POLG_DEN1W
ID POLG_DEN1W Reviewed; 3392 AA.
AC P17763; P27910; P89313; P89314;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C;
DE AltName: Full=Capsid protein;
DE AltName: Full=Core protein;
DE Contains:
DE RecName: Full=Protein prM;
DE AltName: Full=Precursor membrane protein;
DE Contains:
DE RecName: Full=Peptide pr;
DE AltName: Full=Peptide precursor;
DE Contains:
DE RecName: Full=Small envelope protein M;
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE Contains:
DE RecName: Full=Non-structural protein 2A;
DE Short=NS2A;
DE Contains:
DE RecName: Full=Serine protease subunit NS2B;
DE AltName: Full=Flavivirin protease NS2B regulatory subunit;
DE AltName: Full=Non-structural protein 2B;
DE Contains:
DE RecName: Full=Serine protease NS3;
DE EC=3.4.21.91;
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Q6P4};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9Q6P4};
DE AltName: Full=Flavivirin protease NS3 catalytic subunit;
DE AltName: Full=Non-structural protein 3;
DE Contains:
DE RecName: Full=Non-structural protein 4A;
DE Short=NS4A;
DE Contains:
DE RecName: Full=Peptide 2k;
DE Contains:
DE RecName: Full=Non-structural protein 4B;
DE Short=NS4B;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase NS5;
DE EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Non-structural protein 5;
OS Dengue virus type 1 (strain Nauru/West Pac/1974) (DENV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11059;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate 45AZ5, and Isolate WestPac;
RX PubMed=9292016; DOI=10.1099/0022-1317-78-9-2287;
RA Puri B., Nelson W.M., Henchal E.A., Hoke C.H., Eckels K.H., Dubois D.R.,
RA Porter K.R., Hayes C.G.;
RT "Molecular analysis of dengue virus attenuation after serial passage in
RT primary dog kidney cells.";
RL J. Gen. Virol. 78:2287-2291(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-1226.
RX PubMed=3672932; DOI=10.1016/0042-6822(87)90196-6;
RA Mason P.W., McAda P.C., Mason T.L., Fournier M.J.;
RT "Sequence of the dengue-1 virus genome in the region encoding the three
RT structural proteins and the major nonstructural protein NS1.";
RL Virology 161:262-267(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-792.
RC STRAIN=Isolate Philippines/836-1/1984;
RX PubMed=2738579; DOI=10.1099/0022-1317-70-7-1701;
RA Chu M.C., O'Rourke E.J., Trent D.W.;
RT "Genetic relatedness among structural protein genes of dengue 1 virus
RT strains.";
RL J. Gen. Virol. 70:1701-1712(1989).
RN [4]
RP SUBUNIT (NON-STRUCTURAL PROTEIN 1).
RX PubMed=2827377; DOI=10.1016/0042-6822(88)90408-4;
RA Winkler G., Randolph V.B., Cleaves G.R., Ryan T.E., Stollar V.;
RT "Evidence that the mature form of the flavivirus nonstructural protein NS1
RT is a dimer.";
RL Virology 162:187-196(1988).
RN [5]
RP PROTEOLYTIC CLEAVAGE (PROTEIN PRM).
RX PubMed=2154882; DOI=10.1016/0042-6822(90)90099-d;
RA Randolph V.B., Winkler G., Stollar V.;
RT "Acidotropic amines inhibit proteolytic processing of flavivirus prM
RT protein.";
RL Virology 174:450-458(1990).
RN [6]
RP GLYCOSYLATION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=8176380; DOI=10.1099/0022-1317-75-5-1183;
RA Pryor M.J., Wright P.J.;
RT "Glycosylation mutants of dengue virus NS1 protein.";
RL J. Gen. Virol. 75:1183-1187(1994).
RN [7]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 1), SUBUNIT (NON-STRUCTURAL
RP PROTEIN 1), AND GLYCOSYLATION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=10364366; DOI=10.1128/jvi.73.7.6104-6110.1999;
RA Flamand M., Megret F., Mathieu M., Lepault J., Rey F.A., Deubel V.;
RT "Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from
RT mammalian cells as a soluble hexamer in a glycosylation-dependent
RT fashion.";
RL J. Virol. 73:6104-6110(1999).
RN [8]
RP PHOSPHORYLATION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=7642575; DOI=10.1074/jbc.270.32.19100;
RA Kapoor M., Zhang L., Ramachandra M., Kusukawa J., Ebner K.E.,
RA Padmanabhan R.;
RT "Association between NS3 and NS5 proteins of dengue virus type 2 in the
RT putative RNA replicase is linked to differential phosphorylation of NS5.";
RL J. Biol. Chem. 270:19100-19106(1995).
RN [9]
RP FUNCTION (PROTEIN PRM), INTERACTION WITH ENVELOPE PROTEIN E (PROTEIN PRM),
RP AND INTERACTION WITH PROTEIN PRM (ENVELOPE PROTEIN E).
RX PubMed=9971841; DOI=10.1128/jvi.73.3.2547-2551.1999;
RA Wang S., He R., Anderson R.;
RT "PrM- and cell-binding domains of the dengue virus E protein.";
RL J. Virol. 73:2547-2551(1999).
RN [10]
RP FUNCTION (SMALL ENVELOPE PROTEIN M).
RX PubMed=13679613; DOI=10.1099/vir.0.19163-0;
RA Catteau A., Kalinina O., Wagner M.C., Deubel V., Courageot M.P.,
RA Despres P.;
RT "Dengue virus M protein contains a proapoptotic sequence referred to as
RT ApoptoM.";
RL J. Gen. Virol. 84:2781-2793(2003).
RN [11]
RP CHARACTERIZATION OF METHYLTRANSFERASE ACTIVITY (RNA-DIRECTED RNA POLYMERASE
RP NS5), AND FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5).
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 [12]
RP FUNCTION (CAPSID PROTEIN C), FUNCTION (ENVELOPE PROTEIN E), AND SUBUNIT
RP (ENVELOPE PROTEIN E).
RX PubMed=11893341; DOI=10.1016/s0092-8674(02)00660-8;
RA Kuhn R.J., Zhang W., Rossmann M.G., Pletnev S.V., Corver J., Lenches E.,
RA Jones C.T., Mukhopadhyay S., Chipman P.R., Strauss E.G., Baker T.S.,
RA Strauss J.H.;
RT "Structure of dengue virus: implications for flavivirus organization,
RT maturation, and fusion.";
RL Cell 108:717-725(2002).
