ID   POLG_HCV77              Reviewed;        3011 AA.
AC   P27958; O36579; O36608; O36609; O36610;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 242.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Core protein precursor;
DE     AltName: Full=Capsid protein C;
DE     AltName: Full=p23;
DE   Contains:
DE     RecName: Full=Mature core protein;
DE     AltName: Full=p21;
DE   Contains:
DE     RecName: Full=Envelope glycoprotein E1;
DE     AltName: Full=gp32;
DE     AltName: Full=gp35;
DE   Contains:
DE     RecName: Full=Envelope glycoprotein E2;
DE     AltName: Full=NS1;
DE     AltName: Full=gp68;
DE     AltName: Full=gp70;
DE   Contains:
DE     RecName: Full=Viroporin p7;
DE   Contains:
DE     RecName: Full=Protease NS2;
DE              Short=p23;
DE              EC=3.4.22.- {ECO:0000250|UniProtKB:P26663};
DE     AltName: Full=Non-structural protein 2;
DE              Short=NS2;
DE   Contains:
DE     RecName: Full=Serine protease/helicase NS3;
DE              EC=3.4.21.98 {ECO:0000269|PubMed:8035505, ECO:0000269|PubMed:8386278};
DE              EC=3.6.1.15 {ECO:0000269|PubMed:15269774, ECO:0000269|PubMed:16397502, ECO:0000269|PubMed:25551442};
DE              EC=3.6.4.13 {ECO:0000269|PubMed:15269774, ECO:0000269|PubMed:16397502, ECO:0000269|PubMed:25551442};
DE     AltName: Full=Hepacivirin;
DE     AltName: Full=NS3 helicase {ECO:0000303|PubMed:25551442};
DE     AltName: Full=NS3 protease {ECO:0000303|PubMed:8861917};
DE     AltName: Full=NS3P;
DE     AltName: Full=Viroporin p70;
DE   Contains:
DE     RecName: Full=Non-structural protein 4A;
DE              Short=NS4A;
DE     AltName: Full=p8;
DE   Contains:
DE     RecName: Full=Non-structural protein 4B;
DE              Short=NS4B;
DE     AltName: Full=p27;
DE   Contains:
DE     RecName: Full=Non-structural protein 5A;
DE              Short=NS5A;
DE     AltName: Full=p56/58;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              EC=2.7.7.48 {ECO:0000269|PubMed:20729191};
DE     AltName: Full=NS5B;
DE     AltName: Full=p68;
OS   Hepatitis C virus genotype 1a (isolate H77) (HCV).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC   Amarillovirales; Flaviviridae; Hepacivirus; Hepacivirus hominis;
OC   hepatitis C virus genotype 1a.
OX   NCBI_TaxID=63746;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND DOMAIN (SERINE PROTEASE/HELICASE
RP   NS3).
RX   PubMed=1658800; DOI=10.1073/pnas.88.22.10292;
RA   Inchauspe G., Zebedee S., Lee D.H.H., Sugitani M., Nasoff M., Prince A.M.;
RT   "Genomic structure of the human prototype strain H of hepatitis C virus:
RT   comparison with American and Japanese isolates.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:10292-10296(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate H77;
RX   PubMed=9228008; DOI=10.1126/science.277.5325.570;
RA   Kolykhalov A.A., Agapov E.V., Blight K.J., Mihalik K., Feinstone S.M.,
RA   Rice C.M.;
RT   "Transmission of hepatitis C by intrahepatic inoculation with transcribed
RT   RNA.";
RL   Science 277:570-574(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate H77;
RX   PubMed=9238047; DOI=10.1073/pnas.94.16.8738;
RA   Yanagi M., Purcell R.H., Emerson S.U., Bukh J.;
RT   "Transcripts from a single full-length cDNA clone of hepatitis C virus are
RT   infectious when directly transfected into the liver of a chimpanzee.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:8738-8743(1997).
RN   [4]
RP   PROTEIN SEQUENCE OF 2313-2328, PHOSPHORYLATION AT SER-2321 (NON-STRUCTURAL
RP   PROTEIN 5A), AND MUTAGENESIS OF SER-2321.
