POLG_WNV9
ID POLG_WNV9 Reviewed; 3433 AA.
AC Q9Q6P4;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 2.
DT 03-AUG-2022, entry version 189.
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:0000269|PubMed:19474250};
DE EC=3.6.4.13 {ECO:0000269|PubMed:19474250};
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, ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:20685660};
DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924, ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:20685660};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=NS5;
GN Name=GP1 {ECO:0000312|EMBL:ANW69091.1};
GN ORFNames=MZ11_60484gpGP1 {ECO:0000312|EMBL:ANW69091.1},
GN MZ11_60553gpGP1 {ECO:0000312|EMBL:ANW69112.1};
OS West Nile virus (strain NY-99) (WNV) (West Nile virus (strain NY-1999)).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=1968826;
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=34630; Rhipicephalus.
OH NCBI_TaxID=34861; Sciurus niger (Eastern fox squirrel).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=Isolate US/NY99-flamingo382/1999;
RX PubMed=10600742; DOI=10.1126/science.286.5448.2333;
RA Lanciotti R.S., Roehrig J.T., Deubel V., Smith J., Parker M., Steele K.,
RA Crise B., Volpe K.E., Crabtree M.B., Scherret J.H., Hall R.A.,
RA MacKenzie J.S., Cropp C.B., Panigrahy B., Ostlund E., Schmitt B.,
RA Malkinson M., Banet C., Weissman J., Komar N., Savage H.M., Stone W.,
RA McNamara T., Gubler D.J.;
RT "Origin of the West Nile virus responsible for an outbreak of encephalitis
RT in the northeastern United States.";
RL Science 286:2333-2337(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=Isolate US/NY2000-grouse3282/2000;
RX PubMed=12093177; DOI=10.1006/viro.2002.1449;
RA Lanciotti R.S., Ebel G.D., Deubel V., Kerst A.J., Murri S., Meyer R.,
RA Bowen M., McKinney N., Morrill W.E., Crabtree M.B., Kramer L.D.,
RA Roehrig J.T.;
RT "Complete genome sequences and phylogenetic analysis of West Nile virus
RT strains isolated from the United States, Europe, and the Middle East.";
RL Virology 298:96-105(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=Isolate US/NY99-6922/1999;
RX PubMed=15557236; DOI=10.1099/vir.0.80247-0;
RA Shirato K., Miyoshi H., Goto A., Ako Y., Ueki T., Kariwa H., Takashima I.;
RT "Viral envelope protein glycosylation is a molecular determinant of the
RT neuroinvasiveness of the New York strain of West Nile virus.";
RL J. Gen. Virol. 85:3637-3645(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=NV-1/US/BID-V4187/1999, US/BID-V4186/1999, US/BID-V4188/1999, and
RC US/BID-V4189/1999;
RX PubMed=21723580; DOI=10.1016/j.virol.2011.06.006;
RA Armstrong P.M., Vossbrinck C.R., Andreadis T.G., Anderson J.F., Pesko K.N.,
RA Newman R.M., Lennon N.J., Birren B.W., Ebel G.D., Henn M.R.;
RT "Molecular evolution of West Nile virus in a northern temperate region:
RT Connecticut, USA 1999-2008.";
RL Virology 417:203-210(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RA Gao Y.W., Fan S.T., Sun H.T., Wang Z., Gao X.L., Li Y.G., Wang T.C.,
RA Zhang K., Xu W.W., Yu Z.J., Xia X.Z.;
RL Submitted (DEC-2012) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=US/NY99-P2/1999;
RA Grinev A., Anez G., Rios M.;
RT "Complete genome sequence of West Nile virus strains used for the
RT formulation of CBER/FDA RNA reference reagents and lot release panels for
RT nucleic acid testing.";
RL Genome Announc. 2:E00811-E00814(2014).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=Culex/USA/29000529/2000, and Culex/USA/33020090/2002;
RA Florea S., Webb J.S., Jaromczyk J., Schardl C.L.;
RL Submitted (JUL-2016) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4B).
RX PubMed=15956546; DOI=10.1128/jvi.79.13.8004-8013.2005;
RA Munoz-Jordan J.L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L.,
RA Ashok M., Lipkin W.I., Garcia-Sastre A.;
RT "Inhibition of alpha/beta interferon signaling by the NS4B protein of
RT flaviviruses.";
RL J. Virol. 79:8004-8013(2005).
RN [9]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=15650160; DOI=10.1128/jvi.79.3.1343-1350.2005;
RA Guo J.T., Hayashi J., Seeger C.;
RT "West Nile virus inhibits the signal transduction pathway of alpha
RT interferon.";
RL J. Virol. 79:1343-1350(2005).
RN [10]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1), AND INTERACTION WITH HOST COMPLEMENT
RP REGULATORY PROTEIN FACTOR H (NON-STRUCTURAL PROTEIN 1).
RX PubMed=17132743; DOI=10.1073/pnas.0605668103;
RA Chung K.M., Liszewski M.K., Nybakken G., Davis A.E., Townsend R.R.,
RA Fremont D.H., Atkinson J.P., Diamond M.S.;
RT "West Nile virus nonstructural protein NS1 inhibits complement activation
RT by binding the regulatory protein factor H.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:19111-19116(2006).
