POLG_WNV
ID POLG_WNV Reviewed; 3430 AA.
AC P06935;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Peptide 2k;
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/Helicase 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=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=NS5;
OS West Nile virus (WNV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11082;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=8495; Alligator.
OH NCBI_TaxID=34610; Amblyomma variegatum (Tropical bont tick).
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=53527; Culex.
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=34627; Hyalomma marginatum.
OH NCBI_TaxID=308735; Mansonia uniformis.
OH NCBI_TaxID=308737; Mimomyia.
OH NCBI_TaxID=9940; Ovis aries (Sheep).
OH NCBI_TaxID=34630; Rhipicephalus.
OH NCBI_TaxID=34861; Sciurus niger (Eastern fox squirrel).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3753811; DOI=10.1016/0042-6822(86)90082-6;
RA Castle E., Leidner U., Nowak T., Wengler G., Wengler G.;
RT "Primary structure of the West Nile flavivirus genome region coding for all
RT nonstructural proteins.";
RL Virology 149:10-26(1986).
RN [2]
RP SEQUENCE REVISION TO 1908; 2018-2036; 2242 AND 2859-2860.
RX PubMed=11277701; DOI=10.1006/viro.2000.0795;
RA Yamshchikov V.F., Wengler G., Perelygin A.A., Brinton M.A., Compans R.W.;
RT "An infectious clone of the West Nile flavivirus.";
RL Virology 281:294-304(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-291.
RX PubMed=2992152; DOI=10.1016/0042-6822(85)90156-4;
RA Castle E., Nowak T., Leidner U., Wengler G., Wengler G.;
RT "Sequence analysis of the viral core protein and the membrane-associated
RT proteins V1 and NV2 of the flavivirus West Nile virus and of the genome
RT sequence for these proteins.";
RL Virology 145:227-236(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 255-854.
RX PubMed=3855247; DOI=10.1016/0042-6822(85)90129-1;
RA Wengler G., Castle E., Leidner U., Nowak T., Wengler G.;
RT "Sequence analysis of the membrane protein V3 of the flavivirus West Nile
RT virus and of its gene.";
RL Virology 147:264-274(1985).
RN [5]
RP ABSENCE OF GLYCOSYLATION (ENVELOPE PROTEIN E).
RX PubMed=2441520; DOI=10.1016/0042-6822(87)90460-0;
RA Winkler G., Heinz F.X., Kunz C.;
RT "Studies on the glycosylation of flavivirus E proteins and the role of
RT carbohydrate in antigenic structure.";
RL Virology 159:237-243(1987).
RN [6]
RP DISULFIDE BONDS (ENVELOPE PROTEIN E).
RX PubMed=3811228; DOI=10.1016/0042-6822(87)90443-0;
RA Nowak T., Wengler G.;
RT "Analysis of disulfides present in the membrane proteins of the West Nile
RT flavivirus.";
RL Virology 156:127-137(1987).
RN [7]
RP FUNCTION (ENVELOPE PROTEIN E).
RX PubMed=15367621; DOI=10.1128/jvi.78.19.10543-10555.2004;
RA Chu J.J., Ng M.L.;
RT "Infectious entry of West Nile virus occurs through a clathrin-mediated
RT endocytic pathway.";
RL J. Virol. 78:10543-10555(2004).
RN [8]
RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5).
RC STRAIN=E101;
RX PubMed=16699025; DOI=10.1128/jvi.01982-05;
RA Uchil P.D., Kumar A.V., Satchidanandam V.;
RT "Nuclear localization of flavivirus RNA synthesis in infected cells.";
RL J. Virol. 80:5451-5464(2006).
RN [9]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF LYS-2586;
RP ASP-2671; LYS-2707 AND GLU-2743.
RX PubMed=17267492; DOI=10.1128/jvi.02704-06;
RA Zhou Y., Ray D., Zhao Y., Dong H., Ren S., Li Z., Guo Y., Bernard K.A.,
RA Shi P.-Y., Li H.;
RT "Structure and function of flavivirus NS5 methyltransferase.";
RL J. Virol. 81:3891-3903(2007).
RN [10]
RP PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX PubMed=17067286; DOI=10.1042/bj20061136;
RA Shiryaev S.A., Kozlov I.A., Ratnikov B.I., Smith J.W., Lebl M.,
RA Strongin A.Y.;
RT "Cleavage preference distinguishes the two-component NS2B-NS3 serine
RT proteinases of Dengue and West Nile viruses.";
RL Biochem. J. 401:743-752(2007).