RN [13]
RP DISULFIDE BOND (NON-STRUCTURAL PROTEIN 1).
RC STRAIN=DENV-2 strain Puerto Rico/PR159-S1/1969;
RX PubMed=14981082; DOI=10.1074/jbc.m312907200;
RA Wallis T.P., Huang C.Y., Nimkar S.B., Young P.R., Gorman J.J.;
RT "Determination of the disulfide bond arrangement of dengue virus NS1
RT protein.";
RL J. Biol. Chem. 279:20729-20741(2004).
RN [14]
RP DISULFIDE BOND (ENVELOPE PROTEIN E).
RC STRAIN=DENV-2 strain Thailand/16681/1984;
RX PubMed=14963174; DOI=10.1128/jvi.78.5.2648-2652.2004;
RA Roehrig J.T., Volpe K.E., Squires J., Hunt A.R., Davis B.S., Chang G.J.;
RT "Contribution of disulfide bridging to epitope expression of the dengue
RT type 2 virus envelope glycoprotein.";
RL J. Virol. 78:2648-2652(2004).
RN [15]
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 [16]
RP FUNCTION (SMALL ENVELOPE PROTEIN M).
RX PubMed=16007501; DOI=10.1007/s00232-005-0744-9;
RA Premkumar A., Horan C.R., Gage P.W.;
RT "Dengue virus M protein C-terminal peptide (DVM-C) forms ion channels.";
RL J. Membr. Biol. 204:33-38(2005).
RN [17]
RP INTERACTION WITH SERINE PROTEASE NS3 (RNA-DIRECTED RNA POLYMERASE NS5),
RP INTERACTION WITH RNA-DIRECTED RNA POLYMERASE NS5 (SERINE PROTEASE NS3), AND
RP CATALYTIC ACTIVITY (SERINE PROTEASE NS3).
RC STRAIN=Thailand/NGS-C/1944;
RX PubMed=15917225; DOI=10.1074/jbc.m501393200;
RA Yon C., Teramoto T., Mueller N., Phelan J., Ganesh V.K., Murthy K.H.,
RA Padmanabhan R.;
RT "Modulation of the nucleoside triphosphatase/RNA helicase and 5'-RNA
RT triphosphatase activities of Dengue virus type 2 nonstructural protein 3
RT (NS3) by interaction with NS5, the RNA-dependent RNA polymerase.";
RL J. Biol. Chem. 280:27412-27419(2005).
RN [18]
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 4B (NON-STRUCTURAL PROTEIN 3), AND
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 3 (NON-STRUCTURAL PROTEIN 4B).
RX PubMed=16894199; DOI=10.1099/vir.0.81844-0;
RA Umareddy I., Chao A., Sampath A., Gu F., Vasudevan S.G.;
RT "Dengue virus NS4B interacts with NS3 and dissociates it from single-
RT stranded RNA.";
RL J. Gen. Virol. 87:2605-2614(2006).
RN [19]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 4B), AND TOPOLOGY
RP (NON-STRUCTURAL PROTEIN 4B).
RX PubMed=16436383; DOI=10.1074/jbc.m512697200;
RA Miller S., Sparacio S., Bartenschlager R.;
RT "Subcellular localization and membrane topology of the Dengue virus type 2
RT Non-structural protein 4B.";
RL J. Biol. Chem. 281:8854-8863(2006).
RN [20]
RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5).
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 [21]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 4A), AND TOPOLOGY (PEPTIDE
RP 2K).
RX PubMed=17276984; DOI=10.1074/jbc.m609919200;
RA Miller S., Kastner S., Krijnse-Locker J., Buhler S., Bartenschlager R.;
RT "The non-structural protein 4A of dengue virus is an integral membrane
RT protein inducing membrane alterations in a 2K-regulated manner.";
RL J. Biol. Chem. 282:8873-8882(2007).
RN [22]
RP GLYCOSYLATION AT ASN-347 (ENVELOPE PROTEIN E).
RX PubMed=17459925; DOI=10.1128/jvi.00116-07;
RA Mondotte J.A., Lozach P.Y., Amara A., Gamarnik A.V.;
RT "Essential role of dengue virus envelope protein N glycosylation at
RT asparagine-67 during viral propagation.";
RL J. Virol. 81:7136-7148(2007).
RN [23]
RP REVIEW.
RX PubMed=18644250; DOI=10.1016/j.mib.2008.06.004;
RA Perera R., Kuhn R.J.;
RT "Structural proteomics of dengue virus.";
RL Curr. Opin. Microbiol. 11:369-377(2008).
RN [24]
RP SUBCELLULAR LOCATION (CAPSID PROTEIN C), AND FUNCTION (CAPSID PROTEIN C).
RX PubMed=18420804; DOI=10.1099/vir.0.83264-0;
RA Sangiambut S., Keelapang P., Aaskov J., Puttikhunt C., Kasinrerk W.,
RA Malasit P., Sittisombut N.;
RT "Multiple regions in dengue virus capsid protein contribute to nuclear
RT localization during virus infection.";
RL J. Gen. Virol. 89:1254-1264(2008).
RN [25]
RP FUNCTION (ENVELOPE PROTEIN E), FUNCTION (PROTEIN PRM), AND FUNCTION
RP (PEPTIDE PR).
RX PubMed=18369148; DOI=10.1126/science.1153264;
RA Yu I.M., Zhang W., Holdaway H.A., Li L., Kostyuchenko V.A., Chipman P.R.,
RA Kuhn R.J., Rossmann M.G., Chen J.;
RT "Structure of the immature dengue virus at low pH primes proteolytic
RT maturation.";
RL Science 319:1834-1837(2008).
RN [26]
RP FUNCTION (PROTEIN PR), AND SUBCELLULAR LOCATION (PROTEIN PR).
RX PubMed=19759134; DOI=10.1128/jvi.01637-09;
RA Yu I.M., Holdaway H.A., Chipman P.R., Kuhn R.J., Rossmann M.G., Chen J.;
RT "Association of the pr peptides with dengue virus at acidic pH blocks
RT membrane fusion.";
RL J. Virol. 83:12101-12107(2009).
RN [27]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND INTERACTION WITH HUMAN
RP STAT2 (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=19279106; DOI=10.1128/jvi.02188-08;
RA Ashour J., Laurent-Rolle M., Shi P.Y., Garcia-Sastre A.;
RT "NS5 of dengue virus mediates STAT2 binding and degradation.";
RL J. Virol. 83:5408-5418(2009).