RN [11]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A), CATALYTIC ACTIVITY (SERINE
RP PROTEASE/HELICASE NS3), AND MUTAGENESIS OF 2169-GLU--ASP-2173.
RX PubMed=19474250; DOI=10.1099/vir.0.012864-0;
RA Shiryaev S.A., Chernov A.V., Aleshin A.E., Shiryaeva T.N., Strongin A.Y.;
RT "NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor
RT role of the non-structural protein NS4A from West Nile virus.";
RL J. Gen. Virol. 90:2081-2085(2009).
RN [12]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF LYS-2557.
RX PubMed=19850911; DOI=10.1261/rna.1609709;
RA Issur M., Geiss B.J., Bougie I., Picard-Jean F., Despins S., Mayette J.,
RA Hobdey S.E., Bisaillon M.;
RT "The flavivirus NS5 protein is a true RNA guanylyltransferase that
RT catalyzes a two-step reaction to form the RNA cap structure.";
RL RNA 15:2340-2350(2009).
RN [13]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=20106931; DOI=10.1128/jvi.01161-09;
RA Laurent-Rolle M., Boer E.F., Lubick K.J., Wolfinbarger J.B., Carmody A.B.,
RA Rockx B., Liu W., Ashour J., Shupert W.L., Holbrook M.R., Barrett A.D.,
RA Mason P.W., Bloom M.E., Garcia-Sastre A., Khromykh A.A., Best S.M.;
RT "The NS5 protein of the virulent West Nile virus NY99 strain is a potent
RT antagonist of type I interferon-mediated JAK-STAT signaling.";
RL J. Virol. 84:3503-3515(2010).
RN [14]
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 4B (NON-STRUCTURAL PROTEIN 1), AND
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 1 (NON-STRUCTURAL PROTEIN 4B).
RX PubMed=22553322; DOI=10.1128/jvi.00157-12;
RA Youn S., Li T., McCune B.T., Edeling M.A., Fremont D.H., Cristea I.M.,
RA Diamond M.S.;
RT "Evidence for a genetic and physical interaction between nonstructural
RT proteins NS1 and NS4B that modulates replication of West Nile virus.";
RL J. Virol. 86:7360-7371(2012).
RN [15]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=24245822; DOI=10.1186/1743-422x-10-339;
RA Youn S., Ambrose R.L., Mackenzie J.M., Diamond M.S.;
RT "Non-structural protein-1 is required for West Nile virus replication
RT complex formation and viral RNA synthesis.";
RL Virol. J. 10:339-339(2013).
RN [16]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4B), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP PROTEIN 4B), SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 1), SUBCELLULAR
RP LOCATION (NON-STRUCTURAL PROTEIN 4A), AND FUNCTION (NON-STRUCTURAL PROTEIN
RP 1).
RX PubMed=24465392; DOI=10.1371/journal.pone.0084040;
RA Kaufusi P.H., Kelley J.F., Yanagihara R., Nerurkar V.R.;
RT "Induction of endoplasmic reticulum-derived replication-competent membrane
RT structures by West Nile virus non-structural protein 4B.";
RL PLoS ONE 9:E84040-E84040(2014).
RN [17]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1), AND MUTAGENESIS OF THR-968; ASN-982;
RP GLU-1029; ASN-1046; GLY-1086; THR-1108; PRO-1111 AND MET-1124.
RX PubMed=24889229; DOI=10.1016/j.virol.2014.03.017;
RA Morrison C.R., Scholle F.;
RT "Abrogation of TLR3 inhibition by discrete amino acid changes in the C-
RT terminal half of the West Nile virus NS1 protein.";
RL Virology 456:96-107(2014).
RN [18]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1), AND SUBCELLULAR LOCATION
RP (NON-STRUCTURAL PROTEIN 1).
RX PubMed=24928049; DOI=10.1016/j.virol.2014.04.036;
RA Crook K.R., Miller-Kittrell M., Morrison C.R., Scholle F.;
RT "Modulation of innate immune signaling by the secreted form of the West
RT Nile virus NS1 glycoprotein.";
RL Virology 458:172-182(2014).
RN [19]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP PROTEIN 4A), AND INTERACTION WITH HOST RTN3.
RX PubMed=29117567; DOI=10.1016/j.celrep.2017.10.055;
RA Aktepe T.E., Liebscher S., Prier J.E., Simmons C.P., Mackenzie J.M.;
RT "The host protein reticulon 3.1A is utilized by flaviviruses to facilitate
RT membrane remodelling.";
RL Cell Rep. 21:1639-1654(2017).
RN [20]
RP FUNCTION (SERINE PROTEASE/HELICASE NS3).
RX PubMed=29099073; DOI=10.3390/v9110326;
RA Setoh Y.X., Periasamy P., Peng N.Y.G., Amarilla A.A., Slonchak A.,
RA Khromykh A.A.;
RT "Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition
RT of Type I Interferon Signalling.";
RL Viruses 9:0-0(2017).
RN [21]
RP INTERACTION WITH HUMAN SPCS1.
