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   28-JUN-2011, entry version 108.
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";
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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: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; IPR014001; DEAD-like_helicase.
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; 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
//