RX   PubMed=10488152; DOI=10.1074/jbc.274.39.28011;
RA   Reed K.E., Rice C.M.;
RT   "Identification of the major phosphorylation site of the hepatitis C virus
RT   H strain NS5A protein as serine 2321.";
RL   J. Biol. Chem. 274:28011-28018(1999).
RN   [5]
RP   FUNCTION (PROTEASE NS2), MUTAGENESIS OF HIS-952; CYS-993 AND SER-1165,
RP   ACTIVE SITE (SERINE PROTEASE/HELICASE NS3), AND ACTIVE SITE (PROTEASE NS2).
RX   PubMed=8248148; DOI=10.1073/pnas.90.22.10583;
RA   Grakoui A., McCourt D.W., Wychowski C., Feinstone S.M., Rice C.M.;
RT   "A second hepatitis C virus-encoded proteinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:10583-10587(1993).
RN   [6]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), CATALYTIC ACTIVITY (SERINE
RP   PROTEASE/HELICASE NS3), PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), ACTIVE
RP   SITE (SERINE PROTEASE/HELICASE NS3), AND MUTAGENESIS OF HIS-1083 AND
RP   SER-1165.
RX   PubMed=8386278; DOI=10.1128/jvi.67.5.2832-2843.1993;
RA   Grakoui A., McCourt D.W., Wychowski C., Feinstone S.M., Rice C.M.;
RT   "Characterization of the hepatitis C virus-encoded serine proteinase:
RT   determination of proteinase-dependent polyprotein cleavage sites.";
RL   J. Virol. 67:2832-2843(1993).
RN   [7]
RP   PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX   PubMed=7679746; DOI=10.1128/jvi.67.3.1385-1395.1993;
RA   Grakoui A., Wychowski C., Lin C., Feinstone S.M., Rice C.M.;
RT   "Expression and identification of hepatitis C virus polyprotein cleavage
RT   products.";
RL   J. Virol. 67:1385-1395(1993).
RN   [8]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4A), FUNCTION (SERINE PROTEASE/HELICASE
RP   NS3), AND PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN).
RX   PubMed=8189513; DOI=10.1128/jvi.68.6.3753-3760.1994;
RA   Failla C., Tomei L., De Francesco R.;
RT   "Both NS3 and NS4A are required for proteolytic processing of hepatitis C
RT   virus nonstructural proteins.";
RL   J. Virol. 68:3753-3760(1994).
RN   [9]
RP   PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), CATALYTIC ACTIVITY (SERINE
RP   PROTEASE/HELICASE NS3), AND FUNCTION (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=8035505; DOI=10.1128/jvi.68.8.5045-5055.1994;
RA   Bartenschlager R., Ahlborn-Laake L., Mous J., Jacobsen H.;
RT   "Kinetic and structural analyses of hepatitis C virus polyprotein
RT   processing.";
RL   J. Virol. 68:5045-5055(1994).
RN   [10]
RP   INTERACTION WITH NON-STRUCTURAL PROTEIN 4A (SERINE PROTEASE/HELICASE NS3),
RP   AND INTERACTION WITH SERINE PROTEASE/HELICASE NS3 (NON-STRUCTURAL PROTEIN
RP   4A).
RX   PubMed=7769699; DOI=10.1128/jvi.69.7.4373-4380.1995;
RA   Lin C., Thomson J.A., Rice C.M.;
RT   "A central region in the hepatitis C virus NS4A protein allows formation of
RT   an active NS3-NS4A serine proteinase complex in vivo and in vitro.";
RL   J. Virol. 69:4373-4380(1995).
RN   [11]
RP   INTERACTION WITH ENVELOPE GLYCOPROTEIN E1 (MATURE CORE PROTEIN), AND
RP   INTERACTION WITH MATURE CORE PROTEIN (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=8764026; DOI=10.1128/jvi.70.8.5177-5182.1996;
RA   Lo S.-Y., Selby M.J., Ou J.-H.;
RT   "Interaction between hepatitis C virus core protein and E1 envelope
RT   protein.";
RL   J. Virol. 70:5177-5182(1996).