RN [11]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), AND SUBCELLULAR LOCATION
RP (CAPSID PROTEIN C).
RX PubMed=19889084; DOI=10.1111/j.1462-5822.2009.01407.x;
RA Bhuvanakantham R., Li J., Tan T.T., Ng M.L.;
RT "Human Sec3 protein is a novel transcriptional and translational repressor
RT of flavivirus.";
RL Cell. Microbiol. 12:453-472(2010).
RN [12]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), FUNCTION (CAPSID PROTEIN
RP C), AND MUTAGENESIS OF VAL-14.
RX PubMed=23522008; DOI=10.1111/cmi.12143;
RA Bhuvanakantham R., Ng M.L.;
RT "West Nile virus and dengue virus capsid protein negates the antiviral
RT activity of human Sec3 protein through the proteasome pathway.";
RL Cell. Microbiol. 15:1688-1706(2013).
RN [13]
RP INTERACTION WITH HUMAN PAF1 COMPLEX (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028;
RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L.,
RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B.,
RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M.,
RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S.,
RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A.,
RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J.,
RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.;
RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms
RT of Dengue and Zika Virus Pathogenesis.";
RL Cell 175:1931-1945(2018).
RN [14]
RP DOMAIN (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=33547379; DOI=10.1038/s41598-021-82751-x;
RA Giraud E., Del Val C.O., Caillet-Saguy C., Zehrouni N., Khou C.,
RA Caillet J., Jacob Y., Pardigon N., Wolff N.;
RT "Role of PDZ-binding motif from West Nile virus NS5 protein on viral
RT replication.";
RL Sci. Rep. 11:3266-3266(2021).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 1420-1688.
RX PubMed=16532006; DOI=10.1038/nsmb1073;
RA Erbel P., Schiering N., D'Arcy A., Renatus M., Kroemer M., Lim S.P.,
RA Yin Z., Keller T.H., Vasudevan S.G., Hommel U.;
RT "Structural basis for the activation of flaviviral NS3 proteases from
RT dengue and West Nile virus.";
RL Nat. Struct. Mol. Biol. 13:372-373(2006).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1419-1679.
RX PubMed=17400917; DOI=10.1110/ps.072753207;
RA Aleshin A.E., Shiryaev S.A., Strongin A.Y., Liddington R.C.;
RT "Structural evidence for regulation and specificity of flaviviral proteases
RT and evolution of the Flaviviridae fold.";
RL Protein Sci. 16:795-806(2007).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 291-688.
RX PubMed=19713934; DOI=10.1038/emboj.2009.245;
RA Cherrier M.V., Kaufmann B., Nybakken G.E., Lok S.M., Warren J.T.,
RA Chen B.R., Nelson C.A., Kostyuchenko V.A., Holdaway H.A., Chipman P.R.,
RA Kuhn R.J., Diamond M.S., Rossmann M.G., Fremont D.H.;
RT "Structural basis for the preferential recognition of immature flaviviruses
RT by a fusion-loop antibody.";
RL EMBO J. 28:3269-3276(2009).
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 (By similarity). During
CC virus entry, may induce genome penetration into the host cytoplasm
CC after hemifusion induced by the surface proteins (By similarity). Can
CC migrate to the cell nucleus where it modulates host functions (By
CC similarity). Overcomes the anti-viral effects of host EXOC1 by
CC sequestering and degrading the latter through the proteasome
CC degradation pathway (PubMed:23522008). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:23522008}.
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 (PubMed:15367621).
CC Envelope protein is synthesized in the endoplasmic reticulum in the
CC form of heterodimer with protein prM (By similarity). They play a role
CC in virion budding in the ER, and the newly formed immature particle is
CC covered with 60 spikes composed of heterodimer between precursor prM
CC and envelope protein E (By similarity). The virion is transported to
CC the Golgi apparatus where the low pH causes dissociation of PrM-E
CC heterodimers and formation of E homodimers (By similarity). prM-E
CC cleavage is inefficient, and many virions are only partially matured
CC (By similarity). These uncleaved prM would play a role in immune
CC evasion (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host alpha/beta interferon antiviral response.
