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 21-MAR-2012, entry version 110. 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 Short=NS2A-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 2 (strain 16681-PDK53) (DENV-2). OC Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; OC 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 MEDLINE=92188532; 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). 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). 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 -!- 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 an 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). 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). CC -!- FUNCTION: Non-structural protein 2A may be involved viral RNA CC replication and capsid assembly (Potential). CC -!- FUNCTION: Non-structural protein 2B is a required cofactor for the CC serine protease function of NS3 (By similarity). 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 -!- 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, functionning as a replication complex. NS4A might also CC regulate the ATPase activity of the NS3 helicase (By similarity). CC -!- FUNCTION: Peptide 2k functions as a signal peptide for NS4B and is CC required for the interferon antagonism activity of the latter (By CC similarity). 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 (By similarity). 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 -!- 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). 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. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + m(7)G(5')pppR-RNA = CC S-adenosyl-L-homocysteine + m(7)G(5')pppRm-RNA. 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). CC -!- SUBCELLULAR LOCATION: Capsid protein C: Virion (Potential). CC -!- SUBCELLULAR LOCATION: Peptide pr: Secreted (By similarity). CC -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane; CC Multi-pass membrane protein (By similarity). Host endoplasmic CC reticulum membrane; Multi-pass membrane protein (By similarity). CC -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane; Multi- CC pass membrane protein (By similarity). Host endoplasmic reticulum CC membrane; Multi-pass membrane protein (By similarity). CC -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted. Host CC endoplasmic reticulum membrane; Peripheral membrane protein; CC Lumenal side (By similarity). CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A-alpha: Host CC endoplasmic reticulum membrane; Multi-pass membrane protein CC (Potential). CC -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic CC reticulum membrane; Multi-pass membrane protein (Potential). CC -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host CC endoplasmic reticulum membrane; Peripheral membrane protein; CC Cytoplasmic side (By similarity). CC -!- SUBCELLULAR LOCATION: Serine protease NS3: Host endoplasmic CC reticulum membrane; Peripheral membrane protein; Cytoplasmic side CC (By similarity). Note=Remains non-covalently associated to NS3 CC protease (By similarity). CC -!- SUBCELLULAR LOCATION: Non-structural protein 4A: Host endoplasmic CC reticulum membrane; Multi-pass membrane protein (By similarity). CC Note=Located in RE-associated vesicles hosting the replication CC complex. CC -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic CC reticulum membrane; Multi-pass membrane protein (By similarity). CC -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host CC endoplasmic reticulum membrane; Peripheral membrane protein; CC Cytoplasmic side (By similarity). Host nucleus (By similarity). CC Note=Located in RE-associated vesicles hosting the replication CC complex. CC -!- DOMAIN: Transmembrane domains of the small envelope protein M and CC envelope protein E contains an endoplasmic reticulum retention CC signals (By similarity). 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). CC -!- PTM: RNA-directed RNA polymerase NS5 is phosphorylated on serines CC residues. This phosphorylation may trigger NS5 nuclear CC localization (By similarity). CC -!- PTM: Envelope protein E and non-structural protein 1 are N- CC glycosylated (By similarity). CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain. CC -!- SIMILARITY: Contains 1 helicase C-terminal domain. CC -!- SIMILARITY: Contains 1 peptidase S7 domain. CC -!