ID POLG_DEN4T Reviewed; 3387 AA. AC Q2YHF0; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2005, sequence version 1. DT 22-NOV-2017, entry version 106. 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 4 (strain Thailand/0348/1991) (DENV-4). OC Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; OC Flaviviridae; Flavivirus; Dengue virus group. OX NCBI_TaxID=408688; OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti). OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta). OH NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito). OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=15476884; DOI=10.1016/j.virol.2004.08.003; RA Klungthong C., Zhang C., Mammen M.P. Jr., Ubol S., Holmes E.C.; RT "The molecular epidemiology of dengue virus serotype 4 in Bangkok, RT Thailand."; RL Virology 329:168-179(2004). RN [2] RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 1646-2092. RX PubMed=19008861; DOI=10.1038/emboj.2008.232; RA Luo D., Xu T., Watson R.P., Scherer-Becker D., Sampath A., Jahnke W., RA Yeong S.S., Wang C.H., Lim S.P., Strongin A., Vasudevan S.G., RA Lescar J.; RT "Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 RT protein."; RL EMBO J. 27:3209-3219(2008). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1393-2092, AND TOPOLOGY RP (NON-STRUCTURAL PROTEIN 2B). RX PubMed=20375022; DOI=10.1074/jbc.M109.090936; RA Luo D., Wei N., Doan D.N., Paradkar P.N., Chong Y., Davidson A.D., RA Kotaka M., Lescar J., Vasudevan S.G.; RT "Flexibility between the protease and helicase domains of the dengue RT virus NS3 protein conferred by the linker region and its functional RT implications."; RL J. Biol. Chem. 285:18817-18827(2010). 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 -!- 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; AY618990; AAU89377.1; -; Genomic_RNA. DR PDB; 2JLQ; X-ray; 1.67 A; A=1646-2092. DR PDB; 2JLR; X-ray; 2.00 A; A=1646-2092. DR PDB; 2JLS; X-ray; 2.23 A; A=1646-2092. DR PDB; 2JLU; X-ray; 2.04 A; A/B=1646-2092. DR PDB; 2JLV; X-ray; 2.30 A; A/B=1646-2092. DR PDB; 2JLW; X-ray; 2.60 A; A/B=1646-2092. DR PDB; 2JLX; X-ray; 2.20 A; A/B=1646-2092. DR PDB; 2JLY; X-ray; 2.40 A; A/B=1646-2092. DR PDB; 2JLZ; X-ray; 2.20 A; A/B=1646-2092. DR PDB; 2WHX; X-ray; 2.20 A; A=1475-2092, C=1393-1406. DR PDB; 2WZQ; X-ray; 2.80 A; A=1475-2092, C=1393-1410. DR PDB; 3UYP; X-ray; 2.00 A; B=575-679. DR PDBsum; 2JLQ; -. DR PDBsum; 2JLR; -. DR PDBsum; 2JLS; -. DR PDBsum; 2JLU; -. DR PDBsum; 2JLV; -. DR PDBsum; 2JLW; -. DR PDBsum; 2JLX; -. DR PDBsum; 2JLY; -. DR PDBsum; 2JLZ; -. DR PDBsum; 2WHX; -. DR PDBsum; 2WZQ; -. DR PDBsum; 3UYP; -. DR ProteinModelPortal; Q2YHF0; -. DR SMR; Q2YHF0; -. DR MEROPS; S07.001; -. DR PRIDE; Q2YHF0; -. DR OrthoDB; VOG090000PI; -. DR BRENDA; 3.4.21.91; 9641. DR EvolutionaryTrace; Q2YHF0; -. DR PRO; PR:Q2YHF0; -. DR Proteomes; UP000000273; Genome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO: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:0030683; P:evasion or tolerance by virus of host immune response; IMP:CACAO. 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: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; 2.60.40.350; -; 1. DR Gene3D; 3.30.387.10; -; 1. DR Gene3D; 3.30.67.10; -; 1. DR InterPro; IPR011492; DEAD_Flavivir. DR InterPro; IPR000069; Env_glycoprot_M_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; 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; 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; 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 3387 Genome polyprotein. FT /FTId=PRO_0000405229. FT CHAIN 1 99 Capsid protein C. