
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 1398..1437
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1659..1662
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT MOTIF 1759..1762
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2565..2568
FT /note="SUMO-interacting motif"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT ACT_SITE 1526
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1550
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1610
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2549
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2634
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2669
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2705
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1668..1675
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2544
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 2575
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 2593
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 2620
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2635
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2707
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2926
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2930
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2935
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2938
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 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 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1127..1128
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1345..1346
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1475..1476
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1932
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1935
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2090..2091
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2217..2218
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2240..2241
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2488..2489
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2502
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2505
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2506
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2508
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2513
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2517
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2549
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2634
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2638
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2669
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2700
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2702
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2705
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2544
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 905
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 982
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1134
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2298
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2302
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2454
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 283..310
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 340..401
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 354..385
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 372..396
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 465..565
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 582..613
FT /evidence="ECO:0000269|PubMed:12759475"
FT DISULFID 779..790
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 830..918
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 954..998
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1055..1104
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1066..1088
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1087..1091
FT /evidence="ECO:0000269|PubMed:14981082"
FT CONFLICT 351
FT /note="D -> E (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 615
FT /note="T -> I (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="T -> I (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 670
FT /note="D -> N (in Ref. 5)"
FT /evidence="ECO:0000305"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1R6R"
FT HELIX 27..32
FT /evidence="ECO:0007829|PDB:1R6R"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1R6R"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:1R6R"
FT HELIX 63..69
FT /evidence="ECO:0007829|PDB:1R6R"
FT HELIX 75..95
FT /evidence="ECO:0007829|PDB:1R6R"
FT TURN 282..285
FT /evidence="ECO:0007829|PDB:1OKE"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 295..306
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 320..332
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 334..352
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 370..379
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 389..409
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 415..424
FT /evidence="ECO:0007829|PDB:1OK8"
FT TURN 428..432
FT /evidence="ECO:0007829|PDB:1OKE"
FT STRAND 440..444
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:1OK8"
FT TURN 456..458
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 459..467
FT /evidence="ECO:0007829|PDB:1OK8"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 490..495
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 500..502
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 523..526
FT /evidence="ECO:0007829|PDB:1OKE"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:1OK8"
FT HELIX 537..543
FT /evidence="ECO:0007829|PDB:1OK8"
FT TURN 544..546
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 552..559
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 562..571
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 586..594
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 600..606
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 608..610
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 617..624
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 631..633
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 645..649
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 653..661
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 667..673
FT /evidence="ECO:0007829|PDB:1OK8"
FT STRAND 1396..1402
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 1408..1413
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1414..1417
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 1427..1429