RN [28]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND INTERACTION WITH
RP RNA-DIRECTED RNA POLYMERASE NS5 (SERINE PROTEASE NS3).
RC STRAIN=Thailand/16681/1984;
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 [29]
RP DOMAIN (ENVELOPE PROTEIN E).
RX PubMed=20181718; DOI=10.1128/jvi.01963-09;
RA Hsieh S.C., Tsai W.Y., Wang W.K.;
RT "The length of and nonhydrophobic residues in the transmembrane domain of
RT dengue virus envelope protein are critical for its retention and assembly
RT in the endoplasmic reticulum.";
RL J. Virol. 84:4782-4797(2010).
RN [30]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), AND SUBCELLULAR LOCATION
RP (CAPSID PROTEIN C).
RC STRAIN=DENV-2;
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 [31]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), AND FUNCTION (CAPSID
RP PROTEIN C).
RC STRAIN=DENV-2;
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 [32]
RP REVIEW.
RX PubMed=20372965; DOI=10.1007/s00018-010-0357-z;
RA Rodenhuis-Zybert I.A., Wilschut J., Smit J.M.;
RT "Dengue virus life cycle: viral and host factors modulating infectivity.";
RL Cell. Mol. Life Sci. 67:2773-2786(2010).
RN [33]
RP FUNCTION (CAPSID PROTEIN C).
RX PubMed=21909430; DOI=10.1371/journal.pone.0024365;
RA Colpitts T.M., Barthel S., Wang P., Fikrig E.;
RT "Dengue virus capsid protein binds core histones and inhibits nucleosome
RT formation in human liver cells.";
RL PLoS ONE 6:E24365-E24365(2011).
RN [34]
RP REVIEW (PROTEIN PRM).
RX PubMed=21388812; DOI=10.1016/j.tim.2011.02.002;
RA Rodenhuis-Zybert I.A., Wilschut J., Smit J.M.;
RT "Partial maturation: an immune-evasion strategy of dengue virus?";
RL Trends Microbiol. 19:248-254(2011).
RN [35]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 2A), AND TOPOLOGY
RP (NON-STRUCTURAL PROTEIN 2A).
RC STRAIN=DENV-2 strain NGC;
RX PubMed=23408612; DOI=10.1128/jvi.02424-12;
RA Xie X., Gayen S., Kang C., Yuan Z., Shi P.Y.;
RT "Membrane topology and function of dengue virus NS2A protein.";
RL J. Virol. 87:4609-4622(2013).
RN [36]
RP FUNCTION (SMALL ENVELOPE PROTEIN M), AND FUNCTION (PROTEIN PRM).
RC STRAIN=DENV-1 strain Hawaii;
RX PubMed=25326389; DOI=10.1074/jbc.m114.610428;
RA Hsieh S.C., Wu Y.C., Zou G., Nerurkar V.R., Shi P.Y., Wang W.K.;
RT "Highly conserved residues in the helical domain of dengue virus type 1
RT precursor membrane protein are involved in assembly, precursor membrane
RT (prM) protein cleavage, and entry.";
RL J. Biol. Chem. 289:33149-33160(2014).
RN [37]
RP INTERACTION WITH ENVELOPE PROTEIN E (NON-STRUCTURAL PROTEIN 1), INTERACTION
RP WITH PRM (NON-STRUCTURAL PROTEIN 1), INTERACTION WITH NON-STRUCTURAL
RP PROTEIN 1 (PROTEIN PRM), AND INTERACTION WITH NON-STRUCTURAL PROTEIN 1
RP (ENVELOPE PROTEIN E).
RC STRAIN=DENV-2 strain 16681;
RX PubMed=26562291; DOI=10.1371/journal.ppat.1005277;
RA Scaturro P., Cortese M., Chatel-Chaix L., Fischl W., Bartenschlager R.;
RT "Dengue virus non-structural protein 1 modulates infectious particle
RT production via interaction with the structural proteins.";
RL PLoS Pathog. 11:E1005277-E1005277(2015).
RN [38]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=26655246; DOI=10.1016/j.virol.2015.11.020;
RA Alcala A.C., Medina F., Gonzalez-Robles A., Salazar-Villatoro L.,
RA Fragoso-Soriano R.J., Vasquez C., Cervantes-Salazar M., Del Angel R.M.,
RA Ludert J.E.;
RT "The dengue virus non-structural protein 1 (NS1) is secreted efficiently
RT from infected mosquito cells.";
RL Virology 488:278-287(2015).
RN [39]
RP FUNCTION (NON-STRUCTURAL PROTEIN 2A), AND MUTAGENESIS OF GLY-1138;
RP GLU-1147; GLU-1227; ASP-1252; GLN-1314; LYS-1315 AND GLY-1327.
RX PubMed=25392211; DOI=10.1128/jvi.02882-14;
RA Xie X., Zou J., Puttikhunt C., Yuan Z., Shi P.Y.;
RT "Two distinct sets of NS2A molecules are responsible for dengue virus RNA
RT synthesis and virion assembly.";
RL J. Virol. 89:1298-1313(2015).
RN [40]
RP SUBCELLULAR LOCATION (SERINE PROTEASE SUBUNIT NS2B), AND TOPOLOGY (SERINE
RP PROTEASE SUBUNIT NS2B).
RC STRAIN=DENV-4;
RX PubMed=26072288; DOI=10.1016/j.bbamem.2015.06.010;
RA Li Y., Li Q., Wong Y.L., Liew L.S., Kang C.;
RT "Membrane topology of NS2B of dengue virus revealed by NMR spectroscopy.";
RL Biochim. Biophys. Acta 1848:2244-2252(2015).
RN [41]
RP FUNCTION (SERINE PROTEASE SUBUNIT NS2B), AND SUBUNIT (SERINE PROTEASE
RP SUBUNIT NS2B).
RC STRAIN=DENV-2 New Guinea strain AF0136;
RX PubMed=26728778; DOI=10.1186/s12985-015-0456-4;
RA Leon-Juarez M., Martinez-Castillo M., Shrivastava G., Garcia-Cordero J.,
RA Villegas-Sepulveda N., Mondragon-Castelan M., Mondragon-Flores R.,
RA Cedillo-Barron L.;
RT "Recombinant Dengue virus protein NS2B alters membrane permeability in
RT different membrane models.";
RL Virol. J. 13:1-1(2016).
RN [42]
RP SUBUNIT (RNA-DIRECTED RNA POLYMERASE NS5).