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268131. FT PROPEP 100 113 ER anchor for the capsid protein C, FT removed in mature form by serine protease FT NS3. {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268132. FT CHAIN 114 279 Protein prM. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268133. FT CHAIN 114 204 Peptide pr. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268134. FT CHAIN 205 279 Small envelope protein M. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268135. FT CHAIN 280 774 Envelope protein E. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268136. FT CHAIN 775 1126 Non-structural protein 1. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268137. FT CHAIN 1127 1344 Non-structural protein 2A. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268138. FT CHAIN 1345 1474 Serine protease subunit NS2B. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268139. FT CHAIN 1475 2092 Serine protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268140. FT CHAIN 2093 2219 Non-structural protein 4A. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268141. FT PEPTIDE 2220 2242 Peptide 2k. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268142. FT CHAIN 2243 2487 Non-structural protein 4B. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268143. FT CHAIN 2488 3387 RNA-directed RNA polymerase NS5. FT {ECO:0000250|UniProtKB:P29990}. FT /FTId=PRO_0000268144. FT TOPO_DOM 1 100 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 101 117 Helical. {ECO:0000255}. FT TOPO_DOM 118 237 Extracellular. {ECO:0000255}. FT TRANSMEM 238 258 Helical. {ECO:0000255}. FT TOPO_DOM 259 265 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 266 279 Helical. {ECO:0000255}. FT TOPO_DOM 280 725 Extracellular. {ECO:0000255}. FT TRANSMEM 726 746 Helical. {ECO:0000255}. FT TOPO_DOM 747 753 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 754 774 Helical. {ECO:0000255}. FT TOPO_DOM 775 1194 Extracellular. {ECO:0000255}. FT TRANSMEM 1195 1218 Helical. {ECO:0000255}. FT TOPO_DOM 1219 1224 Lumenal. {ECO:0000255}. FT TRANSMEM 1225 1243 Helical. {ECO:0000255}. FT TOPO_DOM 1244 1267 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1268 1288 Helical. {ECO:0000255}. FT TOPO_DOM 1289 1289 Lumenal. {ECO:0000255}. FT TRANSMEM 1290 1308 Helical. {ECO:0000255}. FT TOPO_DOM 1309 1316 Lumenal. {ECO:0000255}. FT TRANSMEM 1317 1337 Helical. {ECO:0000255}. FT TOPO_DOM 1338 1345 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1346 1366 Helical. {ECO:0000305|PubMed:20375022}. FT TOPO_DOM 1367 1369 Lumenal. {ECO:0000305|PubMed:20375022}. FT TRANSMEM 1370 1390 Helical. {ECO:0000305|PubMed:20375022}. FT TOPO_DOM 1391 1437 Cytoplasmic. FT {ECO:0000305|PubMed:20375022}. FT INTRAMEM 1438 1458 Helical. {ECO:0000305|PubMed:20375022}. FT TOPO_DOM 1459 2143 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2144 2164 Helical. {ECO:0000255}. FT TOPO_DOM 2165 2169 Lumenal. {ECO:0000255}. FT INTRAMEM 2170 2190 Helical. {ECO:0000255}. FT TOPO_DOM 2191 2191 Lumenal. {ECO:0000255}. FT TRANSMEM 2192 2212 Helical. {ECO:0000255}. FT TOPO_DOM 2213 2225 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2226 2246 Helical; Note=Signal for NS4B. FT {ECO:0000255}. FT TOPO_DOM 2247 2270 Lumenal. {ECO:0000255}. FT INTRAMEM 2271 2291 Helical. {ECO:0000255}. FT TOPO_DOM 2292 2301 Lumenal. {ECO:0000255}. FT INTRAMEM 2302 2322 Helical. {ECO:0000255}. FT TOPO_DOM 2323 2343 Lumenal. {ECO:0000255}. FT TRANSMEM 2344 2364 Helical. {ECO:0000255}. FT TOPO_DOM 2365 2409 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2410 2430 Helical. {ECO:0000255}. FT TOPO_DOM 2431 2455 Lumenal. {ECO:0000255}. FT TRANSMEM 2456 2476 Helical. {ECO:0000255}. FT TOPO_DOM 2477 3387 Cytoplasmic. {ECO:0000255}. FT DOMAIN 1475 1652 Peptidase S7. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT DOMAIN 1654 1810 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 1820 1987 Helicase C-terminal. FT DOMAIN 2489 2751 mRNA cap 0-1 NS5-type MT. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT DOMAIN 3016 3166 RdRp catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU00539}. FT NP_BIND 1667 1674 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 36 71 Hydrophobic; homodimerization of capsid FT protein C. FT {ECO:0000250|UniProtKB:P29990}. FT REGION 377 390 Fusion peptide. FT {ECO:0000250|UniProtKB:P14336}. FT REGION 1397 1436 Interacts with and activates NS3 FT protease. {ECO:0000255|PROSITE- FT ProRule:PRU00859}. FT REGION 1658 1661 Important for RNA-binding. FT {ECO:0000250|UniProtKB:P14340}. FT MOTIF 1758 1761 DEAH box. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT MOTIF 2564 2567 SUMO-interacting motif. FT {ECO:0000250|UniProtKB:P29990}. FT ACT_SITE 1525 1525 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1549 1549 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 1609 1609 Charge relay system; for serine protease FT NS3 activity. {ECO:0000255|PROSITE- FT ProRule:PRU00860}. FT ACT_SITE 2548 2548 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2633 2633 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2668 2668 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT ACT_SITE 2704 2704 For 2'-O-MTase activity. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2925 2925 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2929 2929 Zinc 1; via tele nitrogen. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2934 2934 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 2937 2937 Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3200 3200 Zinc 2; via tele nitrogen. FT {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3216 3216 Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}. FT METAL 3335 3335 Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}. FT BINDING 2501 2501 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2504 2504 mRNA cap; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2505 2505 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2507 2507 mRNA cap; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2516 2516 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2543 2543 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2573 2573 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2574 2574 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2591 2591 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2592 2592 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2618 2618 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT BINDING 2619 2619 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2637 2637 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2699 2699 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2701 2701 mRNA cap. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT BINDING 2706 2706 S-adenosyl-L-methionine. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 99 100 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 113 114 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 204 205 Cleavage; by host furin. FT {ECO:0000250|UniProtKB:P29990, FT ECO:0000255}. FT SITE 279 280 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 774 775 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1126 1127 Cleavage; by host. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1344 1345 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1474 1475 Cleavage; by autolysis. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 1931 1931 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 1934 1934 Involved in NS3 ATPase and RTPase FT activities. FT {ECO:0000250|UniProtKB:P14335}. FT SITE 2092 2093 Cleavage; by autolysis. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2219 2220 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2242 2243 Cleavage; by host signal peptidase. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2487 2488 Cleavage; by viral protease NS3. FT {ECO:0000250|UniProtKB:P29990}. FT SITE 2512 2512 mRNA cap binding. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2548 2548 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2633 2633 Essential for 2'-O-methyltransferase and FT N-7 methyltransferase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2634 2634 S-adenosyl-L-methionine binding. FT {ECO:0000255|PROSITE-ProRule:PRU00924}. FT SITE 2668 2668 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT SITE 2704 2704 Essential for 2'-O-methyltransferase FT activity. {ECO:0000255|PROSITE- FT ProRule:PRU00924}. FT MOD_RES 2543 2543 Phosphoserine. FT {ECO:0000250|UniProtKB:P03314}. FT CARBOHYD 182 182 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 346 346 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 432 432 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 904 904 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 981 981 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT CARBOHYD 2297 2297 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 2453 2453 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT DISULFID 282 309 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 339 400 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 353 384 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 371 395 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 464 564 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 581 612 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 778 789 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 829 917 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 953 997 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1054 1103 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1065 1087 {ECO:0000250|UniProtKB:P17763}. FT DISULFID 1086 1090 {ECO:0000250|UniProtKB:P17763}. FT STRAND 585 589 {ECO:0000244|PDB:3UYP}. FT STRAND 599 605 {ECO:0000244|PDB:3UYP}. FT STRAND 607 609 {ECO:0000244|PDB:3UYP}. FT STRAND 611 613 {ECO:0000244|PDB:3UYP}. FT STRAND 616 619 {ECO:0000244|PDB:3UYP}. FT STRAND 625 630 {ECO:0000244|PDB:3UYP}. FT STRAND 632 634 {ECO:0000244|PDB:3UYP}. FT STRAND 639 642 {ECO:0000244|PDB:3UYP}. FT STRAND 644 649 {ECO:0000244|PDB:3UYP}. FT STRAND 652 661 {ECO:0000244|PDB:3UYP}. FT HELIX 662 664 {ECO:0000244|PDB:3UYP}. FT STRAND 665 672 {ECO:0000244|PDB:3UYP}. FT STRAND 1395 1401 {ECO:0000244|PDB:2WHX}. FT STRAND 1496 1502 {ECO:0000244|PDB:2WHX}. FT STRAND 1507 1514 {ECO:0000244|PDB:2WHX}. FT STRAND 1516 1518 {ECO:0000244|PDB:2WHX}. FT STRAND 1520 1522 {ECO:0000244|PDB:2WHX}. FT HELIX 1524 1527 {ECO:0000244|PDB:2WHX}. FT STRAND 1541 1545 {ECO:0000244|PDB:2WHX}. FT TURN 1546 1549 {ECO:0000244|PDB:2WHX}. FT STRAND 1550 1556 {ECO:0000244|PDB:2WHX}. FT STRAND 1565 1567 {ECO:0000244|PDB:2WHX}. FT STRAND 1569 1573 {ECO:0000244|PDB:2WHX}. FT STRAND 1581 1585 {ECO:0000244|PDB:2WHX}. FT STRAND 1598 1600 {ECO:0000244|PDB:2WHX}. FT STRAND 1612 1614 {ECO:0000244|PDB:2WHX}. FT STRAND 1616 1618 {ECO:0000244|PDB:2WHX}. FT STRAND 1620 1623 {ECO:0000244|PDB:2WHX}. FT STRAND 1637 1640 {ECO:0000244|PDB:2WZQ}. FT STRAND 1645 1647 {ECO:0000244|PDB:2JLX}. FT HELIX 1654 1657 {ECO:0000244|PDB:2JLQ}. FT STRAND 1662 1665 {ECO:0000244|PDB:2JLQ}. FT STRAND 1669 1671 {ECO:0000244|PDB:2WZQ}. FT TURN 1673 1676 {ECO:0000244|PDB:2JLV}. FT HELIX 1677 1687 {ECO:0000244|PDB:2JLQ}. FT STRAND 1692 1698 {ECO:0000244|PDB:2JLQ}. FT HELIX 1699 1708 {ECO:0000244|PDB:2JLQ}. FT TURN 1709 1711 {ECO:0000244|PDB:2JLQ}. FT STRAND 1714 1716 {ECO:0000244|PDB:2JLQ}. FT STRAND 1727 1729 {ECO:0000244|PDB:2JLR}. FT STRAND 1731 1735 {ECO:0000244|PDB:2JLQ}. FT HELIX 1736 1745 {ECO:0000244|PDB:2JLQ}. FT STRAND 1753 1758 {ECO:0000244|PDB:2JLQ}. FT TURN 1759 1761 {ECO:0000244|PDB:2JLQ}. FT HELIX 1765 1779 {ECO:0000244|PDB:2JLQ}. FT STRAND 1784 1788 {ECO:0000244|PDB:2JLQ}. FT STRAND 1806 1810 {ECO:0000244|PDB:2JLQ}. FT STRAND 1819 1821 {ECO:0000244|PDB:2JLQ}. FT HELIX 1823 1827 {ECO:0000244|PDB:2JLQ}. FT STRAND 1832 1835 {ECO:0000244|PDB:2JLQ}. FT HELIX 1839 1850 {ECO:0000244|PDB:2JLQ}. FT TURN 1851 1853 {ECO:0000244|PDB:2JLQ}. FT STRAND 1856 1859 {ECO:0000244|PDB:2JLQ}. FT TURN 1861 1863 {ECO:0000244|PDB:2JLQ}. FT HELIX 1864 1867 {ECO:0000244|PDB:2JLQ}. FT HELIX 1868 1872 {ECO:0000244|PDB:2JLQ}. FT STRAND 1877 1881 {ECO:0000244|PDB:2JLQ}. FT HELIX 1883 1886 {ECO:0000244|PDB:2JLQ}. FT STRAND 1894 1898 {ECO:0000244|PDB:2JLQ}. FT STRAND 1901 1908 {ECO:0000244|PDB:2JLQ}. FT STRAND 1910 1912 {ECO:0000244|PDB:2JLQ}. FT STRAND 1914 1922 {ECO:0000244|PDB:2JLQ}. FT HELIX 1925 1932 {ECO:0000244|PDB:2JLQ}. FT STRAND 1935 1938 {ECO:0000244|PDB:2WZQ}. FT STRAND 1944 1948 {ECO:0000244|PDB:2JLQ}. FT HELIX 1960 1969 {ECO:0000244|PDB:2JLQ}. FT HELIX 1984 1989 {ECO:0000244|PDB:2JLQ}. FT TURN 1994 1997 {ECO:0000244|PDB:2JLQ}. FT HELIX 2001 2012 {ECO:0000244|PDB:2JLQ}. FT HELIX 2018 2026 {ECO:0000244|PDB:2JLQ}. FT HELIX 2035 2037 {ECO:0000244|PDB:2JLQ}. FT HELIX 2042 2044 {ECO:0000244|PDB:2JLQ}. FT STRAND 2047 2052 {ECO:0000244|PDB:2JLS}. FT STRAND 2054 2056 {ECO:0000244|PDB:2JLQ}. FT STRAND 2062 2064 {ECO:0000244|PDB:2JLQ}. FT HELIX 2072 2074 {ECO:0000244|PDB:2JLQ}. FT HELIX 2078 2088 {ECO:0000244|PDB:2JLQ}. SQ SEQUENCE 3387 AA; 378438 MW; 1FEDC2D663A0F945 CRC64; MNQRKKVARP PFNMLKRERN RVSTPQGLVK RFSTGLFSGK GPLRMVLAFI TFLRVLSIPP TAGILKRWGQ LKKNKAIKIL TGFRKEIGRM LNILNGRKRS TITLLCLIPT VMAFHLSTRD GEPLMIVAKH ERGRPLLFKT TEGINKCTLI AMDLGEMCED TVTYKCPLLV NTEPEDIDCW CNLTSAWVMY GTCTQSGERR REKRSVALTP HSGMGLETRA ETWMSSEGAW KHAQRVESWI LRNPGFALLA GFMAYMIGQT GIQRTVFFIL MMLVAPSYGM RCVGVGNRDF