FT /evidence="ECO:0007829|PDB:4M9T"
FT STRAND 1495..1504
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1507..1517
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1520..1524
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 1525..1528
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1533..1535
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1538..1540
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1542..1546
FT /evidence="ECO:0007829|PDB:4M9K"
FT TURN 1547..1550
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1551..1557
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1570..1574
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1582..1586
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1589..1592
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1594..1601
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 1607..1609
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1613..1615
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1621..1625
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1628..1630
FT /evidence="ECO:0007829|PDB:4M9K"
FT STRAND 1636..1639
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 1641..1643
FT /evidence="ECO:0007829|PDB:4M9K"
FT HELIX 2497..2507
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2510..2517
FT /evidence="ECO:0007829|PDB:1L9K"
FT TURN 2518..2520
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2522..2525
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2527..2535
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2543..2545
FT /evidence="ECO:0007829|PDB:2P1D"
FT HELIX 2546..2554
FT /evidence="ECO:0007829|PDB:1L9K"
FT TURN 2555..2557
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2563..2568
FT /evidence="ECO:0007829|PDB:1L9K"
FT TURN 2571..2573
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2574..2579
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2585..2591
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2609..2611
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2612..2615
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2620..2622
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2629..2633
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2642..2657
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2665..2671
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2676..2688
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2692..2694
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2706..2709
FT /evidence="ECO:0007829|PDB:1L9K"
FT HELIX 2716..2729
FT /evidence="ECO:0007829|PDB:1L9K"
FT STRAND 2739..2742
FT /evidence="ECO:0007829|PDB:1L9K"
SQ SEQUENCE 3388 AA; 379219 MW; 79B7C87BE64D2D8F CRC64;
MNDQRKKARN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLFMAL VAFLRFLTIP
PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR TAGMIIMLIP TVMAFHLTTR
NGEPHMIVSR QEKGKSLLFK TKDGTNMCTL MAMDLGELCE DTITYKCPFL KQNEPEDIDC
WCNSTSTWVT YGTCTTTGEH RREKRSVALV PHVGMGLETR TETWMSSEGA WKHAQRIETW
ILRHPGFTIM AAILAYTIGT THFQRVLIFI LLTAIAPSMT MRCIGISNRD FVEGVSGGSW
VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP
TLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT CKKNMEGKIV QPENLEYTVV
ITPHSGEEHA VGNDTGKHGK EVKITPQSSI TEAELTGYGT VTMECSPRTG LDFNEMVLLQ
MKDKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM
HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI
VIRVQYEGDG SPCKTPFEIM DLEKRHVLGR LTTVNPIVTE KDSPVNIEAE PPFGDSYIII
GVEPGQLKLD WFKKGSSIGQ MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF
GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVSLV LVGIVTLYLG VMVQADSGCV
VSWKNKELKC GSGIFVTDNV HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN
LMWKQITSEL NHILSENEVK LTIMTGDIKG IMQVGKRSLR PQPTELRYSW KTWGKAKMLS
TELHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLRLREKQ DAFCDSKLMS
AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKSCHW PKSHTLWSNG VLESEMVIPK
NFAGPVSQHN NRPGYHTQTA GPWHLGKLEM DFDFCEGTTV VVTEDCGNRG PSLRTTTASG
KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VSSLVTAGHG QIDNFSLGIL
GMALFLEEML RTRVGTKHAI LLVAVSFVTL ITGNMSFRDL GRVMVMVGAT MTDDIGMGVT
YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLLSQ SSIPETILEL TDALALGMMV
LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKADWIP
LALTIKGLNP TAIFLTTLSR TSKKRSWPLN EAIMAVGMVS ILASSLLKND TPMTGPLVAG
GLLTVCYVLT GRSADLELER ATDVKWDDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL
TILIRTGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPVGK AELEDGAYRI
KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL
EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FRTNTGTIGA VSLDFSPGTS GSPIVDKKGK
VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP
AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF
TMRLLSPIRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF
PQSNAPIMDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KTGNDIAACL RKNGKRVIQL
SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG
PMPVTHSSAA QRRGRIGRNP RNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII
PSMFEPEREK VDAIDGEYRL RGEARKTFVD LMRRGDLPVW LAYKVAAEGI NYADRRWCFD
GTRNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFAAGRK SLTLNLITEM
GRLPTFMTQK ARDALDNLAV LHTAEAGGKA YNHALSELPE TLETLLLLTL LATVTGGIFL
FLMSGRGIGK MTLGMCCIIT ASILLWYAQI QPHWIAASII LEFFLIVLLI PEPEKQRTPQ
DNQLTYVIIA ILTVVAATMA NEMGFLEKTK KDLGLGNIAT QQPESNILDI DLRPASAWTL
YAVATTFITP MLRHSIENSS VNVSLTAIAN QATVLMGLGK GWPLSKMDIG VPLLAIGCYS
QVNPITLTAA LLLLVAHYAI IGPGLQAKAT REAQKRAAAG IMKNPTVDGI TVIDLDPIPY
DPKFEKQLGQ VMLLVLCVTQ VLMMRTTWAL CEALTLATGP VSTLWEGNPG RFWNTTIAVS
MANIFRGSYL AGAGLLFSIM KNTTSTRRGT GNIGETLGEK WKSRLNALGK SEFQIYKKSG
IQEVDRTLAK EGIKRGETDH HAVSRGSAKL RWFVERNLVT PEGKVVDLGC GRGGWSYYCG
GLKNVREVKG LTKGGPGHEE PIPMSTYGWN LVRLQSGVDV FFVPPEKCDT LLCDIGESSP
NPTVEAGRTL RVLNLVENWL NNNTQFCVKV LNPYMPSVIE RMETLQRKYG GALVRNPLSR
NSTHEMYWVS NASGNIVSSV NMISRMLINR FTMRHKKATY EPDVDLGSGT RNIGIESETP
NLDIIGKRIE KIKQEHETSW HYDQDHPYKT WAYHGSYETK QTGSASSMVN GVVRLLTKPW
DVVPMVTQMA MTDTTPFGQQ RVFKEKVDTR TQEPKEGTKK LMKITAEWLW KELGKKKTPR
MCTREEFTKK VRSNAALGAI FTDENKWKSA REAVEDSRFW ELVDKERNLH LEGKCETCVY
NMMGKREKKL GEFGKAKGSR AIWYMWLGAR FLEFEALGFL NEDHWFSREN SLSGVEGEGL
HKLGYILREV SKKEGGAMYA DDTAGWDTRI TIEDLKNEEM ITNHMAGEHK KLAEAIFKLT
YQNKVVRVQR PTPRGTVMDI ISRRDQRGSG QVGTYGLNTF TNMEAQLIRQ MEGEGIFKSI
QHLTASEEIA VQDWLARVGR ERLSRMAISG DDCVVKPLDD RFARALTALN DMGKVRKDIQ
QWEPSRGWND WTQVPFCSHH FHELIMKDGR TLVVPCRNQD ELIGRARISQ GAGWSLRETA
CLGKSYAQMW SLMYFHRRDL RLAANAICSA VPSHWVPTSR TTWSIHASHE WMTTEDMLTV
WNKVWILENP WMEDKTPVES WEEIPYLGKR EDQWCGSLIG LTSRATWAKN IQTAINQVRS
LIGNEEYTDY MPSMKRFRRE EEEAGVLW