RC STRAIN=DENV-3;
RX PubMed=26895240; DOI=10.1371/journal.ppat.1005451;
RA Klema V.J., Ye M., Hindupur A., Teramoto T., Gottipati K., Padmanabhan R.,
RA Choi K.H.;
RT "Dengue virus nonstructural protein 5 (NS5) assembles into a dimer with a
RT unique methyltransferase and polymerase interface.";
RL PLoS Pathog. 12:E1005451-E1005451(2016).
RN [43]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=27416066; DOI=10.1371/journal.ppat.1005738;
RA Puerta-Guardo H., Glasner D.R., Harris E.;
RT "Dengue virus NS1 disrupts the endothelial glycocalyx, leading to
RT hyperpermeability.";
RL PLoS Pathog. 12:E1005738-E1005738(2016).
RN [44]
RP REVIEW (NON-STRUCTURAL PROTEIN 1).
RX PubMed=27473856; DOI=10.1186/s12985-016-0590-7;
RA Rastogi M., Sharma N., Singh S.K.;
RT "Flavivirus NS1: a multifaceted enigmatic viral protein.";
RL Virol. J. 13:131-131(2016).
RN [45]
RP FUNCTION, INTERACTION WITH HOST MAVS, AND SUBCELLULAR LOCATION.
RX PubMed=27252539; DOI=10.1128/jvi.00221-16;
RA He Z., Zhu X., Wen W., Yuan J., Hu Y., Chen J., An S., Dong X., Lin C.,
RA Yu J., Wu J., Yang Y., Cai J., Li J., Li M.;
RT "Dengue virus subverts host innate immunity by targeting adaptor protein
RT MAVS.";
RL J. Virol. 90:7219-7230(2016).
RN [46]
RP INTERACTION WITH HOST SHFL (SERINE PROTEASE NS3 AND NON-STRUCTURAL PROTEIN
RP 4A).
RC STRAIN=Tonga/74 type 2;
RX PubMed=27974568; DOI=10.1128/jvi.01606-16;
RA Balinsky C.A., Schmeisser H., Wells A.I., Ganesan S., Jin T., Singh K.,
RA Zoon K.C.;
RT "IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity
RT against Dengue Virus, Interacts with MOV10.";
RL J. Virol. 91:0-0(2017).
RN [47]
RP REVIEW (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=28441781; DOI=10.3390/v9040091;
RA El Sahili A., Lescar J.;
RT "Dengue virus non-structural protein 5.";
RL Viruses 9:0-0(2017).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1394-1661, INTERACTION WITH SERINE
RP PROTEASE NS3 (SERINE PROTEASE SUBUNIT NS2B), AND INTERACTION WITH SERINE
RP PROTEASE SUBUNIT NS2B (SERINE PROTEASE NS3).
RX PubMed=20042502; DOI=10.1128/jvi.02044-09;
RA Chandramouli S., Joseph J.S., Daudenarde S., Gatchalian J.,
RA Cornillez-Ty C., Kuhn P.;
RT "Serotype-specific structural differences in the protease-cofactor
RT complexes of the dengue virus family.";
RL J. Virol. 84:3059-3067(2010).
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 (PubMed:11893341).
CC During virus entry, may induce genome penetration into the host
CC cytoplasm after hemifusion induced by the surface proteins. Can migrate
CC to the cell nucleus where it modulates host functions (PubMed:18420804,
CC PubMed:21909430). Overcomes the anti-viral effects of host EXOC1 by
CC sequestering and degrading the latter through the proteasome
CC degradation pathway (PubMed:23522008). {ECO:0000269|PubMed:11893341,
CC ECO:0000269|PubMed:18420804, ECO:0000269|PubMed:21909430,
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:0000269|PubMed:18369148, ECO:0000269|PubMed:19759134}.
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 (PubMed:9971841). prM-E cleavage is
CC inefficient, and many virions are only partially matured. These
CC uncleaved prM would play a role in immune evasion (PubMed:21388812).
CC {ECO:0000269|PubMed:18369148, ECO:0000269|PubMed:25326389,
CC ECO:0000269|PubMed:9971841, ECO:0000303|PubMed:21388812}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding
CC (PubMed:25326389). Exerts cytotoxic effects by activating a
CC mitochondrial apoptotic pathway through M extodomain (PubMed:13679613).
CC May display a viroporin activity (PubMed:16007501).
CC {ECO:0000269|PubMed:13679613, ECO:0000269|PubMed:16007501,
CC ECO:0000269|PubMed:25326389}.
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 (PubMed:18369148).
CC prM-E cleavage is ineficient, and many virions are only partially
CC matured. These uncleaved prM would play a role in immune evasion
CC (PubMed:11893341). {ECO:0000269|PubMed:11893341,
CC ECO:0000269|PubMed:18369148}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 1]: Disrupts the host endothelial
CC glycocalyx layer of host pulmonary microvascular endothelial cells,
CC inducing degradation of sialic acid and shedding of heparan sulfate
CC proteoglycans. NS1 induces expression of sialidases, heparanase, and
CC activates cathepsin L, which activates heparanase via enzymatic
CC cleavage. These effects are probably linked to the endothelial
CC hyperpermeability observed in severe dengue disease.
CC {ECO:0000269|PubMed:27416066}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host immune response. {ECO:0000269|PubMed:25392211}.
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 (PubMed:26728778). {ECO:0000255|PROSITE-
CC ProRule:PRU00859, ECO:0000269|PubMed:26728778}.
CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities:
CC serine protease, NTPase and RNA helicase. NS3 serine protease, in
CC association with NS2B, performs its autocleavage and cleaves the
CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-
CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and
CC unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC during unwinding. Plays a role in the inhibition of the host innate
CC immune response. Interacts with host MAVS and thereby prevents the
CC interaction between DDX58 and MAVS. In turn, IFN-beta production is
CC impaired. Interacts with host AUP1 which mediates induction of
CC lipophagy in host cells and facilitates production of virus progeny
CC particles (By similarity). {ECO:0000250|UniProtKB:P29991,
CC ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000269|PubMed:27252539}.
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:0000269|PubMed:17276984}.
CC -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-
CC derived membrane vesicles where the viral replication takes place (By
CC similarity). Inhibits interferon (IFN)-induced host STAT1
CC phosphorylation and nuclear translocation, thereby preventing the
CC establishment of a cellular antiviral state by blocking the IFN-
CC alpha/beta pathway (PubMed:15956546). {ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:15956546}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O
CC positions. Besides its role in RNA genome replication, also prevents
CC the establishment of cellular antiviral state by blocking the
CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host
CC TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-
CC STAT signaling pathway. {ECO:0000269|PubMed:17267492,
CC ECO:0000269|PubMed:19279106, ECO:0000269|PubMed:19850911}.
