ID POLG_DEN27 Reviewed; 3391 AA. AC P29991; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 25-APR-2018, entry version 160. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Capsid protein C; DE AltName: Full=Core protein; DE Contains: DE RecName: Full=Protein prM; DE Contains: DE RecName: Full=Peptide pr; DE Contains: DE RecName: Full=Small envelope protein M; DE AltName: Full=Matrix protein; DE Contains: DE RecName: Full=Envelope protein E; DE Contains: DE RecName: Full=Non-structural protein 1; DE Short=NS1; DE Contains: DE RecName: Full=Non-structural protein 2A; DE Short=NS2A; DE Contains: DE RecName: Full=Serine protease subunit NS2B; DE AltName: Full=Flavivirin protease NS2B regulatory subunit; DE AltName: Full=Non-structural protein 2B; DE Contains: DE RecName: Full=Serine protease NS3; DE EC=3.4.21.91; DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Q6P4}; DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9Q6P4}; DE AltName: Full=Flavivirin protease NS3 catalytic subunit; DE AltName: Full=Non-structural protein 3; DE Contains: DE RecName: Full=Non-structural protein 4A; DE Short=NS4A; DE Contains: DE RecName: Full=Peptide 2k; DE Contains: DE RecName: Full=Non-structural protein 4B; DE Short=NS4B; DE Contains: DE RecName: Full=RNA-directed RNA polymerase NS5; DE EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924}; DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924}; DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539}; DE AltName: Full=Non-structural protein 5; OS Dengue virus type 2 (strain 16681-PDK53) (DENV-2). OC Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; OC Flaviviridae; Flavivirus; Dengue virus group. OX NCBI_TaxID=31635; OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti). OH NCBI_TaxID=299627; Aedes furcifer (Mosquito). OH NCBI_TaxID=299628; Aedes taylori (Mosquito). OH NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas). OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=1312269; DOI=10.1016/0042-6822(92)90460-7; RA Blok J., McWilliam S.M., Butler H.C., Gibbs A.J., Weiller G., RA Herring B.L., Hemsley A.C., Aaskov J.G., Yoksan S., Bhamarapravati N.; RT "Comparison of a dengue-2 virus and its candidate vaccine derivative: RT sequence relationships with the flaviviruses and other viruses."; RL Virology 187:573-590(1992). RN [2] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 578-674. RX PubMed=18264114; DOI=10.1038/nsmb.1382; RA Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., RA Battisti A.J., Sukupolvi-Petty S., Sedlak D., Fremont D.H., RA Chipman P.R., Roehrig J.T., Diamond M.S., Kuhn R.J., Rossmann M.G.; RT "Binding of a neutralizing antibody to dengue virus alters the RT arrangement of surface glycoproteins."; RL Nat. Struct. Mol. Biol. 15:312-317(2008). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2493-2757. 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., RA Keenan S.M., Peersen O.B.; RT "Analysis of flavivirus NS5 methyltransferase cap binding."; RL J. Mol. Biol. 385:1643-1654(2009). RN [4] RP FUNCTION (NON-STRUCTURAL PROTEIN 1). RX PubMed=26562291; DOI=10.1371/journal.ppat.1005277; RA Scaturro P., Cortese M., Chatel-Chaix L., Fischl W., RA 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). CC -!- FUNCTION: Capsid protein C: Plays a role in virus budding by CC binding to the cell membrane and gathering the viral RNA into a CC nucleocapsid that forms the core of a mature virus particle. CC During virus entry, may induce genome penetration into the host CC cytoplasm after hemifusion induced by the surface proteins. Can CC migrate to the cell nucleus where it modulates host functions. CC Overcomes the anti-viral effects of host EXOC1 by sequestering and CC degrading the latter through the proteasome degradation pathway. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Capsid protein C: Inhibits RNA silencing by interfering CC with host Dicer. {ECO:0000250|UniProtKB:P03314}. CC -!- FUNCTION: Peptide pr: Prevents premature fusion activity of CC envelope proteins in trans-Golgi by binding to envelope protein E CC at pH6.0. After virion release in extracellular space, gets CC dissociated from E dimers. