ID POLG_YEFV1 Reviewed; 3411 AA. AC P03314; O42028; O91857; P19901; Q102J3; Q45RQ2; Q89275; Q89276; Q9W878; AC Q9YWN0; Q9YWN1; Q9YWN2; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 04-NOV-2026, entry version 222. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Capsid protein C; DE AltName: Full=Core protein; DE Contains: DE RecName: Full=Protein prM; DE Contains: DE RecName: Full=Peptide pr; DE Contains: DE RecName: Full=Small envelope protein M; DE AltName: Full=Matrix protein; DE Contains: DE RecName: Full=Envelope protein E; DE Contains: DE RecName: Full=Non-structural protein 1; DE Short=NS1; DE Contains: DE RecName: Full=Non-structural protein 2A; DE Short=NS2A; DE Contains: DE RecName: Full=Serine protease subunit NS2B; DE AltName: Full=Flavivirin protease NS2B regulatory subunit; DE AltName: Full=Non-structural protein 2B; DE Contains: DE RecName: Full=Serine protease NS3; DE EC=3.4.21.91 {ECO:0000269|PubMed:21419753}; DE EC=3.6.1.15 {ECO:0000269|PubMed:16051820}; DE EC=3.6.4.13 {ECO:0000269|PubMed:16051820}; 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/Methyltransferase 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 Yellow fever virus (strain 17D vaccine) (YFV). OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes; OC Amarillovirales; Flaviviridae; Orthoflavivirus; Euflavivirus; OC Orthoflavivirus flavi. OX NCBI_TaxID=11090; OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti). OH NCBI_TaxID=299629; Aedes luteocephalus (Mosquito). OH NCBI_TaxID=7161; Aedes simpsoni. OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=314293; Simiiformes. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=4023707; DOI=10.1126/science.4023707; RA Rice C.M., Lenches E.M., Eddy S.R., Shin S.J., Sheets R.L., Strauss J.H.; RT "Nucleotide sequence of yellow fever virus: implications for flavivirus RT gene expression and evolution."; RL Science 229:726-733(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate 17D-213 vaccine, and Isolate 17DD vaccine; RX PubMed=7754673; DOI=10.1016/0168-1702(94)00076-o; RA dos Santos C.N., Post P.R., Carvalho R., Ferreira I.I., Rice C.M., RA Galler R.; RT "Complete nucleotide sequence of yellow fever virus vaccine strains 17DD RT and 17D-213."; RL Virus Res. 35:35-41(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate 17D-204-USA HONG1 vaccine, Isolate 17D-204-USA HONG2 RC vaccine, and Isolate 17D-204-USA HONG3 vaccine; RX PubMed=9712515; DOI=10.1016/s0168-1702(98)00036-7; RA Xie H., Cass A.R., Barrett A.D.T.; RT "Yellow fever 17D vaccine virus isolated from healthy vaccinees accumulates RT very few mutations."; RL Virus Res. 55:93-99(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate Pasteur 17D-204 vaccine; RX PubMed=2734112; DOI=10.1093/nar/17.10.3989; RA Dupuy A., Despres P., Cahour A., Girard M., Bouloy M.; RT "Nucleotide sequence comparison of the genome of two 17D-204 yellow fever RT vaccines."; RL Nucleic Acids Res. 17:3989-3989(1989). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate 17D-204-South Africa vaccine, Isolate 17D-204-South RC Africa vaccine large plaque variant, and Isolate 17D-204-South Africa RC vaccine medium plaque variant; RX PubMed=9714237; DOI=10.1099/0022-1317-79-8-1895; RA Xie H., Ryman K.D., Campbell G.A., Barrett A.D.T.; RT "Mutation in NS5 protein attenuates mouse neurovirulence of yellow fever RT 17D vaccine virus."; RL J. Gen. Virol. 79:1895-1899(1998). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate Spain/AVD2791-93F/2004 vaccine; RX PubMed=16597510; DOI=10.1016/j.jcv.2006.02.005; RA Doblas A., Domingo C., Bae H.G., Bohorquez C.L., de Ory F., Niedrig M., RA Mora D., Carrasco F.J., Tenorio A.; RT "Yellow fever vaccine-associated viscerotropic disease and death in RT Spain."; RL J. Clin. Virol. 36:156-158(2006). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate Brazil/YF-VAVD/1975 vaccine; RX PubMed=16464518; DOI=10.1016/j.vaccine.2006.01.009; RA Engel A.R., Vasconcelos P.F., McArthur M.A., Barrett A.D.; RT "Characterization of a viscerotropic yellow fever vaccine variant from a RT patient in Brazil."; RL Vaccine 24:2803-2809(2006). RN [8] RP PROTEIN SEQUENCE OF 779-798; 1485-1497 AND 2507-2510, AND PROTEOLYTIC RP CLEAVAGE (GENOME POLYPROTEIN). RX PubMed=3008425; DOI=10.1016/0042-6822(86)90098-x; RA Rice C.M., Aebersold R., Teplow D.B., Pata J., Bell J.R., Vorndam A.V., RA Trent D.W., Brandriss M.W., Schlesinger J.J., Strauss J.H.; RT "Partial N-terminal amino acid sequences of three nonstructural proteins of RT two flaviviruses."; RL Virology 151:1-9(1986). RN [9] RP PROTEIN SEQUENCE OF 2257-2276. RX PubMed=2922923; DOI=10.1016/0042-6822(89)90045-7; RA Chambers T.J., McCourt D.W., Rice C.M.; RT "Yellow fever virus proteins NS2A, NS2B, and NS4B: identification and RT partial N-terminal amino acid sequence analysis."; RL Virology 169:100-109(1989). RN [10] RP PROTEIN SEQUENCE OF 102-121, AND PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN). RX PubMed=8189517; DOI=10.1128/jvi.68.6.3794-3802.1994; RA Amberg S.M., Nestorowicz A., McCourt D.W., Rice C.M.; RT "NS2B-3 proteinase-mediated processing in the yellow fever virus structural RT region: in vitro and in vivo studies."; RL J. Virol. 68:3794-3802(1994). RN [11] RP CHARACTERIZATION (SERINE PROTEASE NS3), AND MUTAGENESIS OF HIS-1537; RP ASP-1561 AND SER-1622. RX PubMed=2147282; DOI=10.1073/pnas.87.22.8898; RA Chambers T.J., Weir R.C., Grakoui A., McCourt D.W., Bazan J.F., RA Fletterick R.J., Rice C.M.; RT "Evidence that the N-terminal domain of nonstructural protein NS3 from RT yellow fever virus is a serine protease responsible for site-specific RT cleavages in the viral polyprotein."; RL Proc. Natl. Acad. Sci. U.S.A. 87:8898-8902(1990). RN [12] RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN). RX PubMed=1833562; DOI=10.1128/jvi.65.11.6042-6050.1991; RA Chambers T.J., Grakoui A., Rice C.M.; RT "Processing of the yellow fever virus nonstructural polyprotein: a RT catalytically active NS3 proteinase domain and NS2B are required for RT cleavages at dibasic sites."; RL J. Virol. 65:6042-6050(1991). RN [13] RP CHARACTERIZATION (SERINE PROTEASE NS3). RX PubMed=7853494; DOI=10.1128/jvi.69.3.1600-1605.1995; RA Chambers T.J., Nestorowicz A., Rice C.M.; RT "Mutagenesis of the yellow fever virus NS2B/3 cleavage site: determinants RT of cleavage site specificity and effects on polyprotein processing and RT viral replication."; RL J. Virol. 69:1600-1605(1995). RN [14] RP MUTAGENESIS OF ARG-2107; ARG-2505 AND ARG-2506, AND PROTEOLYTIC CLEAVAGE RP (GENOME POLYPROTEIN). RX PubMed=8421901; DOI=10.1006/viro.1993.1076; RA Lin C., Chambers T.J., Rice C.M.; RT "Mutagenesis of conserved residues at the yellow fever virus 3/4A and 4B/5 RT dibasic cleavage sites: effects on cleavage efficiency and polyprotein RT processing."; RL Virology 192:596-604(1993). RN [15] RP MUTAGENESIS OF ARG-2107; SER-2234 AND ARG-2506, AND PROTEOLYTIC CLEAVAGE RP (GENOME POLYPROTEIN). RX PubMed=8445732; DOI=10.1128/jvi.67.4.2327-2335.1993; RA Lin C., Amberg S.M., Chambers T.J., Rice C.M.; RT "Cleavage at a novel site in the NS4A region by the yellow fever virus RT NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B RT signalase site."; RL J. Virol. 67:2327-2335(1993). RN [16] RP MUTAGENESIS OF PHE-1351; GLY-1352; ARG-1353; ARG-1354 AND SER-1355, AND RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN). RX PubMed=8116234; DOI=10.1006/viro.1994.1103; RA Nestorowicz A., Chambers T.J., Rice C.M.; RT "Mutagenesis of the yellow fever virus NS2A/2B cleavage site: effects on RT proteolytic processing, viral replication, and evidence for alternative RT processing of the NS2A protein."; RL Virology 199:114-123(1994). RN [17] RP MUTAGENESIS OF ASN-908; SER-910; ASN-986 AND THR-988. RX PubMed=8806496; DOI=10.1006/viro.1996.0406; RA Muylaert I.R., Chambers T.J., Galler R., Rice C.M.; RT "Mutagenesis of the N-linked glycosylation sites of the yellow fever virus RT NS1 protein: effects on virus replication and mouse neurovirulence."; RL Virology 222:159-168(1996). RN [18] RP MUTAGENESIS OF ARG-1077. RX PubMed=8985349; DOI=10.1128/jvi.71.1.291-298.1997; RA Muylaert I.R., Galler R., Rice C.M.; RT "Genetic analysis of the yellow fever virus NS1 protein: identification of RT a temperature-sensitive mutation which blocks RNA accumulation."; RL J. Virol. 71:291-298(1997). RN [19] RP FUNCTION (NON-STRUCTURAL PROTEIN 1). RX PubMed=9371625; DOI=10.1128/jvi.71.12.9608-9617.1997; RA Lindenbach B.D., Rice C.M.; RT "Trans-complementation of yellow fever virus NS1 reveals a role in early RT RNA replication."; RL J. Virol. 71:9608-9617(1997). RN [20] RP PHOSPHORYLATION (RNA-DIRECTED RNA POLYMERASE/METHYLTRANSFERASE NS5). RX PubMed=9621090; DOI=10.1128/jvi.72.7.6199-6206.1998; RA Reed K.E., Gorbalenya A.E., Rice C.M.; RT "The NS5A/NS5 proteins of viruses from three genera of the family RT flaviviridae are phosphorylated by associated serine/threonine kinases."; RL J. Virol. 72:6199-6206(1998). RN [21] RP INTERACTION WITH NON-STRUCTURAL PROTEIN 4A (NON-STRUCTURAL PROTEIN 1), AND RP INTERACTION WITH NON-STRUCTURAL PROTEIN 1 (NON-STRUCTURAL PROTEIN 4A). RX PubMed=10233920; DOI=10.1128/jvi.73.6.4611-4621.1999; RA Lindenbach B.D., Rice C.M.; RT "Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a RT determinant of replicase function."; RL J. Virol. 