RX PubMed=29593046; DOI=10.1128/jvi.00197-18;
RA Ma L., Li F., Zhang J.W., Li W., Zhao D.M., Wang H., Hua R.H., Bu Z.G.;
RT "Host Factor SPCS1 Regulates the Replication of Japanese Encephalitis Virus
RT through Interactions with Transmembrane Domains of NS2B.";
RL J. Virol. 92:0-0(2018).
RN [22]
RP MUTAGENESIS OF ASN-444 AND SER-446, AND GLYCOSYLATION AT ASN-444.
RX PubMed=31306420; DOI=10.1371/journal.pntd.0007473;
RA Maharaj P.D., Langevin S.A., Bolling B.G., Andrade C.C., Engle X.A.,
RA Ramey W.N., Bosco-Lauth A., Bowen R.A., Sanders T.A., Huang C.Y.,
RA Reisen W.K., Brault A.C.;
RT "N-linked glycosylation of the West Nile virus envelope protein is not a
RT requisite for avian virulence or vector competence.";
RL PLoS Negl. Trop. Dis. 13:e0007473-e0007473(2019).
RN [23] {ECO:0007744|PDB:2OY0}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2534-2795 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, ACTIVE SITE, AND MUTAGENESIS OF LYS-2589;
RP ASP-2674; LYS-2710 AND GLU-2746.
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 [24] {ECO:0007744|PDB:3I50}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 291-692, AND DISULFIDE BONDS.
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).
RN [25] {ECO:0007744|PDB:3LKZ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2529-2828 IN COMPLEX WITH SIN
RP INHIBITOR, CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE NS5), FUNCTION
RP (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF GLY-2676; ARG-2688;
RP ARG-2691; VAL-2692 AND LEU-2712.
RX PubMed=20685660; DOI=10.1074/jbc.m110.129197;
RA Dong H., Liu L., Zou G., Zhao Y., Li Z., Lim S.P., Shi P.Y., Li H.;
RT "Structural and functional analyses of a conserved hydrophobic pocket of
RT flavivirus methyltransferase.";
RL J. Biol. Chem. 285:32586-32595(2010).
RN [26] {ECO:0007744|PDB:3IYW}
RP STRUCTURE BY ELECTRON MICROSCOPY (13.70 ANGSTROMS) OF 291-690, DISULFIDE
RP BONDS, AND SUBUNIT (ENVELOPE PROTEIN E).
RX PubMed=20956322; DOI=10.1073/pnas.1011036107;
RA Kaufmann B., Vogt M.R., Goudsmit J., Holdaway H.A., Aksyuk A.A.,
RA Chipman P.R., Kuhn R.J., Diamond M.S., Rossmann M.G.;
RT "Neutralization of West Nile virus by cross-linking of its surface proteins
RT with Fab fragments of the human monoclonal antibody CR4354.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18950-18955(2010).
RN [27] {ECO:0007744|PDB:3J0B}
RP STRUCTURE BY ELECTRON MICROSCOPY (10.30 ANGSTROMS) OF 291-690.
RX PubMed=23602814; DOI=10.1016/j.jsb.2013.04.005;
RA Zhang W., Kaufmann B., Chipman P.R., Kuhn R.J., Rossmann M.G.;
RT "Membrane curvature in flaviviruses.";
RL J. Struct. Biol. 183:86-94(2013).
RN [28] {ECO:0007744|PDB:4OIE, ECO:0007744|PDB:4OII}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 963-1143, DISULFIDE BONDS, AND
RP SUBUNIT (NON-STRUCTURAL PROTEIN 1).
RX PubMed=24594604; DOI=10.1073/pnas.1322036111;
RA Edeling M.A., Diamond M.S., Fremont D.H.;
RT "Structural basis of flavivirus NS1 assembly and antibody recognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:4285-4290(2014).
RN [29] {ECO:0007744|PDB:4O6C, ECO:0007744|PDB:4O6D}
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 791-1143, GLYCOSYLATION AT
RP ASN-921; ASN-966 AND ASN-998, DISULFIDE BONDS, AND SUBUNIT (NON-STRUCTURAL
RP PROTEIN 1).
RX PubMed=24505133; DOI=10.1126/science.1247749;
RA Akey D.L., Brown W.C., Dutta S., Konwerski J., Jose J., Jurkiw T.J.,
RA DelProposto J., Ogata C.M., Skiniotis G., Kuhn R.J., Smith J.L.;
RT "Flavivirus NS1 structures reveal surfaces for associations with membranes
RT and the immune system.";
RL Science 343:881-885(2014).
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:0000269|PubMed:17132743, ECO:0000269|PubMed:24245822,
CC ECO:0000269|PubMed:24465392, ECO:0000269|PubMed:24889229,
CC ECO:0000269|PubMed:24928049}.
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 (PubMed:29099073). In addition, NS3 assists the
CC initiation of replication by unwinding the RNA secondary structure in
CC the 3' non-translated region (NTR). Inhibits STAT2 translocation in the
CC nucleus after IFN-alpha treatment (By similarity).
CC {ECO:0000250|UniProtKB:P14335, ECO:0000255|PROSITE-ProRule:PRU00860,
CC ECO:0000269|PubMed:29099073}.
CC -!- FUNCTION: [Non-structural protein 4A]: Facilitates host membrane
CC remodelling necessary for viral replication by interacting with host
CC RTN3. Regulates the ATPase activity of the NS3 helicase activity. NS4A
CC allows NS3 helicase to conserve energy during unwinding.