CC {ECO:0000250|UniProtKB:P14335}.
CC -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the
CC serine protease function of NS3. May have membrane-destabilizing
CC activity and form viroporins (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.
CC -!- FUNCTION: [Serine protease/Helicase NS3]: Displays three enzymatic
CC activities: serine protease, NTPase and RNA helicase. NS3 serine
CC protease, in association with NS2B, performs its autocleavage and
CC cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-
CC NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds
CC RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). NS3
CC supports the separation of RNA daughter and template strands during
CC viral replication. The helicase part is involved in the inhibition of
CC phosphorylation of host STAT1, and thereby inhibition of host type-I
CC IFN signaling (By similarity). In addition, NS3 assists the initiation
CC of replication by unwinding the RNA secondary structure in the 3' non-
CC translated region (NTR). Inhibits STAT2 translocation in the nucleus
CC after IFN-alpha treatment (By similarity).
CC {ECO:0000250|UniProtKB:P14335, ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000255|PROSITE-ProRule:PRU00860}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC required for the interferon antagonism activity of the latter.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-
CC derived membrane vesicles where the viral replication takes place.
CC Inhibits interferon (IFN)-induced host STAT1 phosphorylation and
CC nuclear translocation, thereby preventing the establishment of cellular
CC antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2
CC translocation in the nucleus after IFN-alpha treatment.
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm (PubMed:17267492). NS5 methylates viral RNA cap at guanine N-
CC 7 and ribose 2'-O positions (PubMed:17267492). Besides its role in RNA
CC genome replication, also prevents the establishment of cellular
CC antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta)
CC signaling pathway (By similarity). Inhibits host TYK2 and STAT2
CC phosphorylation, thereby preventing activation of JAK-STAT signaling
CC pathway (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:17267492}.
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 Evidence={ECO:0000250|UniProtKB:Q9Q6P4};
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 (By similarity). Interacts (via
CC N-terminus) with host EXOC1 (via C-terminus) (PubMed:19889084,
CC PubMed:23522008); this interaction results in EXOC1 degradation through
CC the proteasome degradation pathway (PubMed:23522008).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:19889084,
CC ECO:0000269|PubMed:23522008}.
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). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (By similarity). Interacts with envelope protein E (By
CC similarity). NS1 interacts with NS4B (By similarity). Interacts with
CC host complement protein CFH; this interaction leads to the degradation
CC of C3 (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3 (By similarity). May form homooligomers (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease/Helicase NS3]: Forms a heterodimer with NS2B
CC (By similarity). Interacts with NS4B (By similarity). Interacts with
CC unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with Serine
CC protease/Helicase NS3 (By similarity). Interacts with NS1 (By
CC similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q9Q6P4}.
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 host PAF1 complex (PubMed:30550790).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:30550790}.
CC -!- INTERACTION:
CC P06935; P05106: ITGB3; Xeno; NbExp=4; IntAct=EBI-981051, EBI-702847;
CC PRO_0000037746; Q17NZ6: CTLMA15; Xeno; NbExp=5; IntAct=EBI-2912469, EBI-2912457;
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC {ECO:0000269|PubMed:19889084}. Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:19889084}.
CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane;
CC Peripheral membrane protein; Lumenal side
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC reticulum membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease/Helicase NS3]: Host endoplasmic
CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral
CC membrane protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic
CC side {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-
CC covalently associated to serine protease subunit NS2B.
CC {ECO:0000255|PROSITE-ProRule:PRU00860}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P14335}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated
CC vesicles hosting the replication complex.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex.
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase NS5]: Host
CC endoplasmic reticulum membrane; Peripheral membrane protein;
CC Cytoplasmic side. Host nucleus {ECO:0000269|PubMed:16699025}. Host
CC cytoplasm {ECO:0000250|UniProtKB:P14335}. Note=Located in RE-associated
CC vesicles hosting the replication complex. NS5 protein is mainly
CC localized in the nucleus rather than in ER vesicles (By similarity).
CC Shuttles between the cytoplasm and nucleus (By similarity).
CC {ECO:0000250|UniProtKB:P14335, ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Small envelope protein M]: The transmembrane domains contain
CC an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Envelope protein E]: The transmembrane domains contain an
CC endoplasmic reticulum retention signal. {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [RNA-directed RNA polymerase NS5]: Contains a PDZ-binding motif
CC that binds to several PDZ-containing cellular proteins. These
CC interactions seem necessary for an optimal viral replication.
