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 16-SEP-2015, entry version 91. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Capsid protein C; DE AltName: Full=Core protein; DE Contains: DE RecName: Full=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=Non-structural protein 2A-alpha; 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; DE EC=3.6.4.13; 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; DE EC=2.1.1.57; DE EC=2.7.7.48; 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 OF RP NS2B. 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 self-assembles to form an icosahedral CC capsid about 30 nm in diameter. The capsid encapsulates the CC genomic RNA (By similarity). {ECO:0000250}. CC -!- FUNCTION: prM acts as a chaperone for envelope protein E during CC intracellular virion assembly by masking and inactivating envelope CC protein E fusion peptide. prM is matured in the last step of CC virion assembly, presumably to avoid catastrophic activation of CC the viral fusion peptide induced by the acidic pH of the trans- CC Golgi network. After cleavage by host furin, the pr peptide is CC released in the extracellular medium and small envelope protein M CC and envelope protein E homodimers are dissociated (By similarity). CC {ECO:0000250}. CC -!- FUNCTION: Envelope protein E binding to host cell surface receptor CC is followed by virus internalization through clathrin-mediated CC endocytosis. Envelope protein E is subsequently involved in CC membrane fusion between virion and host late endosomes. CC Synthesized as a homodimer with prM which acts as a chaperone for CC envelope protein E. After cleavage of prM, envelope protein E CC dissociate from small envelope protein M and homodimerizes (By CC similarity). {ECO:0000250}. CC -!- FUNCTION: Non-structural protein 1 is involved in virus CC replication and regulation of the innate immune response. Soluble CC and membrane-associated NS1 may activate human complement and CC induce host vascular leakage. This effect might explain the CC clinical manifestations of dengue hemorrhagic fever and dengue CC shock syndrome (By similarity). {ECO:0000250}. CC -!- FUNCTION: Non-structural protein 2A may be involved viral RNA CC replication and capsid assembly. {ECO:0000305}. CC -!- FUNCTION: Non-structural protein 2B is a required cofactor for the CC serine protease function of NS3. {ECO:0000255|PROSITE- CC 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, CC NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds CC RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). CC {ECO:0000255|PROSITE-ProRule:PRU00860}. CC -!- FUNCTION: Non-structural protein 4A induces host endoplasmic CC reticulum membrane rearrangements leading to the formation of CC virus-induced membranous vesicles hosting the dsRNA and CC polymerase, functioning as a replication complex. NS4A might also CC regulate the ATPase activity of the NS3 helicase (By similarity). CC {ECO:0000250}. 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}. CC -!- FUNCTION: Non-structural protein 4B inhibits interferon (IFN)- CC induced host STAT1 phosphorylation and nuclear translocation, CC thereby preventing the establishment of cellular antiviral state CC by blocking the IFN-alpha/beta pathway. {ECO:0000250}. CC -!- FUNCTION: RNA-directed RNA polymerase NS5 replicates the viral (+) CC and (-) 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 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 (By similarity). CC {ECO:0000255|PROSITE-ProRule:PRU00539}. 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 -!- SUBUNIT: Capsid protein C forms homodimers. prM and envelope CC protein E form heterodimers in the endoplasmic reticulum and CC Golgi. In immature particles, there are 60 icosaedrally organized CC trimeric spikes on the surface. Each spike consists of three CC heterodimers of envelope protein M precursor (prM) and envelope CC protein E. NS1 forms homodimers as well as homohexamers when CC secreted. NS1 may interact with NS4A. NS3 and NS2B form a CC heterodimer. NS3 is the catalytic subunit, whereas NS2B strongly CC stimulates the latter, acting as a cofactor. In the absence of the CC NS2B, NS3 protease is unfolded and inactive. NS3 interacts with CC unphosphorylated NS5; this interaction stimulates NS5 CC guanylyltransferase activity. NS5 interacts with host STAT2; this CC interaction inhibits the phosphorylation of the latter, and, when CC all viral proteins are present (polyprotein), targets STAT2 for CC degradation (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Capsid protein C: Virion {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Peptide pr: Secreted {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Multi-pass membrane protein {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Multi-pass membrane protein {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted. Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Peripheral membrane protein CC {ECO:0000255|PROSITE-ProRule:PRU00860}; Lumenal side CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A-alpha: Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Multi-pass membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Multi- CC pass membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Peripheral membrane protein CC {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side CC {ECO:0000255|PROSITE-ProRule:PRU00860}. 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 NS3 CC protease. {ECO:0000255|PROSITE-ProRule:PRU00860}. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4A: Host endoplasmic CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Multi- CC pass membrane protein {ECO:0000250}. Note=Located in RE-associated CC vesicles hosting the replication complex. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Multi- CC pass membrane protein {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host CC endoplasmic reticulum membrane {ECO:0000255|PROSITE- CC ProRule:PRU00860}; Peripheral membrane protein CC {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Host nucleus CC {ECO:0000250}. Note=Located in RE-associated vesicles hosting the CC replication complex. CC -!- DOMAIN: Transmembrane domains of the small envelope protein M and CC envelope protein E contains an endoplasmic reticulum retention CC signals. {ECO:0000250}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. CC The nascent protein C contains a C-terminal hydrophobic domain CC that act as a signal sequence for translocation of prM into the CC lumen of the ER. Mature protein C is cleaved at a site upstream of CC this hydrophobic domain by NS3. prM is cleaved in post-Golgi CC vesicles by a host furin, releasing the mature small envelope CC protein M, and peptide pr. Non-structural protein 2A-alpha, a C- CC terminally truncated form of non-structural protein 2A, results CC from partial cleavage by NS3. Peptide 2K acts as a signal sequence CC and is removed from the N-terminus of NS4B by the host signal CC peptidase in the ER lumen. Signal cleavage at the 2K-4B site CC requires a prior NS3 protease-mediated cleavage at the 4A-2K site CC (By similarity). {ECO:0000250}. CC -!- PTM: RNA-directed RNA polymerase NS5 is phosphorylated on serines CC residues. This phosphorylation may trigger NS5 nuclear CC localization (By similarity). {ECO:0000250}. CC -!- PTM: Envelope protein E and non-structural protein 1 are N- CC glycosylated. {ECO:0000250}. 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 -!- SIMILARITY: Contains 1 helicase ATP-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00541}. CC -!- SIMILARITY: Contains 1 helicase C-terminal domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 mRNA cap 0-1 NS5-type MT domain. CC {ECO:0000255|PROSITE-ProRule:PRU00924}. CC -!- SIMILARITY: Contains 1 peptidase S7 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00860}. CC -!- SIMILARITY: Contains 1 RdRp catalytic domain. CC {ECO:0000255|PROSITE-ProRule:PRU00539}. 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 MEROPS; S07.001; -. 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:0016021; C:integral component of membrane; 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: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:0003724; F:RNA helicase activity; IEA:InterPro. 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:0070008; F:serine-type exopeptidase activity; IEA:InterPro. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0075512; P:clathrin-mediated 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: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 Gene3D; 2.60.40.350; -; 1. DR Gene3D; 2.60.98.10; -; 2. DR Gene3D; 3.30.387.10; -; 1. DR Gene3D; 3.40.50.150; -; 1. DR Gene3D; 3.40.50.300; -; 2. 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; 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. DR InterPro; IPR001850; Flavivirus_NS3_S7. DR InterPro; IPR027287; Flavovir_Ig-like. DR InterPro; IPR014412; Gen_Poly_FLV. DR InterPro; IPR011998; Glycoprot_cen/dimer. DR InterPro; IPR013754; GlyE_dim. 