RN   [12]
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 5A), AND NUCLEAR LOCALIZATION
RP   SIGNAL (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=8982089; DOI=10.1016/s0378-1119(96)00555-0;
RA   Ide Y., Zhang L., Chen M., Inchauspe G., Bahl C., Sasaguri Y.,
RA   Padmanabhan R.;
RT   "Characterization of the nuclear localization signal and subcellular
RT   distribution of hepatitis C virus nonstructural protein NS5A.";
RL   Gene 182:203-211(1996).
RN   [13]
RP   SUBCELLULAR LOCATION (MATURE CORE PROTEIN).
RX   PubMed=9037030; DOI=10.1073/pnas.94.4.1200;
RA   Barba G., Harper F., Harada T., Kohara M., Goulinet S., Matsuura Y.,
RA   Eder G., Schaff Z., Chapman M.J., Miyamura T., Brechot C.;
RT   "Hepatitis C virus core protein shows a cytoplasmic localization and
RT   associates to cellular lipid storage droplets.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:1200-1205(1997).
RN   [14]
RP   GLYCOSYLATION AT ASN-196; ASN-209; ASN-234 AND ASN-305.
RX   PubMed=10211957; DOI=10.1099/0022-1317-80-4-887;
RA   Meunier J.C., Fournillier A., Choukhi A., Cahour A., Cocquerel L.,
RA   Dubuisson J., Wychowski C.;
RT   "Analysis of the glycosylation sites of hepatitis C virus (HCV)
RT   glycoprotein E1 and the influence of E1 glycans on the formation of the HCV
RT   glycoprotein complex.";
RL   J. Gen. Virol. 80:887-896(1999).
RN   [15]
RP   INTERACTION WITH HOST EIF2AK2 (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=10390359; DOI=10.1126/science.285.5424.107;
RA   Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M.C.;
RT   "Inhibition of the interferon-inducible protein kinase PKR by HCV E2
RT   protein.";
RL   Science 285:107-110(1999).
RN   [16]
RP   INTERACTION WITH HOST SRCAP (NON-STRUCTURAL PROTEIN 5A), AND SUBCELLULAR
RP   LOCATION (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=10702287; DOI=10.1074/jbc.275.10.7184;
RA   Ghosh A.K., Majumder M., Steele R., Yaciuk P., Chrivia J., Ray R.,
RA   Ray R.B.;
RT   "Hepatitis C virus NS5A protein modulates transcription through a novel
RT   cellular transcription factor SRCAP.";
RL   J. Biol. Chem. 275:7184-7188(2000).
RN   [17]
RP   SUBCELLULAR LOCATION (ENVELOPE GLYCOPROTEIN E1), AND SUBCELLULAR LOCATION
RP   (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=10729138; DOI=10.1128/jvi.74.8.3623-3633.2000;
RA   Cocquerel L., Wychowski C., Minner F., Penin F., Dubuisson J.;
RT   "Charged residues in the transmembrane domains of hepatitis C virus
RT   glycoproteins play a major role in the processing, subcellular
RT   localization, and assembly of these envelope proteins.";
RL   J. Virol. 74:3623-3633(2000).
RN   [18]
RP   REVIEW.
RX   PubMed=10718937; DOI=10.1046/j.1365-2893.2000.00201.x;
RA   McLauchlan J.;
RT   "Properties of the hepatitis C virus core protein: a structural protein
RT   that modulates cellular processes.";
RL   J. Viral Hepat. 7:2-14(2000).
RN   [19]
RP   FUNCTION (MATURE CORE PROTEIN), AND INTERACTION WITH HOST C1QR1 (MATURE
RP   CORE PROTEIN).
RX   PubMed=11086025; DOI=10.1172/jci10323;
RA   Kittlesen D.J., Chianese-Bullock K.A., Yao Z.Q., Braciale T.J., Hahn Y.S.;
RT   "Interaction between complement receptor gC1qR and hepatitis C virus core
RT   protein inhibits T-lymphocyte proliferation.";
RL   J. Clin. Invest. 106:1239-1249(2000).