CC {ECO:0000269|PubMed:33547379}.
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 ECO:0000269|PubMed:17067286}.
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]: Not N-glycosylated.
CC {ECO:0000269|PubMed:2441520}.
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]: 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}.
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DR EMBL; M12294; AAA48498.2; -; Genomic_RNA.
DR PIR; A25256; GNWVWV.
DR RefSeq; NP_041724.2; NC_001563.2.
DR PDB; 2FP7; X-ray; 1.68 A; A=1420-1466, B=1517-1688.
DR PDB; 2GGV; X-ray; 1.80 A; A=1419-1525, B=1503-1679.
DR PDB; 2IJO; X-ray; 2.30 A; A=1419-1482, B=1502-1685.
DR PDB; 2P5P; X-ray; 2.80 A; A/B/C=585-701.
DR PDB; 2YOL; X-ray; 3.20 A; A=1420-1465, A=1502-1671.
DR PDB; 3E90; X-ray; 2.45 A; A/C=1420-1463, B/D=1502-1685.
DR PDB; 3I50; X-ray; 3.00 A; E=291-688.
DR PDB; 5IDK; X-ray; 1.50 A; A/B/C=1420-1465.
DR PDBsum; 2FP7; -.
DR PDBsum; 2GGV; -.
DR PDBsum; 2IJO; -.
DR PDBsum; 2P5P; -.
DR PDBsum; 2YOL; -.
DR PDBsum; 3E90; -.
DR PDBsum; 3I50; -.
DR PDBsum; 5IDK; -.
DR BMRB; P06935; -.
DR SMR; P06935; -.
DR IntAct; P06935; 4.
DR BindingDB; P06935; -.
DR ChEMBL; CHEMBL5419; -.
DR MEROPS; S07.003; -.
DR PRIDE; P06935; -.
DR ABCD; P06935; 11 sequenced antibodies.
DR GeneID; 912267; -.
DR KEGG; vg:912267; -.
DR BRENDA; 2.7.7.48; 6687.
DR BRENDA; 3.4.21.91; 6687.
DR EvolutionaryTrace; P06935; -.
DR PRO; PR:P06935; -.
DR Proteomes; UP000008600; Genome.
DR GO; GO:0039714; C:cytoplasmic viral factory; IDA:UniProtKB.
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: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:0032993; C:protein-DNA complex; IMP:CAFA.
DR GO; GO:1990904; C:ribonucleoprotein complex; IMP:CAFA.
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:0003677; F:DNA binding; IMP:CAFA.
DR GO; GO:1990814; F:DNA/DNA annealing activity; IMP:CAFA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0140272; F:exogenous protein binding; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:CACAO.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IMP:CAFA.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0033592; F:RNA strand annealing activity; IMP:CAFA.
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; IDA:UniProtKB.
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:0045070; P:positive regulation of viral genome replication; IMP:CACAO.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0106005; P:RNA 5'-cap (guanine-N7)-methylation; IDA:UniProtKB.
DR GO; GO:0043489; P:RNA stabilization; IMP:CAFA.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IDA:CACAO.
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:0039576; P:suppression by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 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: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; DP00673; -.