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 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 endoplasmic reticulum; Host membrane; Host nucleus; KW Host-virus interaction; Hydrolase; KW Inhibition of host innate immune response by virus; KW Inhibition of host interferon signaling pathway by virus; KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus; KW Membrane; Metal-binding; Methyltransferase; mRNA capping; KW mRNA processing; Multifunctional enzyme; Nucleotide-binding; KW Nucleotidyltransferase; Phosphoprotein; Protease; RNA-binding; KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Secreted; KW Serine protease; Transcription; Transcription regulation; Transferase; KW Transmembrane; Transmembrane helix; Viral attachment to host cell; KW Viral envelope protein; Viral immunoevasion; KW Viral penetration into host cytoplasm; Viral RNA replication; Virion; KW Virus endocytosis by host; Virus entry into host cell. FT CHAIN 1 3387 Genome polyprotein. FT /FTId=PRO_0000405229. FT CHAIN 1 99 Capsid protein C. {ECO:0000250}. FT /FTId=PRO_0000268131. FT PROPEP 100 113 ER anchor for the protein C, removed in FT mature form by serine protease NS3. FT {ECO:0000250}. FT /FTId=PRO_0000268132. FT CHAIN 114 279 prM. {ECO:0000250}. FT /FTId=PRO_0000268133. FT CHAIN 114 204 Peptide pr. {ECO:0000250}. FT /FTId=PRO_0000268134. FT CHAIN 205 279 Small envelope protein M. {ECO:0000250}. FT /FTId=PRO_0000268135. FT CHAIN 280 774 Envelope protein E. {ECO:0000250}. FT /FTId=PRO_0000268136. FT CHAIN 775 1126 Non-structural protein 1. {ECO:0000250}. FT /FTId=PRO_0000268137. FT CHAIN 1127 1344 Non-structural protein 2A. {ECO:0000250}. FT /FTId=PRO_0000268138. FT CHAIN 1127 ? Non-structural protein 2A-alpha. FT {ECO:0000250}. FT /FTId=PRO_0000304550. FT CHAIN 1345 1474 Serine protease subunit NS2B. FT {ECO:0000250}. FT /FTId=PRO_0000268139. FT CHAIN 1475 2092 Serine protease NS3. {ECO:0000250}. FT /FTId=PRO_0000268140. FT CHAIN 2093 2219 Non-structural protein 4A. {ECO:0000250}. FT /FTId=PRO_0000268141. FT PEPTIDE 2220 2242 Peptide 2k. FT /FTId=PRO_0000268142. FT CHAIN 2243 2487 Non-structural protein 4B. {ECO:0000250}. FT /FTId=PRO_0000268143. FT CHAIN 2488 3387 RNA-directed RNA polymerase NS5. FT {ECO:0000250}. 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 INTRAMEM 726 746 Helical. {ECO:0000255}. FT TOPO_DOM 747 753 Extracellular. {ECO:0000255}. FT INTRAMEM 754 774 Helical. {ECO:0000255}. FT TOPO_DOM 775 1156 Extracellular. {ECO:0000255}. FT TRANSMEM 1157 1177 Helical. {ECO:0000255}. FT TOPO_DOM 1178 1197 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1198 1218 Helical. {ECO:0000255}. FT TOPO_DOM 1219 1237 Lumenal. {ECO:0000255}. FT TRANSMEM 1238 1258 Helical. {ECO:0000255}. FT TOPO_DOM 1259 1285 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1286 1306 Helical. {ECO:0000255}. FT TOPO_DOM 1307 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:0000255}. FT TOPO_DOM 1367 1369 Lumenal. {ECO:0000255}. FT TRANSMEM 1370 1390 Helical. {ECO:0000255}. FT TOPO_DOM 1391 1437 Cytoplasmic. {ECO:0000255}. FT INTRAMEM 1438 1458 Helical. {ECO:0000255}. 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 2273 Lumenal. {ECO:0000255}. FT INTRAMEM 2274 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 32 73 Hydrophobic; homodimerization of capsid FT protein C. {ECO:0000250}. FT REGION 1397 1436 Interacts with and activates NS3 FT protease. {ECO:0000255|PROSITE- FT ProRule:PRU00859}. FT MOTIF 1758 1761 DEAH box. 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 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:0000255}. FT SITE 113 114 Cleavage; by host signal peptidase. FT {ECO:0000250}. FT SITE 204 205 Cleavage; by host furin. {ECO:0000255}. FT SITE 279 280 Cleavage; by host signal peptidase. FT {ECO:0000255}. FT SITE 774 775 Cleavage; by host signal peptidase. FT {ECO:0000255}. FT SITE 1126 1127 Cleavage; by host. {ECO:0000250}. FT SITE 1344 1345 Cleavage; by viral protease NS3. FT {ECO:0000255}. FT SITE 1474 1475 Cleavage; by autolysis. {ECO:0000255}. FT SITE 2092 2093 Cleavage; by autolysis. {ECO:0000255}. FT SITE 2219 2220 Cleavage; by viral protease NS3. FT {ECO:0000255}. FT SITE 2242 2243 Cleavage; by host signal peptidase. FT {ECO:0000255}. FT SITE 2487 2488 Cleavage; by viral protease NS3. FT {ECO:0000255}. 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 CARBOHYD 182 182 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 346 346 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 432 432 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 981 981 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 2297 2297 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 2301 2301 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT CARBOHYD 2453 2453 N-linked (GlcNAc...); by host. FT {ECO:0000255}. FT DISULFID 282 309 {ECO:0000250}. FT DISULFID 339 400 {ECO:0000250}. FT DISULFID 353 384 {ECO:0000250}. FT DISULFID 371 395 {ECO:0000250}. FT DISULFID 464 564 {ECO:0000250}. FT DISULFID 581 612 {ECO:0000250}. 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 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 //