CC {ECO:0000269|PubMed:19474250, ECO:0000269|PubMed:29117567}.
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 (PubMed:24465392). Inhibits interferon (IFN)-induced host STAT1
CC phosphorylation and nuclear translocation, thereby preventing the
CC establishment of cellular antiviral state by blocking the IFN-
CC alpha/beta pathway (PubMed:15956546). Inhibits STAT2 translocation in
CC the nucleus after IFN-alpha treatment (PubMed:15956546).
CC {ECO:0000269|PubMed:15956546, ECO:0000269|PubMed:24465392}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) genome, and performs the capping of genomes in the cytoplasm
CC (PubMed:19850911). NS5 methylates viral RNA cap at guanine N-7 and
CC ribose 2'-O positions (PubMed:19850911, PubMed:20685660). Besides its
CC role in RNA genome replication, also prevents the establishment of
CC cellular antiviral state by blocking the interferon-alpha/beta (IFN-
CC alpha/beta) signaling pathway (PubMed:20106931). Inhibits host JAK1 and
CC TYK2 phosphorylation, thereby preventing activation of JAK-STAT
CC signaling pathway (PubMed:15650160). {ECO:0000269|PubMed:15650160,
CC ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:20106931,
CC ECO:0000269|PubMed:20685660}.
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:0000269|PubMed:19474250};
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924, ECO:0000269|PubMed:19850911,
CC ECO:0000269|PubMed:20685660};
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase NS5]:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924,
CC ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:20685660};
CC -!- SUBUNIT: [Capsid protein C]: Homodimer (By similarity). Interacts (via
CC N-terminus) with host EXOC1 (via C-terminus); this interaction results
CC in EXOC1 degradation through the proteasome degradation pathway (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi (PubMed:20956322). {ECO:0000269|PubMed:20956322}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (PubMed:24505133, PubMed:24594604). NS1 interacts with NS4B
CC (PubMed:22553322). Interacts with host complement protein CFH; this
CC interaction leads to the degradation of C3 (PubMed:17132743).
CC {ECO:0000269|PubMed:17132743, ECO:0000269|PubMed:22553322,
CC ECO:0000269|PubMed:24505133}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3. May form homooligomers (By similarity). Interacts
CC with human SPCS1 (PubMed:29593046). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:29593046}.
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 4A]: Interacts with host RTN3; this
CC interaction is important to remodel host cell membranes
CC (PubMed:29117567). {ECO:0000269|PubMed:29117567}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with Serine
CC protease/Helicase NS3 (By similarity). Interacts with NS1
CC (PubMed:22553322). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:22553322}.
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).
CC {ECO:0000250|UniProtKB:P17763}.
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:P06935}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:P06935}.
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:0000269|PubMed:24928049}. Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24465392}; Peripheral membrane protein; Lumenal
CC side {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex.
CC {ECO:0000269|PubMed:24465392}.
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:0000269|PubMed:24465392}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex. {ECO:0000269|PubMed:24465392,
CC ECO:0000269|PubMed:29117567}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:24465392}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex.
CC {ECO:0000269|PubMed:24465392}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase NS5]: Host
CC endoplasmic reticulum membrane; Peripheral membrane protein;
CC Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P06935}. 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:0000250|UniProtKB:P06935}.
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 (PubMed:24505133). The
CC excreted form is glycosylated and this is required for efficient
CC secretion of the protein from infected cells (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:24505133}.
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; AF196835; AAF20092.2; -; Genomic_RNA.
DR EMBL; AF404755; AAM81751.1; -; Genomic_RNA.
DR EMBL; HM488125; ADL27936.1; -; Genomic_RNA.
DR EMBL; HM488126; ADL27937.1; -; Genomic_RNA.
DR EMBL; HM488127; ADL27938.1; -; Genomic_RNA.
DR EMBL; HM488128; ADL27939.1; -; Genomic_RNA.
DR EMBL; KC407666; AGI15883.1; -; Genomic_RNA.
DR EMBL; KM083619; AIO10814.1; -; Genomic_RNA.
DR EMBL; KX547386; ANW69091.1; -; Genomic_RNA.
DR EMBL; KX547393; ANW69112.1; -; Genomic_RNA.
DR EMBL; AB185914; BAD34488.1; -; Genomic_RNA.
DR PDB; 2OY0; X-ray; 2.80 A; A/B=2534-2795.
DR PDB; 3I50; X-ray; 3.00 A; E=291-692.
DR PDB; 3IYW; EM; 13.70 A; A/B/C=291-690.
DR PDB; 3J0B; EM; 10.30 A; A/B/C=291-690.
DR PDB; 3LKZ; X-ray; 2.00 A; A/B=2529-2828.
DR PDB; 4O6C; X-ray; 2.75 A; A/B/C/D/E/F=791-1143.
DR PDB; 4O6D; X-ray; 2.59 A; A/B=791-1143.
DR PDB; 4OIE; X-ray; 1.85 A; A=963-1143.
DR PDB; 4OII; X-ray; 3.00 A; A/B=963-1143.
DR PDB; 6UTE; X-ray; 2.90 A; S=593-690.