DR Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 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; 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; Host nucleus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host JAK1 by virus; Inhibition of host STAT1 by virus;
KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus;
KW Membrane; 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;
KW Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT CHAIN 1..3430
FT /note="Genome polyprotein"
FT /id="PRO_0000441418"
FT CHAIN 1..105
FT /note="Capsid protein C"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037743"
FT PROPEP 106..123
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037744"
FT CHAIN 124..290
FT /note="Protein prM"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000405150"
FT CHAIN 124..215
FT /note="Peptide pr"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000405151"
FT CHAIN 216..290
FT /note="Small envelope protein M"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037745"
FT CHAIN 291..787
FT /note="Envelope protein E"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037746"
FT CHAIN 788..1139
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037747"
FT CHAIN 1140..1370
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037748"
FT CHAIN 1371..1501
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037749"
FT CHAIN 1502..2120
FT /note="Serine protease/Helicase NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037750"
FT CHAIN 2121..2246
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037751"
FT PEPTIDE 2247..2269
FT /note="Peptide 2k"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000405152"
FT CHAIN 2270..2525
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037752"
FT CHAIN 2526..3430
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037753"
FT TOPO_DOM 2..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..290
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 291..739
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..760
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 761..766
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 767..787
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 788..1212
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1213..1233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1234..1243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1244..1264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1265..1278
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1279..1299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1300..1307
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1308..1328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1329..1340
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1341..1361
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1362..1371
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1372..1392
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1393..1395
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1396..1416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1417..1473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1474..1494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1495..2170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2171..2191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2192..2196
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2197..2217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2218
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2219..2239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2240..2254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2255..2275
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2276..2309
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2310..2330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2331..2377
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2378..2398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2399..2441
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2442..2462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2463..2467
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2468..2488
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2489..3430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1502..1679
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1682..1838
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1849..2014
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2526..2791
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3055..3207
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 2..15
FT /note="Interaction with host EXOC1"
FT /evidence="ECO:0000269|PubMed:19889084"
FT REGION 37..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 388..401
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1424..1463
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1686..1689
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT REGION 2165..2169
FT /note="Regulates the ATPase activity of NS3 helicase"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT MOTIF 1786..1789
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2914..2916
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT MOTIF 3428..3430
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:33547379"
FT ACT_SITE 1552
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1576