73:4611-4621(1999). RN [22] RP MUTAGENESIS OF 99-ARG--ARG-101. RX PubMed=10482557; DOI=10.1128/jvi.73.10.8083-8094.1999; RA Amberg S.M., Rice C.M.; RT "Mutagenesis of the NS2B-NS3-mediated cleavage site in the flavivirus RT capsid protein demonstrates a requirement for coordinated processing."; RL J. Virol. 73:8083-8094(1999). RN [23] RP MUTAGENESIS OF 116-LEU--GLY-121. RX PubMed=10590087; DOI=10.1128/jvi.74.1.24-32.2000; RA Lee E., Stocks C.E., Amberg S.M., Rice C.M., Lobigs M.; RT "Mutagenesis of the signal sequence of yellow fever virus prM protein: RT enhancement of signalase cleavage In vitro is lethal for virus RT production."; RL J. Virol. 74:24-32(2000). RN [24] RP MUTAGENESIS OF 1406-GLU--LYS-1409. RX PubMed=10998334; DOI=10.1006/viro.2000.0488; RA Droll D.A., Krishna Murthy H.M., Chambers T.J.; RT "Yellow fever virus NS2B-NS3 protease: charged-to-alanine mutagenesis and RT deletion analysis define regions important for protease complex formation RT and function."; RL Virology 275:335-347(2000). RN [25] RP MUTAGENESIS OF 1319-GLN--THR-1321, AND PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL RP PROTEIN 2A). RX PubMed=11967294; DOI=10.1128/jvi.76.10.4773-4784.2002; RA Kummerer B.M., Rice C.M.; RT "Mutations in the yellow fever virus nonstructural protein NS2A selectively RT block production of infectious particles."; RL J. Virol. 76:4773-4784(2002). RN [26] RP SUBUNIT (CAPSID PROTEIN C). RX PubMed=12768036; DOI=10.1128/jvi.77.12.7143-7149.2003; RA Jones C.T., Ma L., Burgner J.W., Groesch T.D., Post C.B., Kuhn R.J.; RT "Flavivirus capsid is a dimeric alpha-helical protein."; RL J. Virol. 77:7143-7149(2003). RN [27] RP SUBCELLULAR LOCATION (SMALL ENVELOPE PROTEIN M), AND SUBCELLULAR LOCATION RP (ENVELOPE PROTEIN E). RX PubMed=15507646; DOI=10.1128/jvi.78.22.12591-12602.2004; RA Op De Beeck A., Rouille Y., Caron M., Duvet S., Dubuisson J.; RT "The transmembrane domains of the prM and E proteins of yellow fever virus RT are endoplasmic reticulum localization signals."; RL J. Virol. 78:12591-12602(2004). RN [28] 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 [29] RP PHOSPHORYLATION AT SER-2562, AND MUTAGENESIS OF SER-2562. RX PubMed=18757072; DOI=10.1016/j.virol.2008.07.013; RA Bhattacharya D., Hoover S., Falk S.P., Weisblum B., Vestling M., RA Striker R.; RT "Phosphorylation of yellow fever virus NS5 alters methyltransferase RT activity."; RL Virology 380:276-284(2008). RN [30] RP FUNCTION (SERINE PROTEASE NS3), AND MUTAGENESIS OF TRP-1833. RX PubMed=18199634; DOI=10.1128/jvi.02447-07; RA Patkar C.G., Kuhn R.J.; RT "Yellow Fever virus NS3 plays an essential role in virus assembly RT independent of its known enzymatic functions."; RL J. Virol. 82:3342-3352(2008). RN [31] RP FUNCTION (RNA-DIRECTED RNA POLYMERASE/METHYLTRANSFERASE NS5). 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 [32] RP INTERACTION WITH HUMAN PDCD6IP (SERINE PROTEASE NS3). RX PubMed=21044891; DOI=10.1016/j.micinf.2010.10.010; RA Carpp L.N., Galler R., Bonaldo M.C.; RT "Interaction between the yellow fever virus nonstructural protein NS3 and RT the host protein Alix contributes to the release of infectious particles."; RL Microbes Infect. 13:85-95(2011). RN [33] RP BIOPHYSICOCHEMICAL PROPERTIES (SERINE PROTEASE NS3), CATALYTIC ACTIVITY RP (SERINE PROTEASE NS3), AND PROTEOLYTIC CLEAVAGE (POLYPROTEIN). RX PubMed=21419753; DOI=10.1016/j.bbrc.2011.03.054; RA Kondo M.Y., Oliveira L.C., Okamoto D.N., de Araujo M.R., RA Duarte dos Santos C.N., Juliano M.A., Juliano L., Gouvea I.E.; RT "Yellow fever virus NS2B/NS3 protease: hydrolytic properties and substrate RT specificity."; RL Biochem. Biophys. Res. Commun. 407:640-644(2011). RN [34] RP FUNCTION (RNA-DIRECTED RNA POLYMERASE/METHYLTRANSFERASE NS5), RP UBIQUITINATION AT LYS-5 (RNA-DIRECTED RNA POLYMERASE/METHYLTRANSFERASE RP NS5), INTERACTION WITH HOST STAT2 (RNA-DIRECTED RNA RP POLYMERASE/METHYLTRANSFERASE NS5), MUTAGENESIS OF LYS-2512, AND INTERACTION RP WITH HOST TRIM23 (RNA-DIRECTED RNA POLYMERASE/METHYLTRANSFERASE NS5). RX PubMed=25211074; DOI=10.1016/j.chom.2014.07.015; RA Laurent-Rolle M., Morrison J., Rajsbaum R., Macleod J.M., Pisanelli G., RA Pham A., Ayllon J., Miorin L., Martinez-Romero C., tenOever B.R., RA Garcia-Sastre A.; RT "The interferon signaling antagonist function of yellow fever virus NS5 RT protein is activated by type I interferon."; RL Cell Host Microbe 16:314-327(2014). RN [35] RP INTERACTION WITH SERINE PROTEASE NS3 (NON-STRUCTURAL PROTEIN 2A), RP INTERACTION WITH NON-STRUCTURAL PROTEIN 2A (SERINE PROTEASE NS3), RP MUTAGENESIS OF 1152-ARG--ARG-1154; 1229-ARG--ARG-1231 AND GLN-1319, AND RP TOPOLOGY (NON-STRUCTURAL PROTEIN 2A). RX PubMed=25694595; DOI=10.1128/jvi.03351-14; RA Vossmann S., Wieseler J., Kerber R., Kuemmerer B.M.; RT "A basic cluster in the N terminus of yellow fever virus NS2A contributes RT to infectious particle production."; RL J. Virol. 89:4951-4965(2015). RN [36] RP FUNCTION (CAPSID PROTEIN C). RX PubMed=27849599; DOI=10.1073/pnas.1600544113; RA Samuel G.H., Wiley M.R., Badawi A., Adelman Z.N., Myles K.M.; RT "Yellow fever virus capsid protein is a potent suppressor of RNA silencing RT that binds double-stranded RNA."; RL Proc. Natl. Acad. Sci. U.S.A. 113:13863-13868(2016). RN [37] RP FUNCTION (ENVELOPE PROTEIN E), AND INTERACTION WITH HOST LRP1; LRP4 AND RP VLDLR (ENVELOPE PROTEIN E). RX PubMed=41162706; DOI=10.1038/s41586-025-09689-2; RA Chong Z., Hui S., Qiu X., Palakurty S., Sariol A., Kaszuba T., Nguyen M.N., RA Li P., Raju S., Hall P.D., Nelson C.A., Baltazar-Perez I., Price D.A., RA Rothlauf P.W., Crowe J.E., Whelan S.P.J., Leung D.W., Amarasinghe G.K., RA Bailey A.L., Fremont D.H., Diamond M.S.; RT "Multiple LDLR family members act as entry receptors for yellow fever RT virus."; RL Nature 0:0-0(2025). RN [38] RP STRUCTURE BY ELECTRON MICROSCOPY OF IMMATURE PARTICLES, AND SUBUNIT RP (ENVELOPE PROTEIN E). RX PubMed=12773377; DOI=10.1093/emboj/cdg270; RA Zhang Y., Corver J., Chipman P.R., Zhang W., Pletnev S.V., Sedlak D., RA Baker T.S., Strauss J.H., Kuhn R.J., Rossmann M.G.; RT "Structures of immature flavivirus particles."; RL EMBO J. 22:2604-2613(2003). RN [39] RP X-RAY CRYSTALLOGRAPHY, AND CATALYTIC ACTIVITY (SERINE PROTEASE NS3). RX PubMed=16051820; DOI=10.1128/jvi.79.16.10268-10277.2005; RA Wu J., Bera A.K., Kuhn R.J., Smith J.L.; RT "Structure of the Flavivirus helicase: implications for catalytic activity, RT protein interactions, and proteolytic processing."; RL J. Virol. 79:10268-10277(2005). RN [40] {ECO:0007744|PDB:3EVA, ECO:0007744|PDB:3EVB, ECO:0007744|PDB:3EVC, ECO:0007744|PDB:3EVD, ECO:0007744|PDB:3EVE, ECO:0007744|PDB:3EVF} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH GTP; RP GUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE; RP P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE AND RP S-ADENOSYL-L-HOMOCYSTEINE. RX PubMed=19101564; DOI=10.1016/j.jmb.2008.11.058; RA Geiss B.J., Thompson A.A., Andrews A.J., Sons R.L., Gari H.H., Keenan S.M., RA Peersen O.B.; RT "Analysis of flavivirus NS5 methyltransferase cap binding."; RL J. Mol. Biol. 385:1643-1654(2009). CC -!- FUNCTION: [Capsid protein C]: Capsid protein C self-assembles to form CC an icosahedral capsid about 30 nm in diameter. The capsid encapsulates CC the genomic RNA (Probable). Plays a role in virus budding by binding to CC the cell membrane and gathering the viral RNA into a nucleocapsid that CC 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. {ECO:0000250|UniProtKB:P17763, CC ECO:0000305}. CC -!- FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering CC with host Dicer. {ECO:0000269|PubMed:27849599}. 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 loop. prM is the only viral peptide matured CC by host furin in the trans-Golgi network probably to avoid catastrophic CC activation of the viral fusion activity in acidic Golgi compartment CC prior to virion release. prM-E cleavage is inefficient, and many CC virions are only partially matured. These uncleaved prM would play a CC 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]: Type II fusion protein that binds to CC host cell surface receptors including LRP1, LRP4 or VLDLR and mediates CC fusion between viral and cellular membranes (PubMed:41162706). The CC envelope protein E shifts from dimeric state to trimeric state to CC perform fusion with the host membrane (By similarity). The fusion loops CC of the three subunits come together to form a membrane-insertable tip CC containing aromatic residues (By similarity). Envelope protein is CC 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 heterodimers of precursor prM and envelope protein E (By similarity). CC Envelope protein exposes a positively-charged pr-binding pocket at the CC E dimer interface, inducing (prM/E)2 dimer formation to generate smooth CC particles in the Golgi (By similarity). The virion is transported to CC the Golgi apparatus where the low pH causes dissociation of PrM-E CC heterodimers and formation of E homodimers (By similarity). prM-E CC cleavage is inefficient, and many virions are only partially matured. CC These uncleaved prM would play a role in immune evasion (By CC similarity). Pr is shed from the particle upon subsequent secretion CC into the extracellular environment, leaving an activated particle, CC prone to mediate acidic pH-triggered membrane fusion upon entry into a CC target cell (By similarity). {ECO:0000250|UniProtKB:P12823, CC ECO:0000250|UniProtKB:P14336, ECO:0000250|UniProtKB:P17763, CC ECO:0000269|PubMed:41162706}. 