- SIMILARITY: Contains 1 RdRp catalytic domain. 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 EMBL; M84727; -; NOT_ANNOTATED_CDS; 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; 21-100, 115-195, 281-674, 1394-1440, 1495-2093, 2498-2759, 2765-3374. 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 to membrane; IEA:UniProtKB-KW. DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:InterPro. 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:EC. DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA: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:0030683; P:evasion by virus of host immune response; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0019079; P:viral genome replication; IEA:InterPro. DR InterPro; IPR011492; DEAD_Flavivir. DR InterPro; IPR000069; Env_glycoprot_M_flavivir. DR InterPro; IPR013756; Flav_glyE_cen_dom_subdom2. DR InterPro; IPR013754; Flav_glyE_dim. DR InterPro; IPR001122; Flavi_capsidC. 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; Flv_glyE_Ig-like. DR InterPro; IPR014412; Gen_Poly_FLV. DR InterPro; IPR011999; GlycoprotE_cen/dimer_Flavivir. DR InterPro; IPR011998; GlycoprotE_cen/dimer_vir. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR009003; Pept_cys/ser_Trypsin-like. DR InterPro; IPR001850; Peptidase_S7. DR InterPro; IPR000208; RNA-dir_pol_flavivirus. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR002877; rRNA_MeTrfase_RrmJ/FtsJ. DR Gene3D; G3DSA:3.30.67.10; Flav_glyE_cen_2; 1. DR Gene3D; G3DSA:2.60.98.10; Flav_glyE_dim; 3. DR Gene3D; G3DSA:2.60.40.350; Flv_glyE_Ig-like; 1. 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; PF00271; Helicase_C; 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; SSF56983; Flavi_glycoprotE; 1. DR SUPFAM; SSF81296; Ig_E-set; 1. DR SUPFAM; SSF50494; Pept_Ser_Cys; 1. DR PROSITE; PS00690; DEAH_ATP_HELICASE; FALSE_NEG. DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1. DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; FALSE_NEG. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Capsid protein; KW 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 Initiation of viral infection; Membrane; Metal-binding; KW Methyltransferase; Multifunctional enzyme; Nucleotide-binding; KW Nucleotidyltransferase; Phosphoprotein; Protease; RNA replication; KW RNA-binding; RNA-directed RNA polymerase; Secreted; Serine protease; KW Transcription; Transcription regulation; Transferase; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; KW Viral envelope protein; Viral immunoevasion; KW Viral penetration into host cytoplasm; Virion; KW Virus endocytosis by host. FT CHAIN 1 3391 Genome polyprotein. FT /FTId=PRO_0000405214. FT CHAIN 1 100 Capsid protein C (By similarity). FT /FTId=PRO_0000037936. FT PROPEP 101 114 ER anchor for the protein C, removed in FT mature form by serine protease NS3 (By FT similarity). FT /FTId=PRO_0000037937. FT CHAIN 115 280 prM (By similarity). FT /FTId=PRO_0000308279. FT CHAIN 115 205 Peptide pr (By similarity). FT /FTId=PRO_0000308280. FT CHAIN 206 280 Small envelope protein M (By similarity). FT /FTId=PRO_0000037938. FT CHAIN 281 775 Envelope protein E (By similarity). FT /FTId=PRO_0000037939. FT CHAIN 776 1127 Non-structural protein 1 (By similarity). FT /FTId=PRO_0000037940. FT CHAIN 1128 1345 Non-structural protein 2A (By FT similarity). FT /FTId=PRO_0000037941. FT CHAIN 1128 1315 Non-structural protein 2A-alpha (By FT similarity). FT /FTId=PRO_0000037942. FT CHAIN 1346 1475 Serine protease subunit NS2B (By FT similarity). FT /FTId=PRO_0000037943. FT CHAIN 1476 2093 Serine protease NS3 (By similarity). FT /FTId=PRO_0000308465. FT CHAIN 2094 2220 Non-structural protein 4A (By FT similarity). FT /FTId=PRO_0000037944. FT PEPTIDE 2221 2243 Peptide 2k (By similarity). FT /FTId=PRO_0000308281. FT CHAIN 2244 2491 Non-structural protein 4B (By FT similarity). FT /FTId=PRO_0000037945. FT CHAIN 2492 3391 RNA-directed RNA polymerase NS5 (By FT similarity). FT /FTId=PRO_0000037946. FT TOPO_DOM 1 101 Cytoplasmic (Potential). FT TRANSMEM 102 122 Helical; (Potential). FT TOPO_DOM 123 242 Extracellular (Potential). FT TRANSMEM 243 260 Helical; (Potential). FT TOPO_DOM 261 261 Cytoplasmic (Potential). FT TRANSMEM 262 280 Helical; (Potential). FT TOPO_DOM 281 727 Extracellular (Potential). FT INTRAMEM 728 746 Helical; (Potential). FT TOPO_DOM 747 752 Extracellular (Potential). FT INTRAMEM 753 773 Helical; (Potential). FT TOPO_DOM 774 1124 