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; Evidence={ECO:0000269|PubMed:15917225};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924};
CC -!- SUBUNIT: [Capsid protein C]: Homodimer. Interacts (via N-terminus) with
CC host EXOC1 (via C-terminus) (PubMed:19889084, PubMed:23522008); this
CC interaction results in EXOC1 degradation through the proteasome
CC degradation pathway (PubMed:23522008). {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 (PubMed:9971841).
CC {ECO:0000269|PubMed:9971841}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi (PubMed:11893341). Interacts with protein prM
CC (PubMed:9971841). Interacts with non-structural protein 1
CC (PubMed:26562291). {ECO:0000269|PubMed:11893341,
CC ECO:0000269|PubMed:26562291, ECO:0000269|PubMed:9971841}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (PubMed:2827377, PubMed:10364366). Interacts with envelope
CC protein E (PubMed:26562291). {ECO:0000269|PubMed:10364366,
CC ECO:0000269|PubMed:26562291, ECO:0000269|PubMed:2827377}.
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 (PubMed:20042502). May form homooligomers
CC (PubMed:26728778). {ECO:0000269|PubMed:20042502,
CC ECO:0000269|PubMed:26728778}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B
CC (PubMed:20042502). Interacts with NS4B (PubMed:16894199). Interacts
CC with unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC (PubMed:19850911, PubMed:15917225). Interacts with host SHFL
CC (PubMed:27974568). {ECO:0000269|PubMed:15917225,
CC ECO:0000269|PubMed:16894199, ECO:0000269|PubMed:19850911,
CC ECO:0000269|PubMed:20042502, ECO:0000269|PubMed:27974568}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with host MAVS; this
CC interaction inhibits the synthesis of IFN-beta (PubMed:27252539).
CC Interacts with host SHFL (PubMed:27974568). Interacts with host AUP1;
CC the interaction occurs in the presence of Dengue virus NS4B and induces
CC lipophagy which facilitates production of virus progeny particles (By
CC similarity). {ECO:0000250|UniProtKB:P29991,
CC ECO:0000269|PubMed:27252539, ECO:0000269|PubMed:27974568}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3 (PubMed:16894199). {ECO:0000269|PubMed:16894199}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer
CC (PubMed:26895240). Interacts with host STAT2; this interaction inhibits
CC the phosphorylation of the latter, and, when all viral proteins are
CC present (polyprotein), targets STAT2 for degradation (PubMed:19279106).
CC Interacts with serine protease NS3 (PubMed:15917225, PubMed:19850911).
CC {ECO:0000269|PubMed:15917225, ECO:0000269|PubMed:19279106,
CC ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:26895240}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion. Host nucleus
CC {ECO:0000269|PubMed:18420804}. 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:0000269|PubMed:19759134}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000269|PubMed:9971841}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9971841}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000269|PubMed:20181718}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20181718}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000269|PubMed:10364366, ECO:0000269|PubMed:26655246}. Host
CC endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal
CC side {ECO:0000305}. Note=Located in RE-derived vesicles hosting the
CC replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:23408612}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:23408612}.
CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC reticulum membrane; Multi-pass membrane protein
CC {ECO:0000269|PubMed:26072288}.
CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane
CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side
CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently
CC associated to serine protease subunit NS2B. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:17276984}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:17276984}. Host mitochondrion
CC {ECO:0000269|PubMed:27252539}. Note=Located in RE-associated vesicles
CC hosting the replication complex. Interacts with host MAVS in the
CC mitochondrion-associated endoplasmic reticulum membranes.
CC {ECO:0000269|PubMed:17276984, ECO:0000269|PubMed:27252539}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:16436383}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:16436383}. 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 {ECO:0000305}; Peripheral membrane
CC protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Host nucleus
CC {ECO:0000269|PubMed:16699025}. Note=Located in RE-associated vesicles
CC hosting the replication complex. NS5 protein is mainly localized in the
CC nucleus rather than in ER vesicles, especially in the DENV 2, 3, 4
CC serotypes. {ECO:0000303|PubMed:28441781}.
CC -!- DOMAIN: The transmembrane domains of the small envelope protein M and
CC envelope protein E contain an endoplasmic reticulum retention signal.
CC {ECO:0000269|PubMed:20181718}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Sumoylation of RNA-directed RNA
CC polymerase NS5 increases NS5 protein stability allowing proper viral
CC RNA replication. {ECO:0000250|UniProtKB:P29990}.
CC -!- PTM: [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 the Serine protease NS3. Signal
CC cleavage at the 2K-4B site requires a prior NS3 protease-mediated
CC cleavage at the 4A-2K site.
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:0000269|PubMed:21388812,
CC ECO:0000269|PubMed:2154882}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated (PubMed:8176380,
CC PubMed:10364366). The excreted form is glycosylated and this is
CC required for efficient secretion of the protein from infected cells.
CC {ECO:0000269|PubMed:10364366, ECO:0000269|PubMed:8176380}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Phosphorylated on serines
CC residues. This phosphorylation may trigger NS5 nuclear localization.
CC {ECO:0000269|PubMed:7642575}.
CC -!- PTM: [Envelope protein E]: N-glycosylated.
CC {ECO:0000269|PubMed:17459925}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. mRNA cap 0-1 NS5-type
CC methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}.
CC -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U88535; AAB70694.1; -; Genomic_RNA.
DR EMBL; U88536; AAB70695.1; -; Genomic_RNA.
DR EMBL; M23027; AAA42940.1; -; Genomic_RNA.
DR EMBL; D00503; BAA00395.1; -; Genomic_RNA.
DR PIR; A27032; GNWVWP.
DR RefSeq; NP_059433.1; NC_001477.1.
DR PDB; 3J8D; EM; 26.00 A; B/F=579-675.
DR PDB; 3L6P; X-ray; 2.20 A; A=1476-1648.
DR PDB; 3LKW; X-ray; 2.00 A; A=1476-1657.
DR PDB; 4AL8; X-ray; 1.66 A; C=575-675.
DR PDB; 4GSX; X-ray; 1.90 A; A/B=281-691.
DR PDB; 4GT0; X-ray; 2.57 A; A/B=281-701.
DR PDB; 4LCY; X-ray; 1.60 A; C/J=1741-1749.
DR PDB; 4OIG; X-ray; 2.69 A; A/B/D/E=947-1127.