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Protein prM: Acts as a chaperone for envelope protein E CC during intracellular virion assembly by masking and inactivating CC envelope protein E fusion peptide. prM is the only viral peptide CC matured by host furin in the trans-Golgi network probably to avoid CC catastrophic activation of the viral fusion activity in acidic CC Golgi compartment prior to virion release. prM-E cleavage is CC inefficient, and many virions are only partially matured. These CC uncleaved prM would play a role in immune evasion. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Small envelope protein M: May play a role in virus CC budding. Exerts cytotoxic effects by activating a mitochondrial CC apoptotic pathway through M ectodomain. May display a viroporin CC activity. {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Envelope protein E: Binds to host cell surface receptor CC and mediates fusion between viral and cellular membranes. Envelope CC protein is synthesized in the endoplasmic reticulum in the form of CC heterodimer with protein prM. They play a role in virion budding CC in the ER, and the newly formed immature particle is covered with CC 60 spikes composed of heterodimer between precursor prM and CC envelope protein E. The virion is transported to the Golgi CC apparatus where the low pH causes dissociation of PrM-E CC heterodimers and formation of E homodimers. prM-E cleavage is CC inefficient, and many virions are only partially matured. These CC uncleaved prM would play a role in immune evasion. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Non-structural protein 1: Involved in immune evasion, CC pathogenesis and viral replication. Once cleaved off the CC polyprotein, is targeted to three destinations: the viral CC replication cycle, the plasma membrane and the extracellular CC compartment. Essential for viral replication. Required for CC formation of the replication complex and recruitment of other non- CC structural proteins to the ER-derived membrane structures. CC Excreted as a hexameric lipoparticle that plays a role against CC host immune response. Antagonizing the complement function. Binds CC 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 CC cells, inducing degradation of sialic acid and shedding of heparan CC sulfate proteoglycans. NS1 induces expression of sialidases, CC heparanase, and activates cathepsin L, which activates heparanase CC via enzymatic cleavage. These effects are probably linked to the CC endothelial hyperpermeability observed in severe dengue disease. CC {ECO:0000250|UniProtKB:P17763}. CC -!- FUNCTION: Non-structural protein 2A: Component of the viral RNA CC replication complex that functions in virion assembly and CC antagonizes the host immune response. CC {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- CC ProRule:PRU00859}. CC -!- FUNCTION: Serine protease NS3: Displays three enzymatic CC activities: serine protease, NTPase and RNA helicase. NS3 serine CC protease, in association with NS2B, performs its autocleavage and CC cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, CC NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA CC helicase binds RNA and unwinds dsRNA in the 3' to 5' direction. CC {ECO:0000255|PROSITE-ProRule:PRU00860}. CC -!- FUNCTION: Non-structural protein 4A: Regulates the ATPase activity CC of the NS3 helicase activity. NS4A allows NS3 helicase to conserve CC energy during unwinding. Plays a role in the inhibition of the CC host innate immune response. Interacts with host MAVS and thereby CC prevents the interaction between DDX58 and MAVS. In turn, IFN-beta CC production is impaired. {ECO:0000250|UniProtKB:P17763, CC ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: Peptide 2k: Functions as a signal peptide for NS4B and CC is 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 CC cellular antiviral state by blocking the IFN-alpha/beta pathway. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- FUNCTION: RNA-directed RNA polymerase NS5: Replicates the viral CC (+) and (-) RNA genome, and performs the capping of genomes in the CC cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose CC 2'-O positions. Besides its role in RNA genome replication, also CC prevents the establishment of cellular antiviral state by blocking CC the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. CC Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing CC activation of JAK-STAT signaling pathway. CC {ECO:0000250|UniProtKB:P17763}. CC -!