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1636
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2586
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2671
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2707
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2743
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1695..1702
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2581
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2611
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2612
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2629
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2630
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2656
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2657
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2672
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2745
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2965
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2969
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2974
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2977
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3258
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 105..106
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 123..124
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 215..216
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 290..291
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 787..788
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 1139..1140
FT /note="Cleavage; by host"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 1370..1371
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1501..1502
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1959
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1962
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2120..2121
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 2246..2247
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 2269..2270
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000303|PubMed:17067286"
FT SITE 2525..2526
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 2538
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2541
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2542
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2544
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2549
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:17067286"
FT SITE 2553
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2586
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2671
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2675
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2707
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2738
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2740
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2743
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2581
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT CARBOHYD 917
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 962
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 994
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 293..320
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 350..411
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 350..406
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 364..395
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 382..411
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 382..406
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 476..574
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 591..622
FT /evidence="ECO:0000269|PubMed:3811228"
FT DISULFID 791..802
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 842..930
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 966..1010
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1067..1116
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1078..1099
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1100..1103
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT MUTAGEN 14
FT /note="V->A: Loss of interaction between capsid protein C
FT and host EXOC1."
FT /evidence="ECO:0000269|PubMed:23522008"
FT MUTAGEN 2586
FT /note="K->A: Complete loss of 2'-O-methyltransferase
FT activity. No effect on N-7 methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2671
FT /note="D->A: Lethal for the virus. Complete loss of 2'-O
FT and N-7 methyltransferase activities."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2707
FT /note="K->A: Complete loss of 2'-O-methyltransferase
FT activity. No effect on N-7 methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2743
FT /note="E->A: Complete loss of 2'-O-methyltransferase
FT activity. No effect on N-7 methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT STRAND 595..603
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 605..607
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 609..615
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 626..631
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 634..637
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 639..643
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 657..662
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 665..673
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 679..685
FT /evidence="ECO:0007829|PDB:2P5P"
FT STRAND 1422..1428
FT /evidence="ECO:0007829|PDB:5IDK"