DR PDB; 5VIC; X-ray; 3.00 A; E=578-676.
DR PDB; 5WJL; X-ray; 3.15 A; C/F/I=1608-1617.
DR PDB; 5WKF; X-ray; 2.95 A; C/H=1608-1617.
DR PDB; 7DWT; EM; 19.00 A; A/B/C=281-775.
DR PDB; 7DWU; EM; 19.00 A; A/B/C=281-775.
DR PDBsum; 3J8D; -.
DR PDBsum; 3L6P; -.
DR PDBsum; 3LKW; -.
DR PDBsum; 4AL8; -.
DR PDBsum; 4GSX; -.
DR PDBsum; 4GT0; -.
DR PDBsum; 4LCY; -.
DR PDBsum; 4OIG; -.
DR PDBsum; 5VIC; -.
DR PDBsum; 5WJL; -.
DR PDBsum; 5WKF; -.
DR PDBsum; 7DWT; -.
DR PDBsum; 7DWU; -.
DR SMR; P17763; -.
DR IntAct; P17763; 1.
DR BindingDB; P17763; -.
DR MEROPS; S07.001; -.
DR ABCD; P17763; 21 sequenced antibodies.
DR GeneID; 5075725; -.
DR KEGG; vg:5075725; -.
DR BRENDA; 3.4.21.91; 9643.
DR EvolutionaryTrace; P17763; -.
DR PRO; PR:P17763; -.
DR Proteomes; UP000002500; 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:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0046762; P:viral budding from endoplasmic reticulum membrane; IDA:UniProtKB.
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 Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 2.60.260.50; -; 1.
DR Gene3D; 2.60.40.350; -; 1.
DR Gene3D; 2.60.98.10; -; 1.
DR Gene3D; 3.30.387.10; -; 1.
DR Gene3D; 3.30.67.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011492; DEAD_Flavivir.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR001122; Flavi_capsidC.
DR InterPro; IPR037172; Flavi_capsidC_sf.
DR InterPro; IPR027287; Flavi_E_Ig-like.
DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR InterPro; IPR001157; Flavi_NS1.
DR InterPro; IPR000752; Flavi_NS2A.
DR InterPro; IPR000487; Flavi_NS2B.
DR InterPro; IPR000404; Flavi_NS4A.
DR InterPro; IPR001528; Flavi_NS4B.
DR InterPro; IPR002535; Flavi_propep.
DR InterPro; IPR038688; Flavi_propep_sf.
DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR InterPro; IPR001850; Flavivirus_NS3_S7.
DR InterPro; IPR014412; Gen_Poly_FLV.
DR InterPro; IPR011998; Glycoprot_cen/dimer.
DR InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01003; Flavi_capsid; 1.
DR Pfam; PF07652; Flavi_DEAD; 1.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF00948; Flavi_NS1; 1.
DR Pfam; PF01005; Flavi_NS2A; 1.
DR Pfam; PF01002; Flavi_NS2B; 1.
DR Pfam; PF01350; Flavi_NS4A; 1.
DR Pfam; PF01349; Flavi_NS4B; 1.
DR Pfam; PF00972; Flavi_NS5; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF00949; Peptidase_S7; 1.
DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF101257; SSF101257; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1.
DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host autophagy by virus; ATP-binding;
KW Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein; Helicase;
KW Host cytoplasm; Host endoplasmic reticulum; Host membrane;
KW Host mitochondrion; Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus;
KW Ion channel; Ion transport; Membrane; Metal-binding; Methyltransferase;
KW mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; Phosphoprotein; Protease; Reference proteome;
KW RNA-binding; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW Secreted; Serine protease; Suppressor of RNA silencing; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation; Viral attachment to host cell;
KW Viral envelope protein; Viral immunoevasion; Viral ion channel;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT CHAIN 1..3392
FT /note="Genome polyprotein"
FT /id="PRO_0000405207"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264658"
FT PROPEP 101..114
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264659"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264660"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264661"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264662"
FT CHAIN 281..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264663"
FT CHAIN 776..1127
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264664"
FT CHAIN 1128..1345
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264666"
FT CHAIN 1346..1475
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264667"
FT CHAIN 1476..2094
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264668"
FT CHAIN 2095..2221
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264669"
FT PEPTIDE 2222..2244
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264670"
FT CHAIN 2245..2493
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264671"
FT CHAIN 2494..3392
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264672"
FT TOPO_DOM 1..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..242
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..725
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 747..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 753..773
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 774..1195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1196..1220
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1221..1226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TRANSMEM 1227..1245
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1246..1269
FT /note="Lumenal"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TRANSMEM 1270..1290
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1291
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TRANSMEM 1292..1310
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1311..1315
FT /note="Lumenal"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TRANSMEM 1316..1336
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1337..1351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TRANSMEM 1352..1370
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26072288"
FT TOPO_DOM 1371
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:26072288"
FT TRANSMEM 1372..1391
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26072288"
FT TOPO_DOM 1392..1447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26072288"
FT INTRAMEM 1448..1468
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26072288"
FT TOPO_DOM 1469..2148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2149..2169
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:17276984"
FT TOPO_DOM 2170..2171
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:17276984"
FT INTRAMEM 2172..2192
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:17276984"
FT TOPO_DOM 2193
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:17276984"
FT TRANSMEM 2194..2214
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:17276984"
FT TOPO_DOM 2215..2229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:17276984"
FT TRANSMEM 2230..2244
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:17276984,
FT ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2245..2276
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16436383"
FT INTRAMEM 2277..2297
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2298..2349
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16436383"
FT TRANSMEM 2350..2370
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2371..2415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16436383"
FT TRANSMEM 2416..2436
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2437..2461