- CATALYTIC ACTIVITY: Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds CC in which each of the Xaa can be either Arg or Lys and Yaa can be CC either Ser or Ala. CC -!- CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate CC + RNA(n+1). {ECO:0000255|PROSITE-ProRule:PRU00539}. CC -!- CATALYTIC ACTIVITY: NTP + H(2)O = NDP + phosphate. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + G(5')pppR-RNA = S- CC adenosyl-L-homocysteine + m(7)G(5')pppR-RNA. {ECO:0000255|PROSITE- CC ProRule:PRU00924}. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + a 5'-(N(7)-methyl CC 5'-triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] = S- CC adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'- CC triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)-[mRNA]. CC {ECO:0000255|PROSITE-ProRule:PRU00924}. CC -!- SUBUNIT: Capsid protein C: Homodimer. Interacts (via N-terminus) CC with host EXOC1 (via C-terminus); this interaction results in CC EXOC1 degradation through the proteasome degradation pathway. CC Protein prM: Forms heterodimers with envelope protein E in the CC endoplasmic reticulum and Golgi. Envelope protein E: Homodimer; in CC the endoplasmic reticulum and Golgi. Interacts with protein prM. CC Interacts with non-structural protein 1. Non-structural protein 1: CC Homodimer; Homohexamer when secreted. Interacts with envelope CC protein E. Non-structural protein 2A: Interacts (via N-terminus) CC with serine protease NS3. Non-structural protein 2B: Forms a CC heterodimer with serine protease NS3. May form homooligomers. CC Serine protease NS3: Forms a heterodimer with NS2B. Interacts with CC NS4B. Interacts with unphosphorylated RNA-directed RNA polymerase CC NS5; this interaction stimulates RNA-directed RNA polymerase NS5 CC guanylyltransferase activity. Non-structural protein 4A: Interacts CC with host MAVS; this interaction inhibits the synthesis of IFN- CC beta. Non-structural protein 4B: Interacts with serine protease CC NS3. RNA-directed RNA polymerase NS5: Homodimer. Interacts with CC host STAT2; this interaction inhibits the phosphorylation of the CC latter, and, when all viral proteins are present (polyprotein), CC targets STAT2 for degradation. Interacts with serine protease NS3. CC {ECO:0000250|UniProtKB:P17763}. CC -!- INTERACTION: CC Q9ULX6:AKAP8L (xeno); NbExp=3; IntAct=EBI-8826747, EBI-357530; CC Q9ULJ7:ANKRD50 (xeno); NbExp=4; IntAct=EBI-8826747, EBI-5653671; CC P04114:APOB (xeno); NbExp=3; IntAct=EBI-8826488, EBI-3926040; CC P61201:COPS2 (xeno); NbExp=3; IntAct=EBI-8826488, EBI-1050386; CC Q92564:DCUN1D4 (xeno); NbExp=3; IntAct=EBI-8826488, EBI-2654610; CC A8MPP1:DDX11L8 (xeno); NbExp=3; IntAct=EBI-8826747, EBI-5463183; CC P17844:DDX5 (xeno); NbExp=3; IntAct=EBI-8826747, EBI-351962; CC Q03001:DST (xeno); NbExp=4; IntAct=EBI-8826488, EBI-310758; CC P78344:EIF4G2 (xeno); NbExp=4; IntAct=EBI-8826747, EBI-296519; CC Q08379:GOLGA2 (xeno); NbExp=3; IntAct=EBI-8826488, EBI-618309; CC A6NCC3:GOLGA8O (xeno); NbExp=3; IntAct=EBI-8826747, EBI-8827490; CC Q8WUM4:PDCD6IP (xeno); NbExp=3; IntAct=EBI-8826747, EBI-310624; CC O75925:PIAS1 (xeno); NbExp=3; IntAct=EBI-8826488, EBI-629434; CC P30041:PRDX6 (xeno); NbExp=3; IntAct=EBI-8826747, EBI-2255129; CC P26599:PTBP1 (xeno); NbExp=3; IntAct=EBI-8826747, EBI-350540; CC P63279:UBE2I (xeno); NbExp=3; IntAct=EBI-8826488, EBI-80168; CC -!