DR PDBsum; 2OY0; -.
DR PDBsum; 3I50; -.
DR PDBsum; 3IYW; -.
DR PDBsum; 3J0B; -.
DR PDBsum; 3LKZ; -.
DR PDBsum; 4O6C; -.
DR PDBsum; 4O6D; -.
DR PDBsum; 4OIE; -.
DR PDBsum; 4OII; -.
DR PDBsum; 6UTE; -.
DR SMR; Q9Q6P4; -.
DR MEROPS; S07.003; -.
DR iPTMnet; Q9Q6P4; -.
DR ABCD; Q9Q6P4; 16 sequenced antibodies.
DR EvolutionaryTrace; Q9Q6P4; -.
DR Proteomes; UP000096925; Genome.
DR Proteomes; UP000107647; Genome.
DR Proteomes; UP000123900; Genome.
DR Proteomes; UP000138291; Genome.
DR Proteomes; UP000139973; Genome.
DR Proteomes; UP000146770; Genome.
DR Proteomes; UP000163596; Genome.
DR Proteomes; UP000169485; 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: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:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IDA:UniProtKB.
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: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:0039690; P:positive stranded viral RNA replication; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039573; P:suppression by virus of host complement activation; IDA:UniProtKB.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IDA:UniProtKB.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; 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; DP02203; -.
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; 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 STAT1 by virus; Inhibition of host STAT2 by virus;
KW Membrane; Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW RNA-binding; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW Secreted; Serine protease; Suppressor of RNA silencing; Transferase;
KW Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral immunoevasion; Viral penetration into host cytoplasm;
KW Viral RNA replication; Virion; Virus entry into host cell; Zinc.
FT CHAIN 1..3433
FT /note="Genome polyprotein"
FT /id="PRO_0000441576"
FT CHAIN 1..105
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441577"
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:0000250|UniProtKB:P06935"
FT /id="PRO_0000441578"
FT CHAIN 124..290
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441579"
FT CHAIN 124..215
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441580"
FT CHAIN 216..290
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441581"
FT CHAIN 291..791
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441582"
FT CHAIN 792..1143
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441583"
FT CHAIN 1144..1374
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441584"
FT CHAIN 1375..1505
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441585"
FT CHAIN 1506..2124
FT /note="Serine protease/Helicase NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441586"
FT CHAIN 2125..2250
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441587"
FT PEPTIDE 2251..2273
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441588"
FT CHAIN 2274..2528
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441589"
FT CHAIN 2529..3433
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441590"
FT TOPO_DOM 2..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..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..743
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 744..764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 765..770
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 771..791
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 792..1216
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1217..1237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1238..1245
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1246..1268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1269..1288
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1289..1309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1310..1313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1314..1331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1332..1345
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1346..1366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1367..1375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1376..1396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1397..1399
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1400..1420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1421..1477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1478..1498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1499..2174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2175..2195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2196..2200
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2201..2221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2222
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2223..2243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2244..2258
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2259..2279
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2280..2312
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2313..2333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2334..2380
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2381..2401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2402..2444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2445..2465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2466..2470
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2471..2491
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2492..3433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1506..1683
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1686..1842
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1853..2018
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2529..2794
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3058..3210