FT HELIX 1434..1439
FT /evidence="ECO:0007829|PDB:2GGV"
FT STRAND 1440..1443
FT /evidence="ECO:0007829|PDB:2GGV"
FT STRAND 1444..1449
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1451..1453
FT /evidence="ECO:0007829|PDB:2YOL"
FT STRAND 1455..1457
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1503..1505
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1521..1532
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1534..1543
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1546..1549
FT /evidence="ECO:0007829|PDB:5IDK"
FT HELIX 1551..1554
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1559..1561
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1564..1566
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1568..1572
FT /evidence="ECO:0007829|PDB:5IDK"
FT TURN 1573..1576
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1577..1583
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1592..1594
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1596..1600
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1608..1612
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1615..1618
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1623..1627
FT /evidence="ECO:0007829|PDB:5IDK"
FT HELIX 1633..1635
FT /evidence="ECO:0007829|PDB:2FP7"
FT STRAND 1639..1641
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1647..1650
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1654..1656
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1662..1665
FT /evidence="ECO:0007829|PDB:5IDK"
FT STRAND 1672..1674
FT /evidence="ECO:0007829|PDB:2IJO"
SQ SEQUENCE 3430 AA; 380110 MW; 42D71B7CB12DC45B CRC64;
MSKKPGGPGK NRAVNMLKRG MPRGLSLIGL KRAMLSLIDG KGPIRFVLAL LAFFRFTAIA
PTRAVLDRWR GVNKQTAMKH LLSFKKELGT LTSAINRRST KQKKRGGTAG FTILLGLIAC
AGAVTLSNFQ GKVMMTVNAT DVTDVITIPT AAGKNLCIVR AMDVGYLCED TITYECPVLA
AGNDPEDIDC WCTKSSVYVR YGRCTKTRHS RRSRRSLTVQ THGESTLANK KGAWLDSTKA
TRYLVKTESW ILRNPGYALV AAVIGWMLGS NTMQRVVFAI LLLLVAPAYS FNCLGMSNRD
FLEGVSGATW VDLVLEGDSC VTIMSKDKPT IDVKMMNMEA ANLADVRSYC YLASVSDLST
RAACPTMGEA HNEKRADPAF VCKQGVVDRG WGNGCGLFGK GSIDTCAKFA CTTKATGWII
QKENIKYEVA IFVHGPTTVE SHGKIGATQA GRFSITPSAP SYTLKLGEYG EVTVDCEPRS
GIDTSAYYVM SVGEKSFLVH REWFMDLNLP WSSAGSTTWR NRETLMEFEE PHATKQSVVA
LGSQEGALHQ ALAGAIPVEF SSNTVKLTSG HLKCRVKMEK LQLKGTTYGV CSKAFKFART
PADTGHGTVV LELQYTGTDG PCKVPISSVA SLNDLTPVGR LVTVNPFVSV ATANSKVLIE
LEPPFGDSYI VVGRGEQQIN HHWHKSGSSI GKAFTTTLRG AQRLAALGDT AWDFGSVGGV
FTSVGKAIHQ VFGGAFRSLF GGMSWITQGL LGALLLWMGI NARDRSIAMT FLAVGGVLLF
LSVNVHADTG CAIDIGRQEL RCGSGVFIHN DVEAWMDRYK FYPETPQGLA KIIQKAHAEG
VCGLRSVSRL EHQMWEAIKD ELNTLLKENG VDLSVVVEKQ NGMYKAAPKR LAATTEKLEM
GWKAWGKSII FAPELANNTF VIDGPETEEC PTANRAWNSM EVEDFGFGLT STRMFLRIRE
TNTTECDSKI IGTAVKNNMA VHSDLSYWIE SGLNDTWKLE RAVLGEVKSC TWPETHTLWG
DGVLESDLII PITLAGPRSN HNRRPGYKTQ NQGPWDEGRV EIDFDYCPGT TVTISDSCEH
RGPAARTTTE SGKLITDWCC RSCTLPPLRF QTENGCWYGM EIRPTRHDEK TLVQSRVNAY
NADMIDPFQL GLMVVFLATQ EVLRKRWTAK ISIPAIMLAL LVLVFGGITY TDVLRYVILV
GAAFAEANSG GDVVHLALMA TFKIQPVFLV ASFLKARWTN QESILLMLAA AFFQMAYYDA
KNVLSWEVPD VLNSLSVAWM ILRAISFTNT SNVVVPLLAL LTPGLKCLNL DVYRILLLMV
GVGSLIKEKR SSAAKKKGAC LICLALASTG VFNPMILAAG LMACDPNRKR GWPATEVMTA
VGLMFAIVGG LAELDIDSMA IPMTIAGLMF AAFVISGKST DMWIERTADI TWESDAEITG
SSERVDVRLD DDGNFQLMND PGAPWKIWML RMACLAISAY TPWAILPSVI GFWITLQYTK
RGGVLWDTPS PKEYKKGDTT TGVYRIMTRG LLGSYQAGAG VMVEGVFHTL WHTTKGAALM
SGEGRLDPYW GSVKEDRLCY GGPWKLQHKW NGHDEVQMIV VEPGKNVKNV QTKPGVFKTP
EGEIGAVTLD YPTGTSGSPI VDKNGDVIGL YGNGVIMPNG SYISAIVQGE RMEEPAPAGF
EPEMLRKKQI TVLDLHPGAG KTRKILPQII KEAINKRLRT AVLAPTRVVA AEMSEALRGL
PIRYQTSAVH REHSGNEIVD VMCHATLTHR LMSPHRVPNY NLFIMDEAHF TDPASIAARG
YIATKVELGE AAAIFMTATP PGTSDPFPES NAPISDMQTE IPDRAWNTGY EWITEYVGKT
VWFVPSVKMG NEIALCLQRA GKKVIQLNRK SYETEYPKCK NDDWDFVITT DISEMGANFK
ASRVIDSRKS VKPTIIEEGD GRVILGEPSA ITAASAAQRR GRIGRNPSQV GDEYCYGGHT
NEDDSNFAHW TEARIMLDNI NMPNGLVAQL YQPEREKVYT MDGEYRLRGE ERKNFLEFLR
TADLPVWLAY KVAAAGISYH DRKWCFDGPR TNTILEDNNE VEVITKLGER KILRPRWADA
RVYSDHQALK SFKDFASGKR SQIGLVEVLG RMPEHFMVKT WEALDTMYVV ATAEKGGRAH
RMALEELPDA LQTIVLIALL SVMSLGVFFL LMQRKGIGKI GLGGVILGAA TFFCWMAEVP
GTKIAGMLLL SLLLMIVLIP EPEKQRSQTD NQLAVFLICV LTLVGAVAAN EMGWLDKTKN
DIGSLLGHRP EARETTLGVE SFLLDLRPAT AWSLYAVTTA VLTPLLKHLI TSDYINTSLT
SINVQASALF TLARGFPFVD VGVSALLLAV GCWGQVTLTV TVTAAALLFC HYAYMVPGWQ
AEAMRSAQRR TAAGIMKNVV VDGIVATDVP ELERTTPVMQ KKVGQIILIL VSMAAVVVNP
SVRTVREAGI LTTAAAVTLW ENGASSVWNA TTAIGLCHIM RGGWLSCLSI MWTLIKNMEK
PGLKRGGAKG RTLGEVWKER LNHMTKEEFT RYRKEAITEV DRSAAKHARR EGNITGGHPV
SRGTAKLRWL VERRFLEPVG KVVDLGCGRG GWCYYMATQK RVQEVKGYTK GGPGHEEPQL
VQSYGWNIVT MKSGVDVFYR PSEASDTLLC DIGESSSSAE VEEHRTVRVL EMVEDWLHRG
PKEFCIKVLC PYMPKVIEKM ETLQRRYGGG LIRNPLSRNS THEMYWVSHA SGNIVHSVNM
TSQVLLGRME KKTWKGPQFE EDVNLGSGTR AVGKPLLNSD TSKIKNRIER LKKEYSSTWH
QDANHPYRTW NYHGSYEVKP TGSASSLVNG VVRLLSKPWD TITNVTTMAM TDTTPFGQQR
VFKEKVDTKA PEPPEGVKYV LNETTNWLWA FLARDKKPRM CSREEFIGKV NSNAALGAMF
EEQNQWKNAR EAVEDPKFWE MVDEEREAHL RGECNTCIYN MMGKREKKPG EFGKAKGSRA
IWFMWLGARF LEFEALGFLN EDHWLGRKNS GGGVEGLGLQ KLGYILKEVG TKPGGKVYAD
DTAGWDTRIT KADLENEAKV LELLDGEHRR LARSIIELTY RHKVVKVMRP AADGKTVMDV
ISREDQRGSG QVVTYALNTF TNLAVQLVRM MEGEGVIGPD DVEKLGKGKG PKVRTWLFEN
GEERLSRMAV SGDDCVVKPL DDRFATSLHF LNAMSKVRKD IQEWKPSTGW YDWQQVPFCS
NHFTELIMKD GRTLVVPCRG QDELIGRARI SPGAGWNVRD TACLAKSYAQ MWLLLYFHRR
DLRLMANAIC SAVPANWVPT GRTTWSIHAK GEWMTTEDML AVWNRVWIEE NEWMEDKTPV
ERWSDVPYSG KREDIWCGSL IGTRTRATWA ENIHVAINQV RSVIGEEKYV DYMSSLRRYE
DTIVVEDTVL