- SUBCELLULAR LOCATION: Capsid protein C: Virion CC {ECO:0000250|UniProtKB:P17763}. Host nucleus CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear CC region {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Peptide pr: Secreted CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. Host endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. Host endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum CC membrane; Peripheral membrane protein; Lumenal side CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived CC vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host CC endoplasmic reticulum membrane; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Serine protease NS3: Host endoplasmic CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; CC Peripheral membrane protein {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Cytoplasmic side {ECO:0000255|PROSITE- CC ProRule:PRU00860}. Note=Remains non-covalently associated to CC 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 CC membrane protein {ECO:0000250|UniProtKB:P17763}. Host CC mitochondrion {ECO:0000250|UniProtKB:P17763}. Note=Located in RE- CC associated vesicles hosting the replication complex. Interacts CC with host MAVS in the mitochondrion-associated endoplasmic CC reticulum membranes. {ECO:0000250|UniProtKB:P17763}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P17763}. Note=Located in CC RE-derived vesicles hosting the replication complex. CC {ECO:0000250|UniProtKB:Q9Q6P4}. CC -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host CC endoplasmic reticulum membrane; Peripheral membrane protein; CC Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}. CC Note=Located in RE-associated vesicles hosting the replication CC complex. NS5 protein is mainly localized in the nucleus rather CC than in ER vesicles, especially in the DENV 2, 3, 4 serotypes. CC {ECO:0000250|UniProtKB:P17763}. CC -!- DOMAIN: The transmembrane domains of the small envelope protein M CC and envelope protein E contain an endoplasmic reticulum retention CC signal. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: Genome polyprotein: Specific enzymatic cleavages in vivo CC yield mature proteins. Cleavages in the lumen of endoplasmic CC reticulum are performed by host signal peptidase, whereas CC cleavages in the cytoplasmic side are performed by serine protease CC NS3. Signal cleavage at the 2K-4B site requires a prior NS3 CC protease-mediated cleavage at the 4A-2K site. CC {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: Protein prM: Cleaved in post-Golgi vesicles by a host furin, CC releasing the mature small envelope protein M, and peptide pr. CC This cleavage is incomplete as up to 30% of viral particles still CC carry 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 CC is glycosylated and this is required for efficient secretion of CC the protein from infected cells. {ECO:0000250|UniProtKB:P17763}. CC -!- PTM: RNA-directed RNA polymerase NS5: Sumoylation of RNA-directed CC RNA polymerase NS5 increases NS5 protein stability allowing proper CC viral RNA replication. {ECO:0000250|UniProtKB:P29990}. CC -!- PTM: RNA-directed RNA polymerase NS5: Phosphorylated on serines CC residues. This phosphorylation may trigger NS5 nuclear CC localization. {ECO:0000250|UniProtKB:P17763}. CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like CC SAM-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="http://www.viprbrc.org/brc/home.do?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; M84728; AAA73186.1; -; Genomic_RNA. DR PIR; B42451; GNWV26. DR PDB; 2R29; X-ray; 3.00 A; A=578-674. DR PDB; 3EVG; X-ray; 2.20 A; A=2493-2757. DR PDBsum; 2R29; -. DR PDBsum; 3EVG; -. DR ProteinModelPortal; P29991; -. DR SMR; P29991; -. DR IntAct; P29991; 107. DR OrthoDB; VOG09000016; -. DR EvolutionaryTrace; P29991; -. DR PRO; PR:P29991; -. DR Proteomes; UP000008390; Genome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW. DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008026; F:ATP-dependent helicase activity; IEA:InterPro. 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:InterPro. 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:0070008; F:serine-type exopeptidase 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; IEA:UniProtKB-KW. DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW. DR GO; GO:0051259; P:protein oligomerization; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0039545; P:suppression by virus of host MAVS activity; IEA:UniProtKB-KW. DR GO; GO:0039564; P:suppression by virus of host STAT2 activity; IEA:UniProtKB-KW. DR GO; GO:0039574; P:suppression by virus of host TYK2 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:0006351; P:transcription, DNA-templated; 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; 