RN   [20]
RP   DOMAIN (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=11356980; DOI=10.1128/jvi.75.12.5703-5710.2001;
RA   Penin F., Combet C., Germanidis G., Frainais P.-O., Deleage G.,
RA   Pawlotsky J.-M.;
RT   "Conservation of the conformation and positive charges of hepatitis C virus
RT   E2 envelope glycoprotein hypervariable region 1 points to a role in cell
RT   attachment.";
RL   J. Virol. 75:5703-5710(2001).
RN   [21]
RP   TOPOLOGY (RNA-DIRECTED RNA POLYMERASE), AND SUBCELLULAR LOCATION
RP   (RNA-DIRECTED RNA POLYMERASE).
RX   PubMed=11557752; DOI=10.1074/jbc.m103358200;
RA   Schmidt-Mende J., Bieck E., Huegle T., Penin F., Rice C.M., Blum H.E.,
RA   Moradpour D.;
RT   "Determinants for membrane association of the hepatitis C virus RNA-
RT   dependent RNA polymerase.";
RL   J. Biol. Chem. 276:44052-44063(2001).
RN   [22]
RP   RIBOSOMAL FRAMESHIFT.
RX   PubMed=11447125; DOI=10.1093/emboj/20.14.3840;
RA   Xu Z., Choi J., Yen T.S.B., Lu W., Strohecker A., Govindarajan S.,
RA   Chien D., Selby M.J., Ou J.-H.;
RT   "Synthesis of a novel hepatitis C virus protein by ribosomal frameshift.";
RL   EMBO J. 20:3840-3848(2001).
RN   [23]
RP   DOMAIN (ENVELOPE GLYCOPROTEIN E1), DOMAIN (ENVELOPE GLYCOPROTEIN E2),
RP   INTERACTION WITH ENVELOPE GLYCOPROTEIN E2 (ENVELOPE GLYCOPROTEIN E1), AND
RP   INTERACTION WITH ENVELOPE GLYCOPROTEIN E1 (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=11145889; DOI=10.1006/viro.2000.0693;
RA   Patel J., Patel A.H., McLauchlan J.;
RT   "The transmembrane domain of the hepatitis C virus E2 glycoprotein is
RT   required for correct folding of the E1 glycoprotein and native complex
RT   formation.";
RL   Virology 279:58-68(2001).
RN   [24]
RP   TOPOLOGY (ENVELOPE GLYCOPROTEIN E2), TOPOLOGY (ENVELOPE GLYCOPROTEIN E1),
RP   SUBCELLULAR LOCATION (ENVELOPE GLYCOPROTEIN E2), AND SUBCELLULAR LOCATION
RP   (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=12065403; DOI=10.1093/emboj/cdf295;
RA   Cocquerel L., Op de Beeck A., Lambot M., Roussel J., Delgrange D.,
RA   Pillez A., Wychowski C., Penin F., Dubuisson J.;
RT   "Topological changes in the transmembrane domains of hepatitis C virus
RT   envelope glycoproteins.";
RL   EMBO J. 21:2893-2902(2002).
RN   [25]
RP   TOPOLOGY (VIROPORIN P7), AND SUBCELLULAR LOCATION (VIROPORIN P7).
RX   PubMed=11907211; DOI=10.1128/jvi.76.8.3720-3730.2002;
RA   Carrere-Kremer S., Montpellier-Pala C., Cocquerel L., Wychowski C.,
RA   Penin F., Dubuisson J.;
RT   "Subcellular localization and topology of the p7 polypeptide of hepatitis C
RT   virus.";
RL   J. Virol. 76:3720-3730(2002).
RN   [26]
RP   SUBCELLULAR LOCATION (MATURE CORE PROTEIN).
RX   PubMed=11706032; DOI=10.1074/jbc.m108798200;
RA   Hope R.G., Murphy D.J., McLauchlan J.;
RT   "The domains required to direct core proteins of hepatitis C virus and GB
RT   virus-B to lipid droplets share common features with plant oleosin
RT   proteins.";
RL   J. Biol. Chem. 277:4261-4270(2002).