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 2..15
FT /note="Interaction with host EXOC1"
FT /evidence="ECO:0000250|UniProtKB:P06935"
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 1428..1467
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1690..1693
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT REGION 2169..2173
FT /note="Regulates the ATPase activity of NS3 helicase"
FT /evidence="ECO:0000269|PubMed:19474250"
FT MOTIF 1790..1793
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2917..2919
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT MOTIF 3431..3433
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT ACT_SITE 1556
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1580
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1640
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2589
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:17267492"
FT ACT_SITE 2674
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:17267492"
FT ACT_SITE 2710
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:17267492"
FT ACT_SITE 2746
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000269|PubMed:17267492"
FT BINDING 1699..1706
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2584
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:17267492"
FT BINDING 2614..2615
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0007744|PDB:2OY0"
FT BINDING 2614
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2615
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2632
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2633
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2639
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17267492"
FT BINDING 2659..2660
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0007744|PDB:2OY0"
FT BINDING 2659
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2660
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2674
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17267492"
FT BINDING 2675
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2748
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2972
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 2980
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3245
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3261
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3380
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:0000250|UniProtKB:P06935"
FT SITE 123..124
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 215..216
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 290..291
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 791..792
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1143..1144
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1374..1375
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1505..1506
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1754
FT /note="Inhibition of host STAT1 phosphorylation"
FT /evidence="ECO:0000269|PubMed:29099073"
FT SITE 1963
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1966
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1991
FT /note="Inhibition of host STAT1 phosphorylation"
FT /evidence="ECO:0000269|PubMed:29099073"
FT SITE 2124..2125
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2250..2251
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2273..2274
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2528..2529
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2541
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 2545
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2547
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2552
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:17267492"
FT SITE 2556
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2589
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2674
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2678
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2710
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2741
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2743
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2746
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2584
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 444
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:31306420"
FT CARBOHYD 921
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:24505133"
FT CARBOHYD 966
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:24505133"
FT CARBOHYD 998
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:24505133"
FT DISULFID 293..320
FT /evidence="ECO:0000269|PubMed:20956322"
FT DISULFID 350..411
FT /evidence="ECO:0000269|PubMed:19713934,
FT ECO:0000269|PubMed:20956322"
FT DISULFID 350..406
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 364..395
FT /evidence="ECO:0000269|PubMed:19713934,
FT ECO:0000269|PubMed:20956322"
FT DISULFID 382..411
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 382..406
FT /evidence="ECO:0000269|PubMed:19713934,
FT ECO:0000269|PubMed:20956322"
FT DISULFID 480..578
FT /evidence="ECO:0000269|PubMed:19713934,
FT ECO:0000269|PubMed:20956322"
FT DISULFID 595..626
FT /evidence="ECO:0000269|PubMed:20956322"
FT DISULFID 795..806
FT /evidence="ECO:0000269|PubMed:24505133"
FT DISULFID 846..934
FT /evidence="ECO:0000269|PubMed:24505133"
FT DISULFID 970..1014
FT /evidence="ECO:0000269|PubMed:24505133,
FT ECO:0000269|PubMed:24594604"
FT DISULFID 1071..1120
FT /evidence="ECO:0000269|PubMed:24505133,
FT ECO:0000269|PubMed:24594604"
FT DISULFID 1082..1103
FT /evidence="ECO:0000269|PubMed:24505133,
FT ECO:0000269|PubMed:24594604"
FT DISULFID 1104..1107
FT /evidence="ECO:0000269|PubMed:24505133,
FT ECO:0000269|PubMed:24594604"
FT MUTAGEN 444
FT /note="N->K,S: Complete loss of glycosylation. Attenuated