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; 2.60.260.50; -; 1. DR Gene3D; 2.60.40.350; -; 1. DR Gene3D; 2.60.98.10; -; 3. DR Gene3D; 3.30.387.10; -; 2. DR Gene3D; 3.30.67.10; -; 4. DR InterPro; IPR011492; DEAD_Flavivir. DR InterPro; IPR000069; Env_glycoprot_M_flavivir. DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir. DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1. DR InterPro; IPR001122; Flavi_capsidC. DR InterPro; IPR037172; Flavi_capsidC_sf. DR InterPro; IPR027287; Flavi_E_Ig-like. DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom. DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf. DR InterPro; IPR001157; Flavi_NS1. DR InterPro; IPR000752; Flavi_NS2A. DR InterPro; IPR000487; Flavi_NS2B. DR InterPro; IPR000404; Flavi_NS4A. DR InterPro; IPR001528; Flavi_NS4B. DR InterPro; IPR002535; Flavi_propep. DR InterPro; IPR038688; Flavi_propep_sf. DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf. DR InterPro; IPR001850; Flavivirus_NS3_S7. DR InterPro; IPR014412; Gen_Poly_FLV. DR InterPro; IPR011998; Glycoprot_cen/dimer. DR InterPro; IPR036253; Glycoprot_cen/dimer_sf. DR InterPro; IPR038055; Glycoprot_E_dimer_dom. DR InterPro; IPR013756; GlyE_cen_dom_subdom2. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR000208; RNA-dir_pol_flavivirus. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR002877; rRNA_MeTrfase_FtsJ_dom. DR InterPro; IPR029063; SAM-dependent_MTases. 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; 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; 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; Complete proteome; 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; KW 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; KW Methyltransferase; mRNA capping; mRNA processing; KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; KW Phosphoprotein; Protease; RNA-binding; RNA-directed RNA polymerase; KW S-adenosyl-L-methionine; Secreted; Serine protease; KW Suppressor of RNA silencing; Transcription; Transcription regulation; KW Transferase; Transmembrane; Transmembrane helix; Transport; KW 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 3391 Genome polyprotein. FT /FTId=PRO_0000405214. FT CHAIN 1 100 Capsid protein C. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037936. FT PROPEP 101 114 ER anchor for the Capsid protein C, FT removed in mature form by serine protease FT NS3. {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037937. FT PROPEP 101 114 ER anchor for the capsid protein C, FT removed in mature form by serine protease FT NS3. {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000441419. FT CHAIN 115 280 Protein prM. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000308279. FT CHAIN 115 205 Peptide pr. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000308280. FT CHAIN 206 280 Small envelope protein M. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037938. FT CHAIN 281 775 Envelope protein E. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037939. FT CHAIN 776 1127 Non-structural protein 1. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037940. FT CHAIN 1128 1345 Non-structural protein 2A. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037941. FT CHAIN 1346 1475 Serine protease subunit NS2B. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037943. FT CHAIN 1476 2093 Serine protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000308465. FT CHAIN 2094 2220 Non-structural protein 4A. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037944. FT PEPTIDE 2221 2243 Peptide 2k. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000308281. FT CHAIN 2244 2491 Non-structural protein 4B. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037945. FT CHAIN 2492 3391 RNA-directed RNA polymerase NS5. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000037946. FT TOPO_DOM 1 101 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 102 122 Helical. {ECO:0000255}. FT TOPO_DOM 123 242 Extracellular. {ECO:0000255}. FT TRANSMEM 243 260 Helical. {ECO:0000255}. FT TOPO_DOM 261 261 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 262 280 Helical. {ECO:0000255}. FT TOPO_DOM 281 727 Extracellular. {ECO:0000255}. FT TRANSMEM 728 748 Helical. {ECO:0000255}. FT TOPO_DOM 749 752 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 753 773 Helical. {ECO:0000255}. FT TOPO_DOM 774 1195 Extracellular. {ECO:0000255}. FT TRANSMEM 1196 1220 Helical. {ECO:0000255}. FT TOPO_DOM 1221 1226 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1227 1245 Helical. {ECO:0000255}. FT TOPO_DOM 1246 1269 Lumenal. {ECO:0000255}. FT TRANSMEM 1270 1290 Helical. {ECO:0000255}. FT TOPO_DOM 1291 1291 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1292 1310 Helical. {ECO:0000255}. FT TOPO_DOM 1311 1317 Lumenal. {ECO:0000255}. FT TRANSMEM 1318 1338 Helical. {ECO:0000255}. FT TOPO_DOM 1339 1346 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1347 1367 Helical. {ECO:0000255}. FT TOPO_DOM 1368 1370 Lumenal. {ECO:0000255}. FT TRANSMEM 1371 1391 Helical. {ECO:0000255}. FT TOPO_DOM 1392 1447 Cytoplasmic. {ECO:0000255}. FT INTRAMEM 1448 1468 Helical. {ECO:0000255}. FT TOPO_DOM 1469 2147 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2148 2168 Helical. {ECO:0000255}. FT TOPO_DOM 2169 2170 Lumenal. {ECO:0000255}. FT INTRAMEM 2171 2191 Helical. {ECO:0000255}. FT TOPO_DOM 2192 2192 Lumenal. {ECO:0000255}. FT TRANSMEM 2193 2213 Helical. {ECO:0000255}. FT TOPO_DOM 2214 2228 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2229 2249 Helical; Note=Signal for NS4B. FT {ECO:0000255}. FT TOPO_DOM 2250 2274 Lumenal. {ECO:0000255}. FT INTRAMEM 2275 2295 Helical. {ECO:0000255}. FT TOPO_DOM 2296 2316 Lumenal. {ECO:0000255}. FT INTRAMEM 2317 2337 Helical. {ECO:0000255}. FT TOPO_DOM 2338 2347 Lumenal. {ECO:0000255}. FT TRANSMEM 2348 2368 Helical. {ECO:0000255}. FT TOPO_DOM 2369 2413 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2414 2434 Helical. {ECO:0000255}. FT TOPO_DOM 2435 2459 Lumenal. {ECO:0000255}. FT TRANSMEM 2460 2480 Helical. {ECO:0000255}. FT TOPO_DOM 2481 3391 Cytoplasmic. {ECO:0000255}. FT DOMAIN 1476 1653 Peptidase S7. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT DOMAIN 1655 1811 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 1821 1988 Helicase C-terminal. FT DOMAIN 2493 2755 mRNA cap 0-1 NS5-type MT. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT DOMAIN 3020 3169 RdRp catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU00539}. FT NP_BIND 1668 1675 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 1 15 Interaction with host EXOC1. FT {ECO:0000250|UniProtKB:P17763}. FT REGION 37 72 Hydrophobic; homodimerization of capsid FT protein C. FT {ECO:0000250|UniProtKB:P29990}. FT REGION 378 391 Fusion peptide. FT {ECO:0000250|UniProtKB:P14336}. FT REGION 1398 1437 Interacts with and activates NS3 FT protease. {ECO:0000255|PROSITE- FT ProRule:PRU00859}. FT REGION 1659 1662 Important for RNA-binding. FT {ECO:0000250|UniProtKB:P14340}. FT MOTIF 1759 1762 DEAH box. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT MOTIF 2568 2571 SUMO-interacting motif. FT {ECO:0000250|UniProtKB:P29990}. FT COMPBIAS 97 100 Poly-Arg. FT COMPBIAS 1434 1437 Poly-Glu. FT COMPBIAS 2148 2154 Poly-Leu. FT COMPBIAS 3383 3386 Poly-Glu. FT ACT_SITE 1526 1526 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1550 1550 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1610 1610 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 2552 2552 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2637 2637 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2672 2672 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2708 2708 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2929 2929 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2933 2933 Zinc 1; via tele nitrogen. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2938 2938 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2941 2941 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3203 3203 Zinc 2; via tele nitrogen. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3219 3219 Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3338 3338 Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}. FT BINDING 2505 2505 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2508 2508 mRNA cap; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2509 2509 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2511 2511 mRNA cap; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2520 2520 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2547 2547 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2577 2577 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2578 2578 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2595 2595 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2596 2596 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2622 2622 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2623 2623 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2641 2641 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2703 2703 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2705 2705 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2710 2710 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 100 101 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 114 115 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 205 206 Cleavage; by host furin. FT {ECO:0000250|UniProtKB:P29990, FT ECO:0000255}. FT SITE 280 281 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 775 776 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1127 1128 Cleavage; by host. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1345 1346 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1475 1476 Cleavage; by autolysis. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1932 1932 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 1935 1935 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 2093 2094 Cleavage; by autolysis. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2220 2221 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2243 2244 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2491 2492 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2516 2516 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2552 2552 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2637 2637 Essential for 2'-O-methyltransferase and FT N-7 methyltransferase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2638 2638 S-adenosyl-L-methionine binding. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2672 2672 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2708 2708 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT MOD_RES 2547 2547 Phosphoserine. FT {ECO:0000250|UniProtKB:P03314}. FT CARBOHYD 183 183 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 347 347 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 433 433 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 905 905 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 982 982 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 1134 1134 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 2301 2301 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 2305 2305 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 2457 2457 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT DISULFID 283 310 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 340 401 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 354 385 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 372 396 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 465 565 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 582 613 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 779 790 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 830 918 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 954 998 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1055 1104 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1066 1088 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1087 1091 {ECO:0000250|UniProtKB:P17763}. FT STRAND 584 594 {ECO:0000244|PDB:2R29}. FT STRAND 600 609 {ECO:0000244|PDB:2R29}. FT STRAND 633 635 {ECO:0000244|PDB:2R29}. FT STRAND 641 643 {ECO:0000244|PDB:2R29}. FT STRAND 660 665 {ECO:0000244|PDB:2R29}. FT HELIX 2500 2509 {ECO:0000244|PDB:3EVG}. FT HELIX 2513 2521 {ECO:0000244|PDB:3EVG}. FT STRAND 2525 2528 {ECO:0000244|PDB:3EVG}. FT HELIX 2530 2537 {ECO:0000244|PDB:3EVG}. FT HELIX 2549 2557 {ECO:0000244|PDB:3EVG}. FT TURN 2558 2560 {ECO:0000244|PDB:3EVG}. FT STRAND 2566 2571 {ECO:0000244|PDB:3EVG}. FT HELIX 2577 2583 {ECO:0000244|PDB:3EVG}. FT