RN   [27]
RP   TOPOLOGY (NON-STRUCTURAL PROTEIN 5A), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=11744739; DOI=10.1074/jbc.m111289200;
RA   Brass V., Bieck E., Montserret R., Woelk B., Hellings J.A., Blum H.E.,
RA   Penin F., Moradpour D.;
RT   "An amino-terminal amphipathic alpha-helix mediates membrane association of
RT   the hepatitis C virus nonstructural protein 5A.";
RL   J. Biol. Chem. 277:8130-8139(2002).
RN   [28]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4B), AND REPLICATION COMPLEX.
RX   PubMed=12021330; DOI=10.1128/jvi.76.12.5974-5984.2002;
RA   Egger D., Woelk B., Gosert R., Bianchi L., Blum H.E., Moradpour D.,
RA   Bienz K.;
RT   "Expression of hepatitis C virus proteins induces distinct membrane
RT   alterations including a candidate viral replication complex.";
RL   J. Virol. 76:5974-5984(2002).
RN   [29]
RP   INTERACTION WITH RNA-DIRECTED RNA POLYMERASE (NON-STRUCTURAL PROTEIN 5A),
RP   AND INTERACTION WITH NON-STRUCTURAL PROTEIN 5A (RNA-DIRECTED RNA
RP   POLYMERASE).
RX   PubMed=11801599; DOI=10.1074/jbc.m111392200;
RA   Shirota Y., Luo H., Qin W., Kaneko S., Yamashita T., Kobayashi K.,
RA   Murakami S.;
RT   "Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP)
RT   NS5B and modulates RNA-dependent RNA polymerase activity.";
RL   J. Biol. Chem. 277:11149-11155(2002).
RN   [30]
RP   INTERACTION WITH HOST CD81 AND SCARB1 (ENVELOPE GLYCOPROTEIN E2), FUNCTION
RP   (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=12356718; DOI=10.1093/emboj/cdf529;
RA   Scarselli E., Ansuini H., Cerino R., Roccasecca R.M., Acali S.,
RA   Filocamo G., Traboni C., Nicosia A., Cortese R., Vitelli A.;
RT   "The human scavenger receptor class B type I is a novel candidate receptor
RT   for the hepatitis C virus.";
RL   EMBO J. 21:5017-5025(2002).
RN   [31]
RP   INTERACTION WITH HOST CD81 (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE
RP   GLYCOPROTEIN E1), AND FUNCTION (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=12970454; DOI=10.1128/jvi.77.19.10677-10683.2003;
RA   Cocquerel L., Kuo C.-C., Dubuisson J., Levy S.;
RT   "CD81-dependent binding of hepatitis C virus E1E2 heterodimers.";
RL   J. Virol. 77:10677-10683(2003).
RN   [32]
RP   INTERACTION WITH HOST CD81 (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE
RP   GLYCOPROTEIN E1), AND FUNCTION (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=12913001; DOI=10.1074/jbc.m305289200;
RA   Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S.,
RA   Scarselli E., Cortese R., Nicosia A., Cosset F.-L.;
RT   "Cell entry of hepatitis C virus requires a set of co-receptors that
RT   include the CD81 tetraspanin and the SR-B1 scavenger receptor.";
RL   J. Biol. Chem. 278:41624-41630(2003).
RN   [33]
RP   REPLICATION COMPLEX.
RX   PubMed=12692249; DOI=10.1128/jvi.77.9.5487-5492.2003;
RA   Gosert R., Egger D., Lohmann V., Bartenschlager R., Blum H.E., Bienz K.,
RA   Moradpour D.;
RT   "Identification of the hepatitis C virus RNA replication complex in Huh-7
RT   cells harboring subgenomic replicons.";
RL   J. Virol. 77:5487-5492(2003).
RN   [34]
RP   SUBUNIT (VIROPORIN P7), AND FUNCTION (VIROPORIN P7).
RX   PubMed=12560074; DOI=10.1016/s0014-5793(02)03851-6;
RA   Griffin S.D., Beales L.P., Clarke D.S., Worsfold O., Evans S.D., Jaeger J.,
RA   Harris M.P., Rowlands D.J.;
RT   "The p7 protein of hepatitis C virus forms an ion channel that is blocked
RT   by the antiviral drug, Amantadine.";
RL   FEBS Lett. 535:34-38(2003).