FT phenotype."
FT /evidence="ECO:0000269|PubMed:31306420"
FT MUTAGEN 446
FT /note="S->F: Complete loss of glycosylation."
FT /evidence="ECO:0000269|PubMed:31306420"
FT MUTAGEN 446
FT /note="S->P: Complete loss of glycosylation. Attenuated
FT phenotype."
FT /evidence="ECO:0000269|PubMed:31306420"
FT MUTAGEN 446
FT /note="S->T: No effect on glycosylation. No effect on avian
FT virulence properties as NYS, but enhanced host oral
FT infectivity."
FT /evidence="ECO:0000269|PubMed:31306420"
FT MUTAGEN 968
FT /note="T->N: No effect on TL3 signaling inhibition by NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 982
FT /note="N->I: No effect on TL3 signaling inhibition by NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1029
FT /note="E->V: No effect on TL3 signaling inhibition by NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1046
FT /note="N->D: Complete loss of TL3 signaling inhibition by
FT NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1086
FT /note="G->R: Almost no effect on TL3 signaling inhibition
FT by NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1108
FT /note="T->I: Complete loss of TL3 signaling inhibition by
FT NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1111
FT /note="P->S: About 50% loss of TL3 signaling inhibition by
FT NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 1124
FT /note="M->V: About 50% loss of TL3 signaling inhibition by
FT NS1."
FT /evidence="ECO:0000269|PubMed:24889229"
FT MUTAGEN 2169..2173
FT /note="EELPD->KKLPK: Complete loss of regulation of the
FT ATPase activity of NS3 helicase by NS4A."
FT /evidence="ECO:0000269|PubMed:19474250"
FT MUTAGEN 2557
FT /note="K->A: 85% loss of NS5-GMP formation."
FT /evidence="ECO:0000269|PubMed:19850911"
FT MUTAGEN 2589
FT /note="K->A,E,R: Complete loss of 2'-O-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2674
FT /note="D->A,N,K: Complete loss of 2'-O-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2676
FT /note="G->A: 86% loss of N7 guanine methyltransferase
FT activity; 60% loss of 2'-O-methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20685660"
FT MUTAGEN 2688
FT /note="R->A: 78% loss of N7 guanine methyltransferase
FT activity; no effect 2'-O-methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20685660"
FT MUTAGEN 2691
FT /note="R->A: 50% loss of N7 guanine methyltransferase
FT activity; no effect 2'-O-methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20685660"
FT MUTAGEN 2692
FT /note="V->A: 10% loss of N7 guanine methyltransferase
FT activity; 50% loss of 2'-O-methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20685660"
FT MUTAGEN 2710
FT /note="K->A,E,N: Complete loss of 2'-O-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT MUTAGEN 2712
FT /note="L->A: 20% loss of N7 guanine methyltransferase
FT activity7; 74% loss of 2'-O-methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20685660"
FT MUTAGEN 2746
FT /note="E->A,D,K: Complete loss of 2'-O-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17267492"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 331..342
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 344..363
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 373..376
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 380..389
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 399..412
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 414..419
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 425..431
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 471..473
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 474..479
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 490..495
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 500..504
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 505..508
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 549..553
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 567..570
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 577..581
FT /evidence="ECO:0007829|PDB:3I50"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:3I50"
FT STRAND 599..603
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 609..611
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 613..619
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 625..627
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 630..637
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 643..649
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 654..666
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 669..679
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 683..689
FT /evidence="ECO:0007829|PDB:6UTE"
FT STRAND 792..798
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 799..801
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 803..813
FT /evidence="ECO:0007829|PDB:4O6D"
FT TURN 816..818
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 819..822
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 823..828
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 830..841
FT /evidence="ECO:0007829|PDB:4O6D"
FT TURN 842..844
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 853..872
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 878..881
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 922..927
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 932..934
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 936..938
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 944..950
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 956..962
FT /evidence="ECO:0007829|PDB:4O6D"
FT HELIX 972..974
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 975..980
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 983..1010
FT /evidence="ECO:0007829|PDB:4OIE"
FT HELIX 1018..1020
FT /evidence="ECO:0007829|PDB:4OIE"