STRAND 2588 2594 {ECO:0000244|PDB:3EVG}. FT HELIX 2612 2614 {ECO:0000244|PDB:3EVG}. FT STRAND 2615 2618 {ECO:0000244|PDB:3EVG}. FT HELIX 2623 2625 {ECO:0000244|PDB:3EVG}. FT STRAND 2632 2636 {ECO:0000244|PDB:3EVG}. FT HELIX 2645 2662 {ECO:0000244|PDB:3EVG}. FT STRAND 2668 2674 {ECO:0000244|PDB:3EVG}. FT HELIX 2679 2692 {ECO:0000244|PDB:3EVG}. FT STRAND 2695 2697 {ECO:0000244|PDB:3EVG}. FT STRAND 2709 2712 {ECO:0000244|PDB:3EVG}. FT HELIX 2719 2732 {ECO:0000244|PDB:3EVG}. FT HELIX 2733 2735 {ECO:0000244|PDB:3EVG}. FT STRAND 2742 2745 {ECO:0000244|PDB:3EVG}. SQ SEQUENCE 3391 AA; 379884 MW; 5EE11A74081C5177 CRC64; MNDQRKEAKN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLYMAL VAFLRFLTIP PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR SAGMIIMLIP TVMAFHLTTR NGEPHMIVSR QEKGKSLLFK TEVGVNMCTL MAMDLGELCE DTITYKCPLL RQNEPEDIDC WCNSTSTWVT YGTCTTMGEH RREKRSVALV PHVGMGLETR TETWMSSEGA WKHVQRIETW ILRHPGFTMM AAILAYTIGT THFQRALILI LLTAVTPSMT MRCIGMSNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFR CKKNMEGKVV QPENLEYTIV ITPHSGEEHA VGNDTGKHGK EIKITPQSSI TEAELTGYGT ITMECSPRTG LDFNEIVLLQ MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE PPFGDSYIII GVEPGQLKLN WFKKGSSIGQ MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVTLV LVGIVTLYLG VMVQADSGCV VSWKNKELKC GSGIFITDNV HTWTEQYKFQ PESPSKLASA IQKAHEEDIC GIRSVTRLEN LMWKQITPEL NHILSENEVK LTIMTGDIKG IMQAGKRSLR PQPTELKYSW KTWGKAKMLS TESHNQTFFI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLKEKQ DVFCDSKLMS AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKNCHW PKSHTLWSNG VLESEMIIPK NLAGPVSKHN YRPGYHTQIT GPWHLGKLEM DFDFCDGTTV VVTEDCGNRG PSLRTTTASG KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QVDNFSLGVL GMALFLEEML RTRVGTKHAI LLVAVSFVTL IIGNRSFRDL GRVMVMVGAT MTDDIGMGVT YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLSSQ STIPETILEL TDALALGMMV LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKTDWIP LALTIKGLNP TAIFLTTLSR TSKKRSWPLN EAIMAVGMVS ILASSLLKND IPMTGPLVAG GLLTVCYVLT GRSADLELER AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL TILIRRGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPMGK AELEDGAYRI KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL EGEWKEGEEV QVLALDPGKN PRAVQTKPGL FKTNAGTIGA VSLDFSPGTS GSPIIDKKGK VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF TMRLLSPVRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF PQSNAPIIDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KAGNDIAACL RKNGKKVIQL SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG PMPVTHSSAA QRRGRIGRNP KNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII PSMFEPEREK VDAIDGEYRL RGEARTTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD GVKNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRKSLTLNLI TEMGRLPTFM TQKARNALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL LTLLATVTGG IFLFLMSARG IGKMTLGMCC IITASILLWY AQIQPHWIAA SIILEFFLIV LLIPEPEKQR TPQDNQLTYV VIAILTVVAA TMANEMGFLE KTKKDLGLGS IATQQPESNI LDIDLRPASA WTLYAVATTF VTPMLRHSIE NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG CYSQVNPTTL TAALFLLVAH YAIIGPALQA KASREAQKRA AAGIMKNPTV DGITVIDLDP IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEALTLA TGPISTLSEG NPGRFWNTTI AVSMANIFRG SYLAGAGLLF SIMKNTTNTR RVTGNIGETL GEKWKSRLNA LGKSEFQIYK KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS AKLRWFVERN MVTPEGKVVD LGCGRGGWSY YCGGLKNVRE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFIPPEK CDTLLCDIGE SSPNPTVEAG RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP LSRNSTHEMY WVSNASGNIV SSVNMISRML INRFTMRYKK ATYEPDVDLG SGTRNIGIES EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY ETKQTGSASS MVNGVFRLLT KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV DTRTQEPKEG TKKLMKITAE WLWKELGKKK TPRMCTREEF TRKVRSNAAL GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET CVYNIMGKRE KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EEMVTNHMEG EHKKLAEAIF KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL NTFTNMEAQL IRQMEGEGVF KSIQHLTITE EIAVQNWLAR VGRERLSRMA ISGDDCVVKP LDDRLPSALT ALNDMGKIRK DIQQWEPSRG WNDWTQVPFC SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR ETACLGKSYA QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW AKNIQAAINQ VRSLIGNEEY TDYMPSMKRF RREEEEAGVL W //