RN   [35]
RP   FUNCTION (VIROPORIN P7).
RX   PubMed=12719519; DOI=10.1073/pnas.1031527100;
RA   Pavlovic D., Neville D.C., Argaud O., Blumberg B., Dwek R.A., Fischer W.B.,
RA   Zitzmann N.;
RT   "The hepatitis C virus p7 protein forms an ion channel that is inhibited by
RT   long-alkyl-chain iminosugar derivatives.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:6104-6108(2003).
RN   [36]
RP   MUTAGENESIS OF LYS-779 AND ARG-781.
RC   STRAIN=Isolate H77;
RX   PubMed=14504405; DOI=10.1073/pnas.1834545100;
RA   Sakai A., Claire M.S., Faulk K., Govindarajan S., Emerson S.U.,
RA   Purcell R.H., Bukh J.;
RT   "The p7 polypeptide of hepatitis C virus is critical for infectivity and
RT   contains functionally important genotype-specific sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:11646-11651(2003).
RN   [37]
RP   REPLICATION COMPLEX.
RX   PubMed=12692242; DOI=10.1128/jvi.77.9.5401-5414.2003;
RA   Dimitrova M., Imbert I., Kieny M.P., Schuster C.;
RT   "Protein-protein interactions between hepatitis C virus nonstructural
RT   proteins.";
RL   J. Virol. 77:5401-5414(2003).
RN   [38]
RP   TOPOLOGY (NON-STRUCTURAL PROTEIN 4B), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 4B).
RC   STRAIN=Isolate H77;
RX   PubMed=12692244; DOI=10.1128/jvi.77.9.5428-5438.2003;
RA   Lundin M., Monne M., Widell A., Von Heijne G., Persson M.A.A.;
RT   "Topology of the membrane-associated hepatitis C virus protein NS4B.";
RL   J. Virol. 77:5428-5438(2003).
RN   [39]
RP   FUNCTION (MATURE CORE PROTEIN).
RX   PubMed=14602201; DOI=10.1016/j.virusres.2003.08.004;
RA   Ruggieri A., Murdolo M., Rapicetta M.;
RT   "Induction of FAS ligand expression in a human hepatoblastoma cell line by
RT   HCV core protein.";
RL   Virus Res. 97:103-110(2003).
RN   [40]
RP   ACTIVITY REGULATION (RNA-DIRECTED RNA POLYMERASE), PHOSPHORYLATION
RP   (RNA-DIRECTED RNA POLYMERASE), AND INTERACTION WITH HOST PRK2/PKN2
RP   (RNA-DIRECTED RNA POLYMERASE).
RX   PubMed=15364941; DOI=10.1074/jbc.m408617200;
RA   Kim S.J., Kim J.H., Kim Y.G., Lim H.S., Oh J.W.;
RT   "Protein kinase C-related kinase 2 regulates hepatitis C virus RNA
RT   polymerase function by phosphorylation.";
RL   J. Biol. Chem. 279:50031-50041(2004).
RN   [41]
RP   REVIEW.
RX   PubMed=14752815; DOI=10.1002/hep.20032;
RA   Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M.;
RT   "Structural biology of hepatitis C virus.";
RL   Hepatology 39:5-19(2004).
RN   [42]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E1), FUNCTION (ENVELOPE GLYCOPROTEIN E2),
RP   SUBUNIT (ENVELOPE GLYCOPROTEIN E1), SUBUNIT (ENVELOPE GLYCOPROTEIN E2),
RP   GLYCOSYLATION (ENVELOPE GLYCOPROTEIN E1), AND GLYCOSYLATION (ENVELOPE
RP   GLYCOPROTEIN E2).
RX   PubMed=14990718; DOI=10.1128/jvi.78.6.2994-3002.2004;
RA   Op De Beeck A., Voisset C., Bartosch B., Ciczora Y., Cocquerel L., Keck Z.,
RA   Foung S., Cosset F.-L., Dubuisson J.;
RT   "Characterization of functional hepatitis C virus envelope glycoproteins.";
RL   J. Virol. 78:2994-3002(2004).