Extracellular (Potential). FT TRANSMEM 1125 1145 Helical; (Potential). FT TOPO_DOM 1146 1153 Cytoplasmic (Potential). FT TRANSMEM 1154 1174 Helical; (Potential). FT TOPO_DOM 1175 1184 Lumenal (Potential). FT TRANSMEM 1185 1205 Helical; (Potential). FT TOPO_DOM 1206 1271 Cytoplasmic (Potential). FT TRANSMEM 1272 1292 Helical; (Potential). FT TOPO_DOM 1293 1317 Lumenal (Potential). FT TRANSMEM 1318 1338 Helical; (Potential). FT TOPO_DOM 1339 1346 Cytoplasmic (Potential). FT TRANSMEM 1347 1367 Helical; (Potential). FT TOPO_DOM 1368 1370 Lumenal (Potential). FT TRANSMEM 1371 1391 Helical; (Potential). FT TOPO_DOM 1392 1447 Cytoplasmic (Potential). FT INTRAMEM 1448 1468 Helical; (Potential). FT TOPO_DOM 1469 2147 Cytoplasmic (Potential). FT TRANSMEM 2148 2168 Helical; (Potential). FT TOPO_DOM 2169 2170 Lumenal (Potential). FT INTRAMEM 2171 2191 Helical; (Potential). FT TOPO_DOM 2192 2192 Lumenal (Potential). FT TRANSMEM 2193 2213 Helical; (Potential). FT TOPO_DOM 2214 2228 Cytoplasmic (Potential). FT TRANSMEM 2229 2249 Helical; Note=Signal for NS4B; FT (Potential). FT TOPO_DOM 2250 2277 Lumenal (Potential). FT INTRAMEM 2278 2295 Helical; (Potential). FT TOPO_DOM 2296 2316 Lumenal (Potential). FT INTRAMEM 2317 2337 Helical; (Potential). FT TOPO_DOM 2338 2347 Lumenal (Potential). FT TRANSMEM 2348 2368 Helical; (Potential). FT TOPO_DOM 2369 2413 Cytoplasmic (Potential). FT TRANSMEM 2414 2434 Helical; (Potential). FT TOPO_DOM 2435 2459 Lumenal (Potential). FT TRANSMEM 2460 2480 Helical; (Potential). FT TOPO_DOM 2481 3391 Cytoplasmic (Potential). FT DOMAIN 1476 1653 Peptidase S7. FT DOMAIN 1655 1811 Helicase ATP-binding. FT DOMAIN 1821 1988 Helicase C-terminal. FT DOMAIN 3020 3169 RdRp catalytic. FT NP_BIND 1668 1675 ATP (Potential). FT REGION 33 74 Hydrophobic; homodimerization of capsid FT protein C (By similarity). FT REGION 1398 1437 Interacts with and activates NS3 protease FT (By similarity). FT MOTIF 1759 1762 DEAH box. 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 (By similarity). FT ACT_SITE 1550 1550 Charge relay system; for serine protease FT NS3 activity (By similarity). FT ACT_SITE 1610 1610 Charge relay system; for serine protease FT NS3 activity (By similarity). FT ACT_SITE 2552 2552 For 2'-O-methyltransferase activity (By FT similarity). FT ACT_SITE 2637 2637 For 2'-O-methyltransferase and N-7 FT methyltransferase activity (By FT similarity). FT ACT_SITE 2672 2672 For 2'-O-methyltransferase activity (By FT similarity). FT ACT_SITE 2708 2708 For 2'-O-methyltransferase activity (By FT similarity). FT SITE 100 101 Cleavage; by viral protease NS3 FT (Potential). FT SITE 114 115 Cleavage; by host signal peptidase (By FT similarity). FT SITE 205 206 Cleavage; by host furin (Potential). FT SITE 280 281 Cleavage; by host signal peptidase FT (Potential). FT SITE 775 776 Cleavage; by host signal peptidase FT (Potential). FT SITE 1127 1128 Cleavage; by host (By similarity). FT SITE 1345 1346 Cleavage; by viral protease NS3 FT (Potential). FT SITE 1475 1476 Cleavage; by autolysis (Potential). FT SITE 2093 2094 Cleavage; by autolysis (Potential). FT SITE 2220 2221 Cleavage; by viral protease NS3 FT (Potential). FT SITE 2243 2244 Cleavage; by host signal peptidase FT (Potential). FT SITE 2491 2492 Cleavage; by viral protease NS3 FT (Potential). FT CARBOHYD 183 183 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 347 347 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 433 433 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 905 905 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 982 982 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 2301 2301 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 2305 2305 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 2457 2457 N-linked (GlcNAc...); by host FT (Potential). FT DISULFID 283 310 By similarity. FT DISULFID 340 401 By similarity. FT DISULFID 354 385 By similarity. FT DISULFID 372 396 By similarity. FT DISULFID 465 565 By similarity. FT DISULFID 582 613 By similarity. FT HELIX 2503 2509 FT HELIX 2514 2521 FT STRAND 2525 2528 FT HELIX 2530 2533 FT HELIX 2551 2557 FT TURN 2558 2560 FT STRAND 2568 2571 FT TURN 2579 2581 FT HELIX 2623 2625 FT STRAND 2632 2636 FT HELIX 2645 2648 FT HELIX 2652 2662 FT STRAND 2668 2674 FT HELIX 2680 2691 FT STRAND 2709 2712 FT HELIX 2719 2732 FT HELIX 2733 2735 FT STRAND 2742 2745 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 //