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16436383"
FT TRANSMEM 2462..2482
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2483..3392
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26072288"
FT DOMAIN 1476..1653
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1656..1812
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1822..1988
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2495..2756
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3020..3169
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1..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 378..391
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1398..1437
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1660..1663
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT MOTIF 1760..1763
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2570..2573
FT /note="SUMO-interacting motif"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT ACT_SITE 1526
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1550
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1610
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2554
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2639
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2673
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2709
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1669..1676
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2549
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2579
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2580
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2597
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2598
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2624
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2625
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2640
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2711
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2930
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2934
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2939
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2942
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT SITE 100..101
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 205..206
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT SITE 280..281
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1127..1128
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1345..1346
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1475..1476
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1933
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1936
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2094..2095
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2221..2222
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2244..2245
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2493..2494
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2507
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2510
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2511
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2513
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2518
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2522
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2554
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2639
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2643
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2673
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2704
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2706
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2709
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 905
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 982
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1190
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2303
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2307
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2459
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 283..310
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 340..401
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 354..385
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 372..396
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 465..565
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 582..613
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 779..790
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 830..918
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 954..998
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1055..1104
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1066..1088
FT /evidence="ECO:0000269|PubMed:14981082"
FT DISULFID 1087..1091
FT /evidence="ECO:0000269|PubMed:14981082"
FT VARIANT 125..126
FT /note="HM -> TL (in strain: Isolate Philippines/836-1/
FT 1984)"
FT VARIANT 142
FT /note="S -> P (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 171..173
FT /note="TET -> AEA (in strain: Isolate Philippines/836-1/
FT 1984)"
FT VARIANT 186
FT /note="E -> D (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 210
FT /note="A -> D (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 251
FT /note="A -> G (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 441
FT /note="T -> I (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 475
FT /note="E -> R (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 482
FT /note="E -> K (in strain: Isolate 45AZ5)"
FT VARIANT 573
FT /note="T -> I (in strain: Isolate 45AZ5)"
FT VARIANT 677
FT /note="S -> T (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 786
FT /note="R -> K (in strain: Isolate Philippines/836-1/1984)"
FT VARIANT 1689..1692
FT /note="RRNV -> KRKL (in strain: Isolate 45AZ5)"
FT VARIANT 2242
FT /note="A -> V (in strain: Isolate 45AZ5)"
FT VARIANT 2357
FT /note="F -> L (in strain: Isolate 45AZ5)"
FT VARIANT 2543
FT /note="P -> T (in strain: Isolate 45AZ5)"
FT VARIANT 2779
FT /note="G -> E (in strain: Isolate 45AZ5)"
FT VARIANT 3337
FT /note="R -> Q (in strain: Isolate 45AZ5)"
FT MUTAGEN 1138
FT /note="G->A: Impaired virion assembly."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1147
FT /note="E->A: Impaired virion assembly."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1227
FT /note="E->A: Impaired virion assembly."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1252
FT /note="D->A: Complete loss of viral RNA synthesis."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1314
FT /note="Q->A: Impaired virion assembly."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1315
FT /note="K->A: Impaired virion assembly."
FT /evidence="ECO:0000269|PubMed:25392211"
FT MUTAGEN 1327
FT /note="G->A: Complete loss of viral RNA synthesis."
FT /evidence="ECO:0000269|PubMed:25392211"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 295..308
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 321..332
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 334..352
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 370..379
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 389..409