RN   [43]
RP   FUNCTION (VIROPORIN P7).
RX   PubMed=14741348; DOI=10.1016/s0014-5793(03)01453-4;
RA   Premkumar A., Wilson L., Ewart G.D., Gage P.W.;
RT   "Cation-selective ion channels formed by p7 of hepatitis C virus are
RT   blocked by hexamethylene amiloride.";
RL   FEBS Lett. 557:99-103(2004).
RN   [44]
RP   PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX   PubMed=15247249; DOI=10.1074/jbc.m406315200;
RA   Carrere-Kremer S., Montpellier C., Lorenzo L., Brulin B., Cocquerel L.,
RA   Belouzard S., Penin F., Dubuisson J.;
RT   "Regulation of hepatitis C virus polyprotein processing by signal peptidase
RT   involves structural determinants at the p7 sequence junctions.";
RL   J. Biol. Chem. 279:41384-41392(2004).
RN   [45]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND INTERACTION WITH HOST
RP   CD209/DC-SIGN AND CLEC4M/DC-SIGNR (ENVELOPE GLYCOPROTEIN E2).
RC   STRAIN=Isolate H77;
RX   PubMed=15371595; DOI=10.1073/pnas.0405695101;
RA   Cormier E.G., Durso R.J., Tsamis F., Boussemart L., Manix C., Olson W.C.,
RA   Gardner J.P., Dragic T.;
RT   "L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells
RT   by hepatitis C virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:14067-14072(2004).
RN   [46]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), AND CATALYTIC ACTIVITY (SERINE
RP   PROTEASE/HELICASE NS3).
RX   PubMed=15269774; DOI=10.1038/nature02704;
RA   Serebrov V., Pyle A.M.;
RT   "Periodic cycles of RNA unwinding and pausing by hepatitis C virus NS3
RT   helicase.";
RL   Nature 430:476-480(2004).
RN   [47]
RP   INTERACTION WITH HOST VAPB.
RX   PubMed=16227268; DOI=10.1128/jvi.79.21.13473-13482.2005;
RA   Hamamoto I., Nishimura Y., Okamoto T., Aizaki H., Liu M., Mori Y., Abe T.,
RA   Suzuki T., Lai M.M., Miyamura T., Moriishi K., Matsuura Y.;
RT   "Human VAP-B is involved in hepatitis C virus replication through
RT   interaction with NS5A and NS5B.";
RL   J. Virol. 79:13473-13482(2005).
RN   [48]
RP   PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), TOPOLOGY (VIROPORIN P7), AND
RP   MUTAGENESIS OF VAL-720.
RX   PubMed=15722527; DOI=10.1099/vir.0.80737-0;
RA   Isherwood B.J., Patel A.H.;
RT   "Analysis of the processing and transmembrane topology of the E2p7 protein
RT   of hepatitis C virus.";
RL   J. Gen. Virol. 86:667-676(2005).
RN   [49]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), AND INTERACTION WITH HOST MAVS
RP   (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=16301520; DOI=10.1073/pnas.0508531102;
RA   Li X.D., Sun L., Seth R.B., Pineda G., Chen Z.J.;
RT   "Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral
RT   signaling protein off the mitochondria to evade innate immunity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:17717-17722(2005).
RN   [50]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), AND INTERACTION WITH HOST MAVS
RP   (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=16177806; DOI=10.1038/nature04193;
RA   Meylan E., Curran J., Hofmann K., Moradpour D., Binder M.,
RA   Bartenschlager R., Tschopp J.;
RT   "Cardif is an adaptor protein in the RIG-I antiviral pathway and is
RT   targeted by hepatitis C virus.";
RL   Nature 437:1167-1172(2005).
RN   [51]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), AND INTERACTION WITH HOST TICAM1
RP   (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=15710891; DOI=10.1073/pnas.0408824102;
RA   Li K., Foy E., Ferreon J.C., Nakamura M., Ferreon A.C., Ikeda M., Ray S.C.,
RA   Gale M. Jr., Lemon S.M.;
RT   "Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of
RT   the Toll-like receptor 3 adaptor protein TRIF.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:2992-2997(2005).