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, ECO:0000269|PubMed:9371625}. CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA CC replication complex that functions in virion assembly and antagonizes CC the host immune response. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the CC serine protease function of NS3. May have membrane-destabilizing CC activity and form viroporins (By similarity). CC {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}. CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities: CC serine protease, NTPase and RNA helicase. NS3 serine protease, in CC association with NS2B, performs its autocleavage and cleaves the CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B- CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and CC unwinds dsRNA in the 3' to 5' direction. Also plays a role in virus CC assembly (PubMed:18199634). {ECO:0000255|PROSITE-ProRule:PRU00860, CC ECO:0000269|PubMed:18199634}. CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy CC during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is CC required for the interferon antagonism activity of the latter. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER- CC derived membrane vesicles where the viral replication takes place. CC Inhibits interferon (IFN)-induced host STAT1 phosphorylation and CC nuclear translocation, thereby preventing the establishment of cellular CC antiviral state by blocking the IFN-alpha/beta pathway CC (PubMed:15956546). {ECO:0000250|UniProtKB:Q9Q6P4, CC ECO:0000269|PubMed:15956546}. CC -!- FUNCTION: [RNA-directed RNA polymerase/Methyltransferase NS5]: CC Replicates the viral (+) and (-) RNA genome, and performs the capping CC of genomes in the cytoplasm (PubMed:19850911). NS5 methylates viral RNA CC cap at guanine N-7 and ribose 2'-O positions (PubMed:19850911). Besides CC its 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:25211074). IFN-I induces binding CC of NS5 to host IFN-activated transcription factor STAT2, preventing its CC transcriptional activity. Host TRIM23 is the E3 ligase that interacts CC with and polyubiquitinates NS5 to promote its binding to STAT2 and CC trigger IFN-I signaling inhibition (PubMed:25211074). CC {ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:25211074}. 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:21419753}; CC -!- CATALYTIC ACTIVITY: CC Reaction=RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + CC diphosphate; Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA- CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539, CC ECO:0000269|PubMed:16051820}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- CC diphosphate + phosphate + H(+); 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 Evidence={ECO:0000269|PubMed:16051820}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); 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 + S- CC 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 + S- CC adenosyl-L-homocysteine + H(+); Xref=Rhea:RHEA:67020, Rhea:RHEA- CC COMP:17167, Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, CC ChEBI:CHEBI:167609; EC=2.1.1.57; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00924}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 9. {ECO:0000269|PubMed:21419753}; CC -!- SUBUNIT: [Capsid protein C]: Homodimer (PubMed:12768036). Interacts CC (via N-terminus) with host EXOC1 (via C-terminus); this interaction CC results in EXOC1 degradation through the proteasome degradation pathway CC (By similarity). Interacts (via the NLS) with host KPNA2/Importin CC alpha-1; this interaction allows the nuclear import of the capsid CC protein (By similarity). {ECO:0000250|UniProtKB:P17763, CC ECO:0000250|UniProtKB:Q01299, ECO:0000269|PubMed:12768036}. CC -!- SUBUNIT: [Protein prM]: Heterodimer with envelope protein E; each spike CC of the immature virion in the ER/Golgi consists of three prM-E CC heterodimers. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Small envelope protein M]: Heterotetramer with envelope CC protein E, made up of two M-E dimers; in mature virion, prefusion CC state. {ECO:0000250|UniProtKB:Q01299}. CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in mature virion, prefusion CC state (By similarity). Homotrimer; in mature virion, postfusion state CC (By similarity). Heterotetramer with the small membrane protein, made CC up of two M-E dimers; in mature virion, prefusion state (By CC similarity). Heterodimer with protein prM; each spike of the immature CC virion in the ER/Golgi consists of three prM-E heterodimers (By CC similarity). Interacts with the peptide pr; this interaction allows the CC stabilization of the E dimer at acidic pH (By similarity). Pr remains CC bound to the particle as long as the pH is acidic because of CC electrostatic complementarity, dissociation of pr occurs at neutral pH CC upon virus release from the infected cell (By similarity). Interacts CC with non-structural protein 1 (By similarity). Interacts with host CC proteins LRP1, LRP4 and VLDLR; these interactions allow viral entry CC into host cell (PubMed:41162706). {ECO:0000250|UniProtKB:P14336, CC ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:41162706}. CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when CC secreted (By similarity). Interacts with envelope protein E (By CC similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with CC serine protease NS3 (PubMed:25694595). {ECO:0000269|PubMed:25694595}. CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with CC serine protease NS3 (By similarity). May form homooligomers (By CC similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B (By CC similarity). Interacts with non-structural protein 2A (via N-terminus) CC (PubMed:25694595). 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). NS3 interacts with host PDCD6IP; this interaction CC contributes to virion release (PubMed:21044891). CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:21044891, CC ECO:0000269|PubMed:25694595}. CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease CC NS3 (By similarity). {ECO:0000250|UniProtKB:P17763}. CC -!- SUBUNIT: [RNA-directed RNA polymerase/Methyltransferase NS5]: Homodimer CC (By similarity). 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 (By similarity). CC Interacts with serine protease NS3 (By similarity). Interacts (via C- CC terminus) with host SCRIB (via PDZ3); this interaction targets NS5 to CC the cell membrane periphery and nucleus, thereby allowing efficient CC host nuclear STAT1 inhibition (By similarity). Interacts with host CC TRIM23; this interaction leads to NS5 ubiquitination (PubMed:25211074). CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:Q01299, CC ECO:0000269|PubMed:25211074}. CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion CC {ECO:0000250|UniProtKB:P17763}. Host nucleus CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm CC {ECO:0000250|UniProtKB:P17763}. Host nucleus, host nucleolus CC {ECO:0000250|UniProtKB:Q01299}. CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted CC {ECO:0000250|UniProtKB:P17763}. Note=Pr remains bound to the immature CC particle as long as the pH is acidic because of electrostatic CC complementarity, dissociation of pr occurs at neutral pH upon virus CC release from the infected cell. {ECO:0000250|UniProtKB:P14336}. CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane CC {ECO:0000269|PubMed:15507646}; Multi-pass membrane protein CC {ECO:0000269|PubMed:15507646}. Host endoplasmic reticulum membrane CC {ECO:0000269|PubMed:15507646}; Multi-pass membrane protein CC {ECO:0000255}. Note=ER membrane retention is mediated by the CC transmembrane domains. {ECO:0000269|PubMed:15507646}. CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane CC {ECO:0000305}; Multi-pass membrane protein CC {ECO:0000269|PubMed:15507646}. Host endoplasmic reticulum membrane CC {ECO:0000269|PubMed:3008425}; Multi-pass membrane protein CC {ECO:0000255}. Note=ER membrane retention is mediated by the CC transmembrane domains. {ECO:0000269|PubMed:15507646}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane; CC Peripheral membrane protein; Lumenal side CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic CC reticulum membrane; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently CC associated to serine protease subunit NS2B. {ECO:0000255|PROSITE- CC ProRule:PRU00860}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated CC vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived CC vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase/Methyltransferase CC NS5]: Host endoplasmic reticulum membrane; Peripheral membrane protein; CC Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}. CC Note=Located in RE-associated vesicles hosting the replication complex. CC NS5 protein is mainly localized in the nucleus rather than in ER CC vesicles. {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: [Protein prM]: The pr domain has a critical role in holding the CC spikes made of three prM-E heterodimers in a metastable conformation. CC {ECO:0000250|UniProtKB:P14336}. CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield CC mature proteins. The nascent capsid protein C contains a C-terminal CC hydrophobic domain that act as a signal sequence for translocation of CC prM into the lumen of the ER. Mature capsid protein C is cleaved at a CC site upstream of this hydrophobic domain by NS3. prM is cleaved in CC post-Golgi vesicles by a host furin, releasing the mature small CC envelope protein M, and peptide pr. Specific enzymatic cleavages in CC vivo yield mature proteins peptide 2K acts as a signal sequence and is CC removed from the N-terminus of NS4B by the host signal peptidase in the CC ER lumen. Signal cleavage at the 2K-4B site requires a prior NS3 CC protease-mediated cleavage at the 4A-2K site. CC {ECO:0000269|PubMed:1833562, ECO:0000269|PubMed:21419753, CC ECO:0000269|PubMed:3008425, ECO:0000269|PubMed:8116234, CC ECO:0000269|PubMed:8189517, ECO:0000269|PubMed:8421901, CC ECO:0000269|PubMed:8445732}. CC -!- PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin, CC releasing the mature small envelope protein M, and peptide pr. This CC cleavage is incomplete as up to 30% of viral particles still carry CC uncleaved prM. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: [Envelope protein E]: N-glycosylated. CC {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is CC glycosylated and this is required for efficient secretion of the CC protein from infected cells. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: [Non-structural protein 2A]: A C-terminally truncated form of non- CC structural protein 2A, NS2A-alpha, may result from partial cleavage by CC NS3. {ECO:0000269|PubMed:11967294}. CC -!- PTM: Polyubiquitinated; ubiquitination is probably mediated by host CC TRIM23 and is prerequisite for NS5-STAT2 interaction. NS5 is not CC ISGylated or sumoylated. {ECO:0000269|PubMed:25211074}. CC -!- PTM: [Serine protease NS3]: Acetylated by host KAT5. Acetylation CC modulates NS3 RNA-binding and unwinding activities and plays an CC important positive role for viral replication. CC {ECO:0000250|UniProtKB:Q32ZE1}. CC -!- PTM: [RNA-directed RNA polymerase/Methyltransferase NS5]: CC Phosphorylated on serines residues. This phosphorylation may trigger CC NS5 nuclear localization. {ECO:0000269|PubMed:9621090}. 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 --------------------------------------------------------------------------- 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; X03700; CAA27332.1; -; Genomic_RNA. DR EMBL; X15062; CAB37419.1; -; Genomic_RNA. DR EMBL; U17066; AAC54267.1; -; Genomic_RNA. DR EMBL; U17067; AAC54268.1; -; Genomic_RNA. DR EMBL; AF052437; AAC35899.1; -; Genomic_RNA. DR EMBL; AF052438; AAC35900.1; -; Genomic_RNA. DR EMBL; AF052439; AAC35901.1; -; Genomic_RNA. DR EMBL; AF052444; AAC35906.1; -; Genomic_RNA. DR EMBL; AF052445; AAC35907.1; -; Genomic_RNA. DR EMBL; AF052446; AAC35908.1; -; Genomic_RNA. DR EMBL; DQ118157; AAZ31436.1; -; Genomic_RNA. DR EMBL; DQ100292; AAZ07885.1; -; Genomic_RNA. DR PIR; A03914; GNWVY. DR PIR; S07757; GNWVYP. DR RefSeq; NP_041726.1; NC_002031.1. DR PDB; 1NA4; EM; -; -. DR PDB; 1YKS; X-ray; 1.80 A; A=1670-2107. DR PDB; 3EVA; X-ray; 1.50 A; A=2507-2772. DR PDB; 3EVB; X-ray; 1.85 A; A=2507-2772. DR PDB; 3EVC; X-ray; 1.60 A; A=2507-2772. DR PDB; 3EVD; X-ray; 1.50 A; A=2507-2772. DR PDB; 3EVE; X-ray; 1.70 A; A=2507-2772. DR PDB; 3EVF; X-ray; 1.45 A; A=2507-2772. DR PDB; 5FFM; X-ray; 2.60 A; A=1671-2107. DR PDB; 5N6B; X-ray; 1.71 A; C/F=2470-2478. DR PDB; 6EPK; X-ray; 2.70 A; B/E=122-210. DR PDB; 6IW0; X-ray; 3.60 A; A=286-680. DR PDB; 6IW1; X-ray; 3.10 A; A/B/C=286-680. DR PDB; 6IW2; X-ray; 2.90 A; A/D/G/J/M/P=286-680. DR PDB; 6IW4; X-ray; 2.80 A; A/B=286-680. DR PDB; 6QSN; X-ray; 3.00 A; A/B=2507-3411. DR PDB; 6SS7; X-ray; 2.50 A; C/F=2470-2478. DR PDB; 6SS8; X-ray; 2.24 A; C/F=2470-2478. DR PDB; 6SS9; X-ray; 2.70 A; C/F=2470-2478. DR PDB; 6SSA; X-ray; 2.11 A; C/F/I/L=2470-2478. DR PDB; 8ZB9; EM; 3.31 A; A/a=779-1130. DR PDB; 8ZBA; EM; 3.57 A; A/B/a/b=779-1130. DR PDB; 9B6U; EM; 4.00 A; A/B/C=286-676. DR PDB; 9B6X; EM; 3.60 A; A/B/C=286-676. DR PDB; 9SKO; X-ray; 1.49 A; C=2470-2479. DR PDB; 9SKP; X-ray; 1.89 A; C=2469-2478. DR AlphaFoldDB; P03314; -. DR BMRB; P03314; -. DR EMDB; EMD-39898; -. DR EMDB; EMD-39899; -. DR EMDB; EMD-44288; -. DR MDRepo; P03314; -. DR SMR; P03314; -. DR ChEMBL; CHEMBL4523585; -. DR MEROPS; S07.001; -. DR GlyCosmos; P03314; 4 sites, No reported glycans. DR iPTMnet; P03314; -. DR ABCD; P03314; 7 sequenced antibodies. DR GeneID; 1502173; -. DR KEGG; vg:1502173; -. DR BRENDA; 2.7.7.50; 6740. DR BRENDA; 3.4.21.91; 6740. DR BRENDA; 5.6.2.6; 6740. DR EvolutionaryTrace; P03314; -. DR Proteomes; UP000000360; Segment. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0030430; C:host cell cytoplasm; ISS:UniProtKB. DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; EXP:UniProtKB. DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0042025; C:host cell nucleus; ISS:UniProtKB. DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IMP:CACAO. DR GO; GO:0055036; C:virion membrane; EXP:UniProtKB. DR GO; GO:0034062; F:5'-3' RNA polymerase activity; EXP:UniProtKB. 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:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004483; F:methyltransferase cap1 activity; IEA:UniProtKB-EC. DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; EXP:UniProtKB. DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003968; F:RNA-directed 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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0039520; P:symbiont-mediated activation of host autophagy; IEA:UniProtKB-KW. DR GO; GO:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-KW. DR GO; GO:0039564; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW. DR GO; GO:0039502; P:symbiont-mediated suppression of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR CDD; cd20761; capping_2-OMTase_Flaviviridae; 1. DR CDD; cd17931; DEXHc_viral_Ns3; 1. DR CDD; cd12149; Flavi_E_C; 1. DR CDD; cd17038; Flavi_M; 1. DR CDD; cd23204; Flavivirus_RdRp; 1. DR FunFam; 1.20.1280.260:FF:000001; Envelope glycoprotein; 1. DR FunFam; 1.10.260.90:FF:000001; Genome polyprotein; 1. DR FunFam; 2.40.10.120:FF:000006; Genome polyprotein; 1. DR FunFam; 2.60.260.50:FF:000001; Genome polyprotein; 1. DR FunFam; 3.30.70.2840:FF:000001; Genome polyprotein; 1. DR FunFam; 3.30.70.2840:FF:000002; Genome polyprotein; 1. DR FunFam; 3.40.50.150:FF:000105; Genome polyprotein; 1. DR FunFam; 3.40.50.300:FF:000763; Genome polyprotein; 1. DR Gene3D; 1.10.10.930; -; 1. DR Gene3D; 1.10.260.90; -; 1. DR Gene3D; 1.20.1280.260; -; 1. DR Gene3D; 2.40.10.120; -; 2. DR Gene3D; 2.60.40.350; -; 1. DR Gene3D; 1.10.8.970; Flavivirus envelope glycoprotein M-like; 1. DR Gene3D; 2.60.260.50; Flavivirus polyprotein propeptide domain; 1. DR Gene3D; 3.30.70.2840; Flavivirus RNA-directed RNA polymerase, thumb domain; 3. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 2.60.98.10; Tick-borne Encephalitis virus Glycoprotein, domain 1; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR Gene3D; 3.30.67.10; Viral Envelope Glycoprotein, domain 2; 1. DR Gene3D; 3.30.387.10; Viral Envelope Glycoprotein, domain 3; 1. DR InterPro; IPR043502; DNA/RNA_pol_sf. DR InterPro; IPR000069; Env_glycoprot_M_flavivir. DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir. DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1. DR InterPro; IPR001122; Flavi_capsidC. DR InterPro; IPR037172; Flavi_capsidC_sf. DR InterPro; IPR011492; Flavi_DEAD. DR InterPro; IPR027287; Flavi_E_Ig-like. DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom. DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf. DR InterPro; IPR011998; Flavi_Glycoprot_E_cen/dimer. DR InterPro; IPR001157; Flavi_NS1. DR InterPro; IPR000752; Flavi_NS2A. DR InterPro; IPR000487; Flavi_NS2B. DR InterPro; IPR001850; Flavi_NS3_S7. DR InterPro; IPR000404; Flavi_NS4A. DR InterPro; IPR001528; Flavi_NS4B. DR InterPro; IPR046811; Flavi_NS5_thumb. DR InterPro; IPR002535; Flavi_propep. DR InterPro; IPR038688; Flavi_propep_sf. DR InterPro; IPR047530; Flavi_RdRp. DR InterPro; IPR000208; Flavi_RdRp_fingers/palm. DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf. DR InterPro; IPR014412; Gen_Poly_FLV. DR InterPro; IPR036253; Glycoprot_cen/dimer_sf. DR InterPro; IPR038055; Glycoprot_E_dimer_dom. DR InterPro; IPR013756; GlyE_cen_dom_subdom2. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C-like. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase. DR InterPro; IPR049486; NS3-hel_C_flaviviridae. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR NCBIfam; TIGR04240; flavi_E_stem; 1. DR Pfam; PF20907; Flav_NS3-hel_C; 1. DR Pfam; PF01003; Flavi_capsid; 1. DR Pfam; PF07652; Flavi_DEAD; 1. DR Pfam; PF21659; Flavi_E_stem; 1. DR Pfam; PF02832; Flavi_glycop_C; 1. DR Pfam; PF00869; Flavi_glycoprot; 1. DR Pfam; PF01004; Flavi_M; 1. DR Pfam; PF00948; Flavi_NS1; 1. DR Pfam; PF01005; Flavi_NS2A; 1. DR Pfam; PF01002; Flavi_NS2B; 1. DR Pfam; PF01350; Flavi_NS4A; 1. DR Pfam; PF01349; Flavi_NS4B; 1. DR Pfam; PF00972; Flavi_NS5; 1. DR Pfam; PF20483; Flavi_NS5_thumb; 1. DR Pfam; PF01570; Flavi_propep; 1. DR Pfam; PF01728; FtsJ; 1. DR Pfam; PF00949; Peptidase_S7; 1. DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF56672; DNA/RNA polymerases; 1. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR SUPFAM; SSF56983; Viral glycoprotein, central and dimerisation domains; 1. DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1. DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activation of host autophagy by virus; KW ATP-binding; Capsid protein; KW Clathrin-mediated endocytosis of virus by host; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disulfide bond; Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; GTP-binding; KW Helicase; Host cytoplasm; Host endoplasmic reticulum; Host membrane; KW 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 STAT2 by virus; Interferon antiviral system evasion; KW Isopeptide bond; Membrane; Metal-binding; Methyltransferase; mRNA capping; KW 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 Ubl conjugation; Viral attachment to host cell; Viral envelope protein; KW Viral immunoevasion; Viral penetration into host cytoplasm; KW Viral RNA replication; Virion; Virus endocytosis by host; KW Virus entry into host cell; Zinc. FT CHAIN 1..3411 FT /note="Genome polyprotein" FT /id="PRO_0000405153" FT CHAIN 1..101 FT /note="Capsid protein C" FT /evidence="ECO:0000269|PubMed:8189517" FT /id="PRO_0000037754" FT PROPEP 102..121 FT /note="ER anchor for the capsid protein C, removed in FT mature form by serine protease NS3" FT /evidence="ECO:0000269|PubMed:8189517" FT /id="PRO_0000261384" FT CHAIN 122..285 FT /note="Protein prM" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000261385" FT CHAIN 122..210 FT /note="Peptide pr" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037755" FT CHAIN 211..285 FT /note="Small envelope protein M" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037756" FT CHAIN 286..778 FT /note="Envelope protein E" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037757" FT CHAIN 779..1130 FT /note="Non-structural protein 1" FT /evidence="ECO:0000269|PubMed:3008425" FT /id="PRO_0000037758" FT CHAIN 1131..1354 FT /note="Non-structural protein 2A" FT /evidence="ECO:0000250|UniProtKB:P29990" FT /id="PRO_0000037759" FT CHAIN 1355..1484 FT /note="Serine protease subunit NS2B" FT /evidence="ECO:0000269|PubMed:3008425" FT /id="PRO_0000037760" FT CHAIN 1485..2107 FT /note="Serine protease NS3" FT /evidence="ECO:0000269|PubMed:1833562, FT ECO:0000269|PubMed:8421901" FT /id="PRO_0000037761" FT CHAIN 2108..2233 FT /note="Non-structural protein 4A" FT /evidence="ECO:0000269|PubMed:8445732" FT /id="PRO_0000037762" FT PEPTIDE 2234..2256 FT /note="Peptide 2k" FT /evidence="ECO:0000269|PubMed:2922923" FT /id="PRO_0000261387" FT CHAIN 2257..2506 FT /note="Non-structural protein 4B" FT /evidence="ECO:0000269|PubMed:8421901" FT /id="PRO_0000037763" FT CHAIN 2507..3411 FT /note="RNA-directed RNA polymerase/Methyltransferase NS5" FT /evidence="ECO:0000269|PubMed:1833562, FT ECO:0000269|PubMed:3008425" FT /id="PRO_0000037764" FT TOPO_DOM 1..104 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 105..125 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 126..244 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 245..265 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 266..270 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 271..285 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 286..730 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 731..751 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 752..757 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 758..778 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 779..1132 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1133..1153 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1154..1201 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1202..1222 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1223..1287 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1288..1308 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1309..1355 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1356..1376 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1377..1378 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1379..1399 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1400..1456 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 1457..1477 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1478..2157 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2158..2178 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2179..2186 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2187..2207 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2208..2209 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2210..2230 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2231..2241 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2242..2262 FT /note="Helical; Note=Signal for NS4B" FT /evidence="ECO:0000255" FT TOPO_DOM 2263..2293 FT /note="Lumenal" FT /evidence="ECO:0000255" FT INTRAMEM 2294..2314 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2315..2360 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2361..2381 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2382..2421 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2422..2442 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2443..2445 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2446..2466 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2467..3411 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 1485..1665 FT /note="Peptidase S7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860" FT DOMAIN 1669..1825 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 1820..1997 FT /note="Helicase C-terminal" FT DOMAIN 2507..2771 FT /note="mRNA cap 0-1 NS5-type MT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT DOMAIN 3035..3187 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT REGION 38..72 FT /note="Hydrophobic; homodimerization of capsid protein C" FT /evidence="ECO:0000250|UniProtKB:P29990" FT REGION 383..396 FT /note="Fusion peptide loop" FT /evidence="ECO:0000250|UniProtKB:P14336" FT REGION 1407..1446 FT /note="Interacts with and activates NS3 protease" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859" FT REGION 1673..1676 FT /note="Important for RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P14340" FT REGION 2724..2728 FT /note="Interaction with host SCRIB" FT /evidence="ECO:0000250|UniProtKB:Q01299" FT MOTIF 83..101 FT /note="Bipartite nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:P14336" FT MOTIF 1773..1776 FT /note="DEAH box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOTIF 2878..2911 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250" FT ACT_SITE 1537 FT /note="Charge relay system; for serine protease NS3 FT activity" FT ACT_SITE 1561 FT /note="Charge relay system; for serine protease NS3 FT activity" FT ACT_SITE 1622 FT /note="Charge relay system; for serine protease NS3 FT activity" FT ACT_SITE 2567 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2652 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2688 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT ACT_SITE 2724 FT /note="For 2'-O-MTase activity" FT /evidence="ECO:0000250|UniProtKB:Q6YMS4" FT BINDING 1682..1689 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 2562 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2592 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2593 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2610 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2611 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2637 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2638 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2653 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2726 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT BINDING 2945 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 2949 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 2954 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 2957 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 3222 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 3238 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P14335" FT BINDING 3357 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 81 FT /note="Homodimerization of capsid protein" FT /evidence="ECO:0000250|UniProtKB:P12823" FT SITE 95 FT /note="Homodimerization of capsid protein" FT /evidence="ECO:0000250|UniProtKB:P12823" FT SITE 101..102 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:8189517" FT SITE 121..122 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000269|PubMed:8189517" FT SITE 210..211 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 285..286 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 778..779 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000269|PubMed:3008425" FT SITE 1130..1131 FT /note="Cleavage; by host" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 1320..1321 FT /note="Possible cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:8806496" FT SITE 1354..1355 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:21419753, FT ECO:0000269|PubMed:8116234" FT SITE 1484..1485 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:21419753, FT ECO:0000269|PubMed:3008425" FT SITE 1945 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 1948 FT /note="Involved in NS3 ATPase and RTPase activities" FT /evidence="ECO:0000250|UniProtKB:P14335" FT SITE 2107..2108 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:21419753, FT ECO:0000269|PubMed:8421901, ECO:0000269|PubMed:8445732" FT SITE 2233..2234 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:8445732" FT SITE 2256..2257 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P29990" FT SITE 2506..2507 FT /note="Cleavage; by viral protease NS3" FT /evidence="ECO:0000269|PubMed:3008425, FT ECO:0000269|PubMed:8421901, ECO:0000269|PubMed:8445732" FT SITE 2519 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2522 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2523 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2525 FT /note="mRNA cap binding; via carbonyl oxygen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2530 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2534 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2567 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2652 FT /note="Essential for 2'-O-methyltransferase and N-7 FT methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:18757072" FT SITE 2656 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2688 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT SITE 2719 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2721 FT /note="mRNA cap binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924, FT ECO:0000269|PubMed:19101564" FT SITE 2724 FT /note="Essential for 2'-O-methyltransferase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924" FT MOD_RES 1877 FT /note="N6-acetyllysine; by host" FT /evidence="ECO:0000250|UniProtKB:Q32ZE1" FT MOD_RES 2562 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18757072" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 150 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 908 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 986 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT DISULFID 151..186 FT /evidence="ECO:0000250|UniProtKB:P14336" FT DISULFID 162..199 FT /evidence="ECO:0000250|UniProtKB:P14336" FT DISULFID 170..184 FT /evidence="ECO:0000250|UniProtKB:P14336" FT DISULFID 288..315 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 345..401 FT /evidence="ECO:0000250|UniProtKB:P06935" FT DISULFID 359..390 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 377..406 FT /evidence="ECO:0000250|UniProtKB:P06935" FT DISULFID 467..568 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 585..615 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 782..793 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 833..921 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 957..1002 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1058..1107 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1069..1090 FT /evidence="ECO:0000250|UniProtKB:P17763" FT DISULFID 1091..1094 FT /evidence="ECO:0000250|UniProtKB:P17763" FT VARIANT 341 FT /note="V -> A (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 438 FT /note="N -> T (in strain: Isolate 17D-204-USAHONG1 vaccine, FT Isolate 17D-204-USAHONG2 vaccine and Isolate FT 17D-204-USAHONG3 vaccine)" FT VARIANT 440 FT /note="D -> S (in strain: Isolate 17DD vaccine)" FT VARIANT 610 FT /note="S -> P (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 629 FT /note="I -> V (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT VARIANT 701 FT /note="T -> V (in strain: Isolate 17DD vaccine)" FT VARIANT 744 FT /note="A -> V (in strain: Isolate 17D-204-South Africa FT vaccine large plaque variant)" FT VARIANT 764 FT /note="L -> M (in strain: Isolate 17D-204-South Africa FT vaccine large plaque variant)" FT VARIANT 1299 FT /note="F -> L (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 1666 FT /note="Q -> R (in strain: Isolate 17DD vaccine)" FT VARIANT 1669 FT /note="P -> S (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT VARIANT 1679 FT /note="V -> I (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 2214 FT /note="V -> I (in strain: Isolate 17D-204-USAHONG1 vaccine, FT Isolate 17D-204-USAHONG2 vaccine, Isolate 17D-204-USAHONG3 FT vaccine, Isolate Spain/AVD2791-93F/04 vaccine, Isolate FT Brazil/YF-VAVD/75 vaccine, Isolate 17DD vaccine and Isolate FT Pasteur 17D-204 vaccine)" FT VARIANT 2277 FT /note="P -> S (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT VARIANT 2401 FT /note="E -> K (in strain: Isolate 17D-204-South Africa FT vaccine large plaque variant, Isolate 17D-204-South Africa FT vaccine medium plaque variant, Isolate 17D-204-South Africa FT vaccine, Isolate 17D-204-USAHONG1 vaccine, Isolate FT 17D-204-USAHONG2 vaccine, Isolate 17D-204-USAHONG3 vaccine, FT Isolate Brazil/YF-VAVD/75 vaccine, Isolate FT Spain/AVD2791-93F/04 vaccine, Isolate 17DD vaccine and FT Isolate Pasteur 17D-204 vaccine)" FT VARIANT 2460 FT /note="L -> S (in strain: Isolate 17D-204-USAHONG vaccine1, FT Isolate 17D-204-USAHONG2 vaccine and Isolate FT 17D-204-USAHONG3 vaccine)" FT VARIANT 2528 FT /note="R -> Q (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 2643 FT /note="P -> S (in strain: Isolate 17D-204-South Africa FT vaccine medium plaque variant)" FT VARIANT 2661 FT /note="V -> I (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT VARIANT 2897 FT /note="N -> S (in strain: Isolate Brazil/YF-VAVD/75 vaccine FT and Isolate 17DD vaccine)" FT VARIANT 3110 FT /note="G -> R (in strain: Isolate 17D-204-USAHONG2 FT vaccine)" FT VARIANT 3135 FT /note="M -> N (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT VARIANT 3163 FT /note="D -> N (in strain: Isolate 17D-204-South Africa FT vaccine large plaque variant, Isolate 17D-204-South Africa FT vaccine medium plaque variant, Isolate 17D-204-South Africa FT vaccine, Isolate 17D-204-USAHONG1 vaccine, Isolate FT 17D-204-USAHONG2 vaccine, Isolate 17D-204-USAHONG3 vaccine, FT Isolate Brazil/YF-VAVD/75 vaccine, Isolate FT Spain/AVD2791-93F/04 vaccine, Isolate 17DD vaccine and FT Isolate Pasteur 17D-204 vaccine)" FT VARIANT 3222 FT /note="H -> R (in strain: Isolate Brazil/YF-VAVD/75 FT vaccine)" FT MUTAGEN 98..101 FT /note="RKRR->AAAA: Complete loss of NS2B-NS3 cleavage." FT MUTAGEN 98..101 FT /note="RKRR->AKAA: Complete loss of NS2B-NS3 cleavage." FT MUTAGEN 98..101 FT /note="RKRR->AKRA: Reduces NS2B-NS3 cleavage efficiency." FT MUTAGEN 98..100 FT /note="RKR->AAA: Complete loss of NS2B-NS3 cleavage." FT MUTAGEN 98..100 FT /note="RKR->AKA: Complete loss of NS2B-NS3 cleavage." FT MUTAGEN 98..99 FT /note="RK->AA: Reduces NS2B-NS3 cleavage efficiency." FT MUTAGEN 99..101 FT /note="KRR->ARA: Complete loss of NS2B-NS3 cleavage." FT /evidence="ECO:0000269|PubMed:10482557" FT MUTAGEN 99..100 FT /note="KR->AA: Complete loss of NS2B-NS3 cleavage." FT MUTAGEN 100..101 FT /note="RR->AA: Reduces NS2B-NS3 cleavage efficiency." FT MUTAGEN 116..121 FT /note="LLMTGG->VPQAQA: Complete loss of infectious virus FT production. Enhances signal peptidase cleavage in vitro of FT nascent capsid protein C." FT /evidence="ECO:0000269|PubMed:10590087" FT MUTAGEN 908 FT /note="N->A: Reduces viral RNA accumulation and NS1 FT secretion." FT /evidence="ECO:0000269|PubMed:8806496" FT MUTAGEN 910 FT /note="S->A: Reduces viral RNA accumulation and NS1 FT secretion." FT /evidence="ECO:0000269|PubMed:8806496" FT MUTAGEN 986 FT /note="N->A: No effect." FT /evidence="ECO:0000269|PubMed:8806496" FT MUTAGEN 988 FT /note="T->A: No effect." FT /evidence="ECO:0000269|PubMed:8806496" FT MUTAGEN 1077 FT /note="R->A: Blocks RNA replication." FT /evidence="ECO:0000269|PubMed:8985349" FT MUTAGEN 1152..1154 FT /note="RKR->AAA: Defective in infectious particle FT production; almost no effect on viral replication." FT /evidence="ECO:0000269|PubMed:25694595" FT MUTAGEN 1229..1231 FT /note="RER->AAA: Defective in infectious particle FT production; almost no effect on viral replication." FT /evidence="ECO:0000269|PubMed:25694595" FT MUTAGEN 1319..1321 FT /note="QKT->RRS: Increases NS2A-alpha processing, complete FT loss of NS2A." FT /evidence="ECO:0000269|PubMed:11967294" FT MUTAGEN 1319 FT /note="Q->A: Almost no effect on viral replication." FT /evidence="ECO:0000269|PubMed:25694595" FT MUTAGEN 1319 FT /note="Q->S: Complete loss of cleavage and NS2A alpha. FT Complete loss of infectivity." FT /evidence="ECO:0000269|PubMed:11967294" FT MUTAGEN 1320 FT /note="K->E,I,Q,S: Complete loss of cleavage and NS2A-alpha FT processing. Complete loss of infectivity." FT /evidence="ECO:0000269|PubMed:11967294" FT MUTAGEN 1320 FT /note="K->R: No effect on NS2A-alpha processing." FT /evidence="ECO:0000269|PubMed:11967294" FT MUTAGEN 1321 FT /note="T->V: Complete loss of cleavage and NS2A alpha FT synthesis. Complete loss of infectivity." FT /evidence="ECO:0000269|PubMed:11967294" FT MUTAGEN 1351 FT /note="F->C,I,V: Enhances NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1351 FT /note="F->G: No effect on NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1352 FT /note="G->A,K: Enhances NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1352 FT /note="G->E,V: Reduces NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1353 FT /note="R->H,K,R,T: Reduces NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1353 FT /note="R->L,P: Complete loss of NS2A-NS2B cleavage." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1354 FT /note="R->I,N,S,T: Complete loss of NS2A-NS2B cleavage." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1354 FT /note="R->K: Reduces of NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1355 FT /note="S->D,K,R,V: Complete loss of NS2A-NS2B cleavage." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1355 FT /note="S->G: Reduces of NS2A-NS2B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8116234" FT MUTAGEN 1406..1409 FT /note="ELKK->ALAA: Complete loss of polyprotein cleavage." FT /evidence="ECO:0000269|PubMed:10998334" FT MUTAGEN 1537 FT /note="H->A: Complete loss NS3 protease activity." FT /evidence="ECO:0000269|PubMed:2147282" FT MUTAGEN 1561 FT /note="D->A,N: Complete loss NS3 protease activity." FT /evidence="ECO:0000269|PubMed:2147282" FT MUTAGEN 1622 FT /note="S->A: Complete loss NS3 protease activity." FT /evidence="ECO:0000269|PubMed:2147282" FT MUTAGEN 1622 FT /note="S->C: Diminishes NS3 protease activity." FT /evidence="ECO:0000269|PubMed:2147282" FT MUTAGEN 1833 FT /note="W->A: Complete loss of production of infectious FT virus particles." FT /evidence="ECO:0000269|PubMed:18199634" FT MUTAGEN 2107 FT /note="R->A,L,M,T,V: Reduces NS4A-NS4B cleavage FT efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2107 FT /note="R->E: Complete loss of NS4A-NS4B cleavage." FT /evidence="ECO:0000269|PubMed:8421901, FT ECO:0000269|PubMed:8445732" FT MUTAGEN 2107 FT /note="R->K: No effect on NS4A-NS4B cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2107 FT /note="R->P: Complete loss of NS4A-NS4B cleavage." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2234 FT /note="S->A,T: No effect on NS4A-NS4B cleavage." FT /evidence="ECO:0000269|PubMed:8445732" FT MUTAGEN 2234 FT /note="S->I,P: No effect on NS4A-NS4B cleavage." FT /evidence="ECO:0000269|PubMed:8445732" FT MUTAGEN 2505 FT /note="R->A,I,L,Q,S,T: No effect on NS4B-NS5 cleavage FT efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2505 FT /note="R->P: Reduces NS4B-NS5 cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2506 FT /note="R->E: Complete loss of NS4B-NS5 cleavage." FT /evidence="ECO:0000269|PubMed:8421901, FT ECO:0000269|PubMed:8445732" FT MUTAGEN 2506 FT /note="R->H,N,Q: Reduces NS4B-NS5 cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2506 FT /note="R->K: No effect on NS4B-NS5 cleavage efficiency." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2506 FT /note="R->Y: Complete loss of NS4B-NS5 cleavage." FT /evidence="ECO:0000269|PubMed:8421901" FT MUTAGEN 2507 FT /note="G->A,S: Reduces NS4B-NS5 cleavage efficiency." FT MUTAGEN 2507 FT /note="G->E,K,L,M,N,V: Reduces NS4B-NS5 cleavage FT efficiency." FT MUTAGEN 2512 FT /note="K->R: Complete loss of NS5 binding to STAT2 after FT IFN-I stimulation." FT /evidence="ECO:0000269|PubMed:25211074" FT MUTAGEN 2562 FT /note="S->A: Complete loss of 2'-O-MTase activity." FT /evidence="ECO:0000269|PubMed:18757072" FT STRAND 123..127 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 130..134 FT /evidence="ECO:0007829|PDB:6EPK" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 143..146 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 149..153 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 160..169 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 183..188 FT /evidence="ECO:0007829|PDB:6EPK" FT STRAND 191..199 FT /evidence="ECO:0007829|PDB:6EPK" FT TURN 288..290 FT /evidence="ECO:0007829|PDB:6IW2" FT STRAND 292..298 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 305..311 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 315..319 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 326..335 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 340..357 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 370..385 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 386..388 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 394..414 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 417..419 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 421..428 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 434..439 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 442..446 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 453..457 FT /evidence="ECO:0007829|PDB:6IW4" FT TURN 458..460 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 461..465 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:6IW4" FT TURN 473..475 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 479..483 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 486..490 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 492..496 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 505..507 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 513..516 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 517..519 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 529..531 FT /evidence="ECO:0007829|PDB:6IW4" FT HELIX 536..542 FT /evidence="ECO:0007829|PDB:6IW4" FT TURN 543..545 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 548..551 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 559..562 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 565..571 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 582..584 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 589..597 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 599..601 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 603..611 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 613..616 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 619..626 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 633..636 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 640..643 FT /evidence="ECO:0007829|PDB:6IW1" FT STRAND 646..653 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 656..666 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 670..676 FT /evidence="ECO:0007829|PDB:6IW4" FT STRAND 782..785 FT /evidence="ECO:0007829|PDB:8ZB9" FT TURN 786..789 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 790..793 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 796..800 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 801..804 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 819..829 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 840..859 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 863..867 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 881..884 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 909..914 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 919..921 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 923..925 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 931..933 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 946..949 FT /evidence="ECO:0007829|PDB:8ZB9" FT HELIX 959..961 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 963..967 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 970..975 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 978..984 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 986..996 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1048..1056 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1063..1065 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1067..1069 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1077..1079 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1089..1093 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1099..1102 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1104..1108 FT /evidence="ECO:0007829|PDB:8ZB9" FT STRAND 1677..1680 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1688..1692 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1693..1702 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1707..1713 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1714..1723 FT /evidence="ECO:0007829|PDB:1YKS" FT TURN 1724..1726 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1729..1734 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1746..1750 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1751..1758 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1760..1762 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1768..1772 FT /evidence="ECO:0007829|PDB:1YKS" FT TURN 1773..1776 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1780..1794 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1799..1803 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1821..1825 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1834..1836 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1838..1842 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1847..1850 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1854..1866 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1871..1873 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1876..1878 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1892..1899 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1909..1913 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1916..1923 FT /evidence="ECO:0007829|PDB:1YKS" FT TURN 1924..1927 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1928..1936 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1939..1946 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 1958..1962 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1974..1983 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 1989..1991 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2000..2003 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 2004..2006 FT /evidence="ECO:0007829|PDB:1YKS" FT TURN 2008..2011 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2015..2026 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2032..2040 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2049..2051 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2056..2058 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 2063..2065 FT /evidence="ECO:0007829|PDB:5FFM" FT STRAND 2069..2071 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 2077..2079 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 2083..2086 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2087..2089 FT /evidence="ECO:0007829|PDB:1YKS" FT STRAND 2090..2092 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2093..2103 FT /evidence="ECO:0007829|PDB:1YKS" FT TURN 2104..2106 FT /evidence="ECO:0007829|PDB:1YKS" FT HELIX 2514..2524 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2527..2534 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2536..2541 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2544..2551 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2564..2573 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2581..2586 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2592..2598 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2603..2609 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2616..2620 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2627..2629 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2630..2633 FT /evidence="ECO:0007829|PDB:3EVF" FT TURN 2638..2640 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2647..2651 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2660..2678 FT /evidence="ECO:0007829|PDB:3EVF" FT TURN 2679..2681 FT /evidence="ECO:0007829|PDB:3EVD" FT STRAND 2683..2690 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2695..2708 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2711..2713 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2725..2730 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2735..2751 FT /evidence="ECO:0007829|PDB:3EVF" FT STRAND 2757..2760 FT /evidence="ECO:0007829|PDB:3EVF" FT HELIX 2781..2794 FT /evidence="ECO:0007829|PDB:6QSN" FT TURN 2795..2798 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 2808..2819 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2830..2835 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2837..2839 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2843..2846 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 2848..2850 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2855..2861 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2862..2866 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2870..2874 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2875..2892 FT /evidence="ECO:0007829|PDB:6QSN" FT TURN 2893..2895 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2903..2909 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2929..2932 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2936..2950 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 2959..2963 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 2967..2969 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 2980..2983 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2986..2996 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 2998..3001 FT /evidence="ECO:0007829|PDB:6QSN" FT TURN 3002..3005 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3007..3010 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3011..3013 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3019..3031 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3045..3048 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3051..3057 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3058..3063 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3066..3074 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3075..3081 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3085..3090 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3095..3102 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3113..3133 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3139..3141 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3147..3166 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3168..3171 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3174..3177 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3182..3186 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3189..3193 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3210..3212 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3213..3215 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3221..3227 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3233..3238 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3241..3248 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3253..3255 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3258..3275 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3280..3292 FT /evidence="ECO:0007829|PDB:6QSN" FT STRAND 3314..3317 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3319..3324 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3325..3329 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3343..3345 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3351..3356 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3364..3384 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3392..3395 FT /evidence="ECO:0007829|PDB:6QSN" FT HELIX 3397..3399 FT /evidence="ECO:0007829|PDB:6QSN" SQ SEQUENCE 3411 AA; 379518 MW; 680E0FACD23DCFA6 CRC64; MSGRKAQGKT LGVNMVRRGV RSLSNKIKQK TKQIGNRPGP SRGVQGFIFF FLFNILTGKK ITAHLKRLWK MLDPRQGLAV LRKVKRVVAS LMRGLSSRKR RSHDVLTVQF LILGMLLMTG GVTLVRKNRW LLLNVTSEDL GKTFSVGTGN CTTNILEAKY WCPDSMEYNC PNLSPREEPD DIDCWCYGVE NVRVAYGKCD SAGRSRRSRR AIDLPTHENH GLKTRQEKWM TGRMGERQLQ KIERWFVRNP FFAVTALTIA YLVGSNMTQR VVIALLVLAV GPAYSAHCIG ITDRDFIEGV HGGTWVSATL EQDKCVTVMA PDKPSLDISL ETVAIDRPAE VRKVCYNAVL THVKINDKCP STGEAHLAEE NEGDNACKRT YSDRGWGNGC GLFGKGSIVA CAKFTCAKSM SLFEVDQTKI QYVIRAQLHV GAKQENWNTD IKTLKFDALS GSQEVEFIGY GKATLECQVQ TAVDFGNSYI AEMETESWIV DRQWAQDLTL PWQSGSGGVW REMHHLVEFE PPHAATIRVL ALGNQEGSLK TALTGAMRVT KDTNDNNLYK LHGGHVSCRV KLSALTLKGT SYKICTDKMF FVKNPTDTGH GTVVMQVKVS KGAPCRIPVI VADDLTAAIN KGILVTVNPI ASTNDDEVLI EVNPPFGDSY IIVGRGDSRL TYQWHKEGSS IGKLFTQTMK GVERLAVMGD TAWDFSSAGG FFTSVGKGIH TVFGSAFQGL FGGLNWITKV IMGAVLIWVG INTRNMTMSM SMILVGVIMM FLSLGVGADQ GCAINFGKRE LKCGDGIFIF RDSDDWLNKY SYYPEDPVKL ASIVKASFEE GKCGLNSVDS LEHEMWRSRA DEINAIFEEN EVDISVVVQD PKNVYQRGTH PFSRIRDGLQ YGWKTWGKNL VFSPGRKNGS FIIDGKSRKE CPFSNRVWNS FQIEEFGTGV FTTRVYMDAV FEYTIDCDGS ILGAAVNGKK SAHGSPTFWM GSHEVNGTWM IHTLEALDYK ECEWPLTHTI GTSVEESEMF MPRSIGGPVS SHNHIPGYKV QTNGPWMQVP LEVKREACPG TSVIIDGNCD GRGKSTRSTT DSGKVIPEWC CRSCTMPPVS FHGSDGCWYP MEIRPRKTHE SHLVRSWVTA GEIHAVPFGL VSMMIAMEVV LRKRQGPKQM LVGGVVLLGA MLVGQVTLLD LLKLTVAVGL HFHEMNNGGD AMYMALIAAF SIRPGLLIGF GLRTLWSPRE RLVLTLGAAM VEIALGGVMG GLWKYLNAVS LCILTINAVA SRKASNTILP LMALLTPVTM AEVRLAAMFF CAVVIIGVLH QNFKDTSMQK TIPLVALTLT SYLGLTQPFL GLCAFLATRI FGRRSIPVNE ALAAAGLVGV LAGLAFQEME NFLGPIAVGG LLMMLVSVAG RVDGLELKKL GEVSWEEEAE ISGSSARYDV ALSEQGEFKL LSEEKVPWDQ VVMTSLALVG AALHPFALLL VLAGWLFHVR GARRSGDVLW DIPTPKIIEE CEHLEDGIYG IFQSTFLGAS QRGVGVAQGG VFHTMWHVTR GAFLVRNGKK LIPSWASVKE DLVAYGGSWK LEGRWDGEEE VQLIAAVPGK NVVNVQTKPS LFKVRNGGEI GAVALDYPSG TSGSPIVNRN GEVIGLYGNG ILVGDNSFVS AISQTEVKEE GKEELQEIPT MLKKGMTTVL DFHPGAGKTR RFLPQILAEC ARRRLRTLVL APTRVVLSEM KEAFHGLDVK FHTQAFSAHG SGREVIDAMC HATLTYRMLE PTRVVNWEVI IMDEAHFLDP ASIAARGWAA HRARANESAT ILMTATPPGT SDEFPHSNGE IEDVQTDIPS EPWNTGHDWI LADKRPTAWF LPSIRAANVM AASLRKAGKS VVVLNRKTFE REYPTIKQKK PDFILATDIA EMGANLCVER VLDCRTAFKP VLVDEGRKVA IKGPLRISAS SAAQRRGRIG RNPNRDGDSY YYSEPTSENN AHHVCWLEAS MLLDNMEVRG GMVAPLYGVE GTKTPVSPGE MRLRDDQRKV FRELVRNCDL PVWLSWQVAK AGLKTNDRKW CFEGPEEHEI LNDSGETVKC RAPGGAKKPL RPRWCDERVS SDQSALSEFI KFAEGRRGAA EVLVVLSELP DFLAKKGGEA MDTISVFLHS EEGSRAYRNA LSMMPEAMTI VMLFILAGLL TSGMVIFFMS PKGISRMSMA MGTMAGCGYL MFLGGVKPTH ISYVMLIFFV LMVVVIPEPG QQRSIQDNQV AYLIIGILTL VSAVAANELG MLEKTKEDLF GKKNLIPSSA SPWSWPDLDL KPGAAWTVYV GIVTMLSPML HHWIKVEYGN LSLSGIAQSA SVLSFMDKGI PFMKMNISVI MLLVSGWNSI TVMPLLCGIG CAMLHWSLIL PGIKAQQSKL AQRRVFHGVA ENPVVDGNPT VDIEEAPEMP ALYEKKLALY LLLALSLASV AMCRTPFSLA EGIVLASAAL GPLIEGNTSL LWNGPMAVSM TGVMRGNHYA FVGVMYNLWK MKTGRRGSAN GKTLGEVWKR ELNLLDKRQF ELYKRTDIVE VDRDTARRHL AEGKVDTGVA VSRGTAKLRW FHERGYVKLE GRVIDLGCGR GGWCYYAAAQ KEVSGVKGFT LGRDGHEKPM NVQSLGWNII TFKDKTDIHR LEPVKCDTLL CDIGESSSSS VTEGERTVRV LDTVEKWLAC GVDNFCVKVL APYMPDVLEK LELLQRRFGG TVIRNPLSRN STHEMYYVSG ARSNVTFTVN QTSRLLMRRM RRPTGKVTLE ADVILPIGTR SVETDKGPLD KEAIEERVER IKSEYMTSWF YDNDNPYRTW HYCGSYVTKT SGSAASMVNG VIKILTYPWD RIEEVTRMAM TDTTPFGQQR VFKEKVDTRA KDPPAGTRKI MKVVNRWLFR HLAREKNPRL CTKEEFIAKV RSHAAIGAYL EEQEQWKTAN EAVQDPKFWE LVDEERKLHQ QGRCRTCVYN MMGKREKKLS EFGKAKGSRA IWYMWLGARY LEFEALGFLN EDHWASRENS GGGVEGIGLQ YLGYVIRDLA AMDGGGFYAD DTAGWDTRIT EADLDDEQEI LNYMSPHHKK LAQAVMEMTY KNKVVKVLRP APGGKAYMDV ISRRDQRGSG QVVTYALNTI TNLKVQLIRM AEAEMVIHHQ HVQDCDESVL TRLEAWLTEH GCDRLKRMAV SGDDCVVRPI DDRFGLALSH LNAMSKVRKD ISEWQPSKGW NDWENVPFCS HHFHELQLKD GRRIVVPCRE QDELIGRGRV SPGNGWMIKE TACLSKAYAN MWSLMYFHKR DMRLLSLAVS SAVPTSWVPQ GRTTWSIHGK GEWMTTEDML EVWNRVWITN NPHMQDKTMV KKWRDVPYLT KRQDKLCGSL IGMTNRATWA SHIHLVIHRI RTLIGQEKYT DYLTVMDRYS VDADLQLGEL I //