FT HELIX 1029..1031
FT /evidence="ECO:0007829|PDB:4OIE"
FT HELIX 1036..1038
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1061..1069
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1075..1078
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1080..1082
FT /evidence="ECO:0007829|PDB:4O6C"
FT STRAND 1089..1092
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1094..1096
FT /evidence="ECO:0007829|PDB:4O6D"
FT STRAND 1101..1106
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1112..1116
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1119..1122
FT /evidence="ECO:0007829|PDB:4OIE"
FT STRAND 1126..1129
FT /evidence="ECO:0007829|PDB:4OIE"
FT HELIX 2536..2544
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2549..2555
FT /evidence="ECO:0007829|PDB:3LKZ"
FT TURN 2556..2559
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2561..2563
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2566..2574
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2583..2585
FT /evidence="ECO:0007829|PDB:2OY0"
FT HELIX 2586..2595
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2603..2608
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2614..2619
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2625..2631
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2649..2651
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2652..2655
FT /evidence="ECO:0007829|PDB:3LKZ"
FT TURN 2660..2662
FT /evidence="ECO:0007829|PDB:2OY0"
FT STRAND 2669..2673
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2682..2700
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2706..2712
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2717..2730
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2733..2735
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2747..2750
FT /evidence="ECO:0007829|PDB:3LKZ"
FT HELIX 2757..2770
FT /evidence="ECO:0007829|PDB:3LKZ"
FT STRAND 2781..2783
FT /evidence="ECO:0007829|PDB:3LKZ"
SQ SEQUENCE 3433 AA; 381176 MW; A742A68D0E55947E CRC64;
MSKKPGGPGK SRAVNMLKRG MPRVLSLIGL KRAMLSLIDG KGPIRFVLAL LAFFRFTAIA
PTRAVLDRWR GVNKQTAMKH LLSFKKELGT LTSAINRRSS KQKKRGGKTG IAVMIGLIAS
VGAVTLSNFQ GKVMMTVNAT DVTDVITIPT AAGKNLCIVR AMDVGYMCDD TITYECPVLS
AGNDPEDIDC WCTKSAVYVR YGRCTKTRHS RRSRRSLTVQ THGESTLANK KGAWMDSTKA
TRYLVKTESW ILRNPGYALV AAVIGWMLGS NTMQRVVFVV LLLLVAPAYS FNCLGMSNRD
FLEGVSGATW VDLVLEGDSC VTIMSKDKPT IDVKMMNMEA ANLAEVRSYC YLATVSDLST
KAACPTMGEA HNDKRADPAF VCRQGVVDRG WGNGCGLFGK GSIDTCAKFA CSTKAIGRTI
LKENIKYEVA IFVHGPTTVE SHGNYSTQVG ATQAGRFSIT PAAPSYTLKL GEYGEVTVDC
EPRSGIDTNA YYVMTVGTKT FLVHREWFMD LNLPWSSAGS TVWRNRETLM EFEEPHATKQ
SVIALGSQEG ALHQALAGAI PVEFSSNTVK LTSGHLKCRV KMEKLQLKGT TYGVCSKAFK
FLGTPADTGH GTVVLELQYT GTDGPCKVPI SSVASLNDLT PVGRLVTVNP FVSVATANAK
VLIELEPPFG DSYIVVGRGE QQINHHWHKS GSSIGKAFTT TLKGAQRLAA LGDTAWDFGS
VGGVFTSVGK AVHQVFGGAF RSLFGGMSWI TQGLLGALLL WMGINARDRS IALTFLAVGG
VLLFLSVNVH ADTGCAIDIS RQELRCGSGV FIHNDVEAWM DRYKYYPETP QGLAKIIQKA
HKEGVCGLRS VSRLEHQMWE AVKDELNTLL KENGVDLSVV VEKQEGMYKS APKRLTATTE
KLEIGWKAWG KSILFAPELA NNTFVVDGPE TKECPTQNRA WNSLEVEDFG FGLTSTRMFL
KVRESNTTEC DSKIIGTAVK NNLAIHSDLS YWIESRLNDT WKLERAVLGE VKSCTWPETH
TLWGDGILES DLIIPVTLAG PRSNHNRRPG YKTQNQGPWD EGRVEIDFDY CPGTTVTLSE
SCGHRGPATR TTTESGKLIT DWCCRSCTLP PLRYQTDSGC WYGMEIRPQR HDEKTLVQSQ
VNAYNADMID PFQLGLLVVF LATQEVLRKR WTAKISMPAI LIALLVLVFG GITYTDVLRY
VILVGAAFAE SNSGGDVVHL ALMATFKIQP VFMVASFLKA RWTNQENILL MLAAVFFQMA
YHDARQILLW EIPDVLNSLA VAWMILRAIT FTTTSNVVVP LLALLTPGLR CLNLDVYRIL
LLMVGIGSLI REKRSAAAKK KGASLLCLAL ASTGLFNPMI LAAGLIACDP NRKRGWPATE
VMTAVGLMFA IVGGLAELDI DSMAIPMTIA GLMFAAFVIS GKSTDMWIER TADISWESDA
EITGSSERVD VRLDDDGNFQ LMNDPGAPWK IWMLRMVCLA ISAYTPWAIL PSVVGFWITL
QYTKRGGVLW DTPSPKEYKK GDTTTGVYRI MTRGLLGSYQ AGAGVMVEGV FHTLWHTTKG
AALMSGEGRL DPYWGSVKED RLCYGGPWKL QHKWNGQDEV QMIVVEPGKN VKNVQTKPGV
FKTPEGEIGA VTLDFPTGTS GSPIVDKNGD VIGLYGNGVI MPNGSYISAI VQGERMDEPI
PAGFEPEMLR KKQITVLDLH PGAGKTRRIL PQIIKEAINR RLRTAVLAPT RVVAAEMAEA
LRGLPIRYQT SAVPREHNGN EIVDVMCHAT LTHRLMSPHR VPNYNLFVMD EAHFTDPASI
AARGYISTKV ELGEAAAIFM TATPPGTSDP FPESNSPISD LQTEIPDRAW NSGYEWITEY
TGKTVWFVPS VKMGNEIALC LQRAGKKVVQ LNRKSYETEY PKCKNDDWDF VITTDISEMG
ANFKASRVID SRKSVKPTII TEGEGRVILG EPSAVTAASA AQRRGRIGRN PSQVGDEYCY
GGHTNEDDSN FAHWTEARIM LDNINMPNGL IAQFYQPERE KVYTMDGEYR LRGEERKNFL
ELLRTADLPV WLAYKVAAAG VSYHDRRWCF DGPRTNTILE DNNEVEVITK LGERKILRPR
WIDARVYSDH QALKAFKDFA SGKRSQIGLI EVLGKMPEHF MGKTWEALDT MYVVATAEKG
GRAHRMALEE LPDALQTIAL IALLSVMTMG VFFLLMQRKG IGKIGLGGAV LGVATFFCWM
AEVPGTKIAG MLLLSLLLMI VLIPEPEKQR SQTDNQLAVF LICVMTLVSA VAANEMGWLD
KTKSDISSLF GQRIEVKENF SMGEFLLDLR PATAWSLYAV TTAVLTPLLK HLITSDYINT
SLTSINVQAS ALFTLARGFP FVDVGVSALL LAAGCWGQVT LTVTVTAATL LFCHYAYMVP
GWQAEAMRSA QRRTAAGIMK NAVVDGIVAT DVPELERTTP IMQKKVGQIM LILVSLAAVV
VNPSVKTVRE AGILITAAAV TLWENGASSV WNATTAIGLC HIMRGGWLSC LSITWTLIKN
MEKPGLKRGG AKGRTLGEVW KERLNQMTKE EFTRYRKEAI IEVDRSAAKH ARKEGNVTGG
HPVSRGTAKL RWLVERRFLE PVGKVIDLGC GRGGWCYYMA TQKRVQEVRG YTKGGPGHEE
PQLVQSYGWN IVTMKSGVDV FYRPSECCDT LLCDIGESSS SAEVEEHRTI RVLEMVEDWL
HRGPREFCVK VLCPYMPKVI EKMELLQRRY GGGLVRNPLS RNSTHEMYWV SRASGNVVHS
VNMTSQVLLG RMEKRTWKGP QYEEDVNLGS GTRAVGKPLL NSDTSKIKNR IERLRREYSS
TWHHDENHPY RTWNYHGSYD VKPTGSASSL VNGVVRLLSK PWDTITNVTT MAMTDTTPFG
QQRVFKEKVD TKAPEPPEGV KYVLNETTNW LWAFLAREKR PRMCSREEFI RKVNSNAALG
AMFEEQNQWR SAREAVEDPK FWEMVDEERE AHLRGECHTC IYNMMGKREK KPGEFGKAKG
SRAIWFMWLG ARFLEFEALG FLNEDHWLGR KNSGGGVEGL GLQKLGYILR EVGTRPGGKI
YADDTAGWDT RITRADLENE AKVLELLDGE HRRLARAIIE LTYRHKVVKV MRPAADGRTV
MDVISREDQR GSGQVVTYAL NTFTNLAVQL VRMMEGEGVI GPDDVEKLTK GKGPKVRTWL
FENGEERLSR MAVSGDDCVV KPLDDRFATS LHFLNAMSKV RKDIQEWKPS TGWYDWQQVP
FCSNHFTELI MKDGRTLVVP CRGQDELVGR ARISPGAGWN VRDTACLAKS YAQMWLLLYF
HRRDLRLMAN AICSAVPVNW VPTGRTTWSI HAGGEWMTTE DMLEVWNRVW IEENEWMEDK
TPVEKWSDVP YSGKREDIWC GSLIGTRARA TWAENIQVAI NQVRAIIGDE KYVDYMSSLK
RYEDTTLVED TVL