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 440..444
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:4GSX"
FT TURN 456..458
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 459..467
FT /evidence="ECO:0007829|PDB:4GSX"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 500..504
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:4GSX"
FT HELIX 537..543
FT /evidence="ECO:0007829|PDB:4GSX"
FT TURN 544..546
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 547..553
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 556..559
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 562..571
FT /evidence="ECO:0007829|PDB:4GSX"
FT STRAND 586..590
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 596..598
FT /evidence="ECO:0007829|PDB:4GT0"
FT STRAND 600..606
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 633..635
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 645..649
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 653..663
FT /evidence="ECO:0007829|PDB:4AL8"
FT STRAND 667..673
FT /evidence="ECO:0007829|PDB:4AL8"
FT TURN 956..958
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 960..964
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 967..971
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 973..994
FT /evidence="ECO:0007829|PDB:4OIG"
FT HELIX 1002..1004
FT /evidence="ECO:0007829|PDB:4OIG"
FT HELIX 1013..1015
FT /evidence="ECO:0007829|PDB:4OIG"
FT HELIX 1020..1022
FT /evidence="ECO:0007829|PDB:4OIG"
FT HELIX 1028..1030
FT /evidence="ECO:0007829|PDB:4OIG"
FT HELIX 1043..1045
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1046..1053
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1059..1062
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1073..1076
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1085..1090
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1096..1099
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1104..1106
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1111..1114
FT /evidence="ECO:0007829|PDB:4OIG"
FT STRAND 1396..1402
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1421..1423
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1429..1431
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1496..1504
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1507..1517
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1520..1523
FT /evidence="ECO:0007829|PDB:3LKW"
FT HELIX 1525..1528
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1533..1535
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1538..1540
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1542..1546
FT /evidence="ECO:0007829|PDB:3LKW"
FT TURN 1547..1550
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1551..1557
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1570..1574
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1582..1586
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1589..1593
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1596..1601
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1613..1615
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1621..1625
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1628..1630
FT /evidence="ECO:0007829|PDB:3LKW"
FT STRAND 1636..1639
FT /evidence="ECO:0007829|PDB:3LKW"
SQ SEQUENCE 3392 AA; 378702 MW; 3A7C57D3054D2972 CRC64;
MNNQRKKTGR PSFNMLKRAR NRVSTVSQLA KRFSKGLLSG QGPMKLVMAF IAFLRFLAIP
PTAGILARWG SFKKNGAIKV LRGFKKEISN MLNIMNRRKR SVTMLLMLLP TALAFHLTTR
GGEPHMIVSK QERGKSLLFK TSAGVNMCTL IAMDLGELCE DTMTYKCPRI TETEPDDVDC
WCNATETWVT YGTCSQTGEH RRDKRSVALA PHVGLGLETR TETWMSSEGA WKQIQKVETW
ALRHPGFTVI ALFLAHAIGT SITQKGIIFI LLMLVTPSMA MRCVGIGNRD FVEGLSGATW
VDVVLEHGSC VTTMAKDKPT LDIELLKTEV TNPAVLRKLC IEAKISNTTT DSRCPTQGEA
TLVEEQDTNF VCRRTFVDRG WGNGCGLFGK GSLITCAKFK CVTKLEGKIV QYENLKYSVI
VTVHTGDQHQ VGNETTEHGT TATITPQAPT SEIQLTDYGA LTLDCSPRTG LDFNEMVLLT
MEKKSWLVHK QWFLDLPLPW TSGASTSQET WNRQDLLVTF KTAHAKKQEV VVLGSQEGAM
HTALTGATEI QTSGTTTIFA GHLKCRLKMD KLTLKGMSYV MCTGSFKLEK EVAETQHGTV
LVQVKYEGTD APCKIPFSSQ DEKGVTQNGR LITANPIVTD KEKPVNIEAE PPFGESYIVV
GAGEKALKLS WFKKGSSIGK MFEATARGAR RMAILGDTAW DFGSIGGVFT SVGKLIHQIF
GTAYGVLFSG VSWTMKIGIG ILLTWLGLNS RSTSLSMTCI AVGMVTLYLG VMVQADSGCV
INWKGRELKC GSGIFVTNEV HTWTEQYKFQ ADSPKRLSAA IGKAWEEGVC GIRSATRLEN
IMWKQISNEL NHILLENDMK FTVVVGDVSG ILAQGKKMIR PQPMEHKYSW KSWGKAKIIG
ADVQNTTFII DGPNTPECPD NQRAWNIWEV EDYGFGIFTT NIWLKLRDSY TQVCDHRLMS
AAIKDSKAVH ADMGYWIESE KNETWKLARA SFIEVKTCIW PKSHTLWSNG VLESEMIIPK
IYGGPISQHN YRPGYFTQTA GPWHLGKLEL DFDLCEGTTV VVDEHCGNRG PSLRTTTVTG
KTIHEWCCRS CTLPPLRFKG EDGCWYGMEI RPVKEKEENL VKSMVSAGSG EVDSFSLGLL
CISIMIEEVM RSRWSRKMLM TGTLAVFLLL TMGQLTWNDL IRLCIMVGAN ASDKMGMGTT
YLALMATFRM RPMFAVGLLF RRLTSREVLL LTVGLSLVAS VELPNSLEEL GDGLAMGIMM
LKLLTDFQSH QLWATLLSLT FVKTTFSLHY AWKTMAMILS IVSLFPLCLS TTSQKTTWLP
VLLGSLGCKP LTMFLITENK IWGRKSWPLN EGIMAVGIVS ILLSSLLKND VPLAGPLIAG
GMLIACYVIS GSSADLSLEK AAEVSWEEEA EHSGASHNIL VEVQDDGTMK IKDEERDDTL
TILLKATLLA ISGVYPMSIP ATLFVWYFWQ KKKQRSGVLW DTPSPPEVER AVLDDGIYRI
LQRGLLGRSQ VGVGVFQEGV FHTMWHVTRG AVLMYQGKRL EPSWASVKKD LISYGGGWRF
QGSWNAGEEV QVIAVEPGKN PKNVQTAPGT FKTPEGEVGA IALDFKPGTS GSPIVNREGK
IVGLYGNGVV TTSGTYVSAI AQAKASQEGP LPEIEDEVFR KRNLTIMDLH PGSGKTRRYL
PAIVREAIRR NVRTLVLAPT RVVASEMAEA LKGMPIRYQT TAVKSEHTGK EIVDLMCHAT
FTMRLLSPVR VPNYNMIIMD EAHFTDPASI AARGYISTRV GMGEAAAIFM TATPPGSVEA
FPQSNAVIQD EERDIPERSW NSGYDWITDF PGKTVWFVPS IKSGNDIANC LRKNGKRVVQ
LSRKTFDTEY QKTKNNDWDY VVTTDISEMG ANFRADRVID PRRCLKPVIL KDGPERVILA
GPMPVTVASA AQRRGRIGRN QNKEGDQYIY MGQPLNNDED HAHWTEAKML LDNINTPEGI
IPALFEPERE KSAAIDGEYR LRGEARKTFV ELMRRGDLPV WLSYKVASEG FQYSDRRWCF
DGERNNQVLE ENMDVEIWTK EGERKKLRPR WLDARTYSDP LALREFKEFA AGRRSVSGDL
ILEIGKLPQH LTQRAQNALD NLVMLHNSEQ GGKAYRHAME ELPDTIETLM LLALIAVLTG
GVTLFFLSGR GLGKTSIGLL CVIASSALLW MASVEPHWIA ASIILEFFLM VLLIPEPDRQ
RTPQDNQLAY VVIGLLFMIL TAAANEMGLL ETTKKDLGIG HAAAENHHHA AMLDVDLHPA
SAWTLYAVAT TIITPMMRHT IENTTANISL TAIANQAAIL MGLDKGWPIS KMDIGVPLLA
LGCYSQVNPL TLTAAVFMLV AHYAIIGPGL QAKATREAQK RTAAGIMKNP TVDGIVAIDL
DPVVYDAKFE KQLGQIMLLI LCTSQILLMR TTWALCESIT LATGPLTTLW EGSPGKFWNT
TIAVSMANIF RGSYLAGAGL AFSLMKSLGG GRRGTGAQGE TLGEKWKRQL NQLSKSEFNT
YKRSGIIEVD RSEAKEGLKR GEPTKHAVSR GTAKLRWFVE RNLVKPEGKV IDLGCGRGGW
SYYCAGLKKV TEVKGYTKGG PGHEEPIPMA TYGWNLVKLY SGKDVFFTPP EKCDTLLCDI
GESSPNPTIE EGRTLRVLKM VEPWLRGNQF CIKILNPYMP SVVETLEQMQ RKHGGMLVRN
PLSRNSTHEM YWVSCGTGNI VSAVNMTSRM LLNRFTMAHR KPTYERDVDL GAGTRHVAVE
PEVANLDIIG QRIENIKNGH KSTWHYDEDN PYKTWAYHGS YEVKPSGSAS SMVNGVVRLL
TKPWDVIPMV TQIAMTDTTP FGQQRVFKEK VDTRTPKAKR GTAQIMEVTA RWLWGFLSRN
KKPRICTREE FTRKVRSNAA IGAVFVDENQ WNSAKEAVED ERFWDLVHRE RELHKQGKCA
TCVYNMMGKR EKKLGEFGKA KGSRAIWYMW LGARFLEFEA LGFMNEDHWF SRENSLSGVE
GEGLHKLGYI LRDISKIPGG NMYADDTAGW DTRITEDDLQ NEAKITDIME PEHALLATSI
FKLTYQNKVV RVQRPAKNGT VMDVISRRDQ RGSGQVGTYG LNTFTNMEAQ LIRQMESEGI
FSPSELETPN LAERVLDWLK KHGTERLKRM AISGDDCVVK PIDDRFATAL TALNDMGKVR
KDIPQWEPSK GWNDWQQVPF CSHHFHQLIM KDGREIVVPC RNQDELVGRA RVSQGAGWSL
RETACLGKSY AQMWQLMYFH RRDLRLAANA ICSAVPVDWV PTSRTTWSIH AHHQWMTTED
MLSVWNRVWI EENPWMEDKT HVSSWEDVPY LGKREDRWCG SLIGLTARAT WATNIQVAIN
QVRRLIGNEN YLDFMTSMKR FKNESDPEGA LW