VEGVSGGAWV DLVLEHGGCV TTMAQGKPTL DFELIKTTAK EVALLRTYCI EASISNITTA TRCPTQGEPY LKEEQDQQYI CRRDMVDRGW GNGCGLFGKG GVVTCAKFSC SGKITGNLVQ IENLEYTVVV TVHNGDTHAV GNDTSNHGVT ATITPRSPSV EVKLPDYGEL TLDCEPRSGI DFNEMILMKM KTKTWLVHKQ WFLDLPLPWT AGADTLEVHW NHKERMVTFK VPHAKRQDVT VLGSQEGAMH SALAGATEVD SGDGNHMFAG HLKCKVRMEK LRIKGMSYTM CSGKFSIDKE MAETQHGTTV VKVKYEGTGA PCKVPIEIRD VNKEKVVGRI ISSTPFAENT NSVTNIELEP PFGDSYIVIG VGDSALTLHW FRKGSSIGKM FESTYRGAKR MAILGETAWD FGSVGGLLTS LGKAVHQVFG SVYTTMFGGV SWMVRILIGL LVLWIGTNSR NTSMAMSCIA VGGITLFLGF TVHADMGCAV SWSGKELKCG SGIFVIDNVH TWTEQYKFQP ESPARLASAI LNAHKDGVCG IRSTTRLENV MWKQITNELN YVLWEGGHDL TVVAGDVKGV LSKGKRALAP PVNDLKYSWK TWGKAKIFTP ETRNSTFLVD GPDTSECPNE RRAWNFLEVE DYGFGMFTTN IWMKFREGSS EVCDHRLMSA AIKDQKAVHA DMGYWIESSK NQTWQIEKAS LIEVKTCLWP KTHTLWSNGV LESQMLIPKA YAGPISQHNY RQGYATQTVG PWHLGKLEID FGECPGTTVT IQEDCDHRGP SLRTTTASGK LVTQWCCRSC TMPPLRFLGE DGCWYGMEIR PLNEKEENMV KSQVSAGQGT SETFSMGLLC LTLFVEECLR RRVTRKHMIL VVVTTLCAII LGGLTWMDLL RALIMLGDTM SGRMGGQIHL AIMAVFKMSP GYVLGIFLRK LTSRETALMV IGMAMTTVLS IPHDLMEFID GISLGLILLK MVTHFDNTQV GTLALSLTFI KSTMPLVMAW RTIMAVLFVV TLIPLCRTSC LQKQSHWVEI TALILGAQAL PVYLMTLMKG ASKRSWPLNE GIMAVGLVSL LGSALLKNDV PLAGPMVAGG LLLAAYVMSG SSADLSLEKA ANVQWDEMAD ITGSSPIIEV KQDEDGSFSI RDVEETNMIT LLVKLALITV SGLYPLAIPV TMTLWYMWQV KTQRSGALWD VPSPAAAQKA TLTEGVYRIM QRGLFGKTQV GVGIHMEGVF HTMWHVTRGS VICHESGRLE PSWADVRNDM ISYGGGWRLG DKWDKEEDVQ VLAIEPGKNP KHVQTKPGLF KTLTGEIGAV TLDFKPGTSG SPIINRKGKV IGLYGNGVVT KSGDYVSAIT QAERIGEPDY EVDEDIFRKK RLTIMDLHPG AGKTKRILPS IVREALKRRL RTLILAPTRV VAAEMEEALR GLPIRYQTPA VKSEHTGREI VDLMCHATFT TRLLSSTRVP NYNLIVMDEA HFTDPSSVAA RGYISTRVEM GEAAAIFMTA TPPGTTDPFP QSNSPIEDIE REIPERSWNT GFDWITDYQG KTVWFVPSIK AGNDIANCLR KSGKKVIQLS RKTFDTEYPK TKLTDWDFVV TTDISEMGAN FRAGRVIDPR RCLKPVILTD GPERVILAGP IPVTPASAAQ RRGRIGRNPA QEDDQYVFSG DPLRNDEDHA HWTEAKMLLD NIYTPEGIIP TLFGPEREKT QAIDGEFRLR GEQRKTFVEL MRRGDLPVWL SYKVASAGIS YKDREWCFTG ERNNQILEEN MEVEIWTREG EKKKLRPKWL DARVYADPMA LKDFKEFASG RKSITLDILT EIASLPTYLS SRAKLALDNI VMLHTTERGG KAYQHALNEL PESLETLMLV ALLGAMTAGI FLFFMQGKGI GKLSMGLIAI AVASGLLWVA EIQPQWIAAS IILEFFLMVL LVPEPEKQRT PQDNQLIYVI LTILTIIALV AANEMGLIEK TKTDFGFYQA KTETTILDVD LRPASAWTLY AVATTILTPM LRHTIENTSA NLSLAAIANQ AAVLMGLGKG WPLHRMDLGV PLLAMGCYSQ VNPTTLTASL VMLLVHYAII GPGLQAKATR EAQKRTAAGI MKNPTVDGIT VIDLEPISYD PKFEKQLGQV MLLVLCAGQL LLMRTTWAFC EVLTLATGPI LTLWEGNPGR FWNTTIAVST ANIFRGSYLA GAGLAFSLIK NAQTPRRGTG TTGETLGEKW KRQLNSLDRK EFEEYKRSGI LEVDRTEAKS ALKDGSKIKY AVSRGTSKIR WIVERGMVKP KGKVVDLGCG RGGWSYYMAT LKNVTEVKGY TKGGPGHEEP IPMATYGWNL VKLHSGVDVF YKPTEQVDTL LCDIGESSSN PTIEEGRTLR VLKMVEPWLS SKPEFCIKVL NPYMPTVIEE LEKLQRKHGG SLVRCPLSRN STHEMYWVSG VSGNIVSSVN TTSKMLLNRF TTRHRKPTYE KDADLGAGTR SVSTETEKPD MTIIGRRLQR LQEEHKETWH YDHENPYRTW AYHGSYEAPS TGSASSMVNG VVKLLTKPWD VVPMVTQLAM TDTTPFGQQR VFKEKVDTRT PQPKPGTRVV MTTTANWLWA LLGRKKNPRL CTREEFISKV RSNAAIGAVF QEEQGWTSAS EAVNDSRFWE LVDKERALHQ EGKCESCVYN MMGKREKKLG EFGRAKGSRA IWYMWLGARF LEFEALGFLN EDHWFGRENS WSGVEGEGLH RLGYILEDID KKDGDLIYAD DTAGWDTRIT EDDLLNEELI TEQMAPHHKI LAKAIFKLTY QNKVVKVLRP TPKGAVMDII SRKDQRGSGQ VGTYGLNTFT NMEVQLIRQM EAEGVITRDD MHNPKGLKER VEKWLKECGV DRLKRMAISG DDCVVKPLDE RFSTSLLFLN DMGKVRKDIP QWEPSKGWKN WQEVPFCSHH FHKIFMKDGR SLVVPCRNQD ELIGRARISQ GAGWSLRETA CLGKAYAQMW SLMYFHRRDL RLASMAICSA VPTEWFPTSR TTWSIHAHHQ WMTTEDMLKV WNRVWIEDNP NMIDKTPVHS WEDIPYLGKR EDLWCGSLIG LSSRATWAKN IQTAITQVRN LIGKEEYVDY MPVMKRYSAH FESEGVL //