RN   [52]
RP   CATALYTIC ACTIVITY (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=16397502; DOI=10.1038/nature04331;
RA   Dumont S., Cheng W., Serebrov V., Beran R.K., Tinoco I. Jr., Pyle A.M.,
RA   Bustamante C.;
RT   "RNA translocation and unwinding mechanism of HCV NS3 helicase and its
RT   coordination by ATP.";
RL   Nature 439:105-108(2006).
RN   [53]
RP   DOMAIN (NON-STRUCTURAL PROTEIN 5A), INTERACTION WITH HOST BIN1
RP   (NON-STRUCTURAL PROTEIN 5A), AND FUNCTION (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=16530520; DOI=10.1053/j.gastro.2005.12.030;
RA   Nanda S.K., Herion D., Liang T.J.;
RT   "The SH3 binding motif of HCV NS5A protein interacts with Bin1 and is
RT   important for apoptosis and infectivity.";
RL   Gastroenterology 130:794-809(2006).
RN   [54]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4B), PALMITOYLATION AT CYS-1968 AND
RP   CYS-1972 (NON-STRUCTURAL PROTEIN 4B), AND MUTAGENESIS OF CYS-1968 AND
RP   CYS-1972.
RC   STRAIN=Isolate H77;
RX   PubMed=16731940; DOI=10.1128/jvi.00053-06;
RA   Yu G.-Y., Lee K.-J., Gao L., Lai M.M.C.;
RT   "Palmitoylation and polymerization or in protein-protein interactions of
RT   hepatitis C virus NS4B protein.";
RL   J. Virol. 80:6013-6023(2006).
RN   [55]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E1), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E2).
RC   STRAIN=Isolate H77;
RX   PubMed=16894197; DOI=10.1099/vir.0.81710-0;
RA   Codran A., Royer C., Jaeck D., Bastien-Valle M., Baumert T.F., Kieny M.P.,
RA   Pereira C.A., Martin J.P.;
RT   "Entry of hepatitis C virus pseudotypes into primary human hepatocytes by
RT   clathrin-dependent endocytosis.";
RL   J. Gen. Virol. 87:2583-2593(2006).
RN   [56]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E1), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E2).
RC   STRAIN=Isolate H77;
RX   PubMed=16533059; DOI=10.1021/bi0523963;
RA   Perez-Berna A.J., Moreno M.R., Guillen J., Bernabeu A., Villalain J.;
RT   "The membrane-active regions of the hepatitis C virus E1 and E2 envelope
RT   glycoproteins.";
RL   Biochemistry 45:3755-3768(2006).
RN   [57]
RP   TOPOLOGY (NON-STRUCTURAL PROTEIN 4B), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 4B).
RC   STRAIN=Isolate H77;
RX   PubMed=17030859; DOI=10.1099/vir.0.82211-0;
RA   Lundin M., Lindstrom H., Groenwall C., Persson M.A.;
RT   "Dual topology of the processed hepatitis C virus protein NS4B is
RT   influenced by the NS5A protein.";
RL   J. Gen. Virol. 87:3263-3272(2006).
RN   [58]
RP   INTERACTION WITH HOST EIF2AK2/PKR (NON-STRUCTURAL PROTEIN 5A), AND FUNCTION
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=16951545;
RA   Liang Y., Kang C.B., Yoon H.S.;
RT   "Molecular and structural characterization of the domain 2 of hepatitis C
RT   virus non-structural protein 5A.";
RL   Mol. Cells 22:13-20(2006).
RN   [59]
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=17192310; DOI=10.1128/jvi.01279-06;
RA   Brass V., Pal Z., Sapay N., Deleage G., Blum H.E., Penin F., Moradpour D.;
RT   "Conserved determinants for membrane association of nonstructural protein
RT   5A from hepatitis C virus and related viruses.";
RL   J. Virol. 81:2745-2757(2007).
RN   [60]
RP   INTERACTION WITH HNRNPA1 AND SEPT6 (RNA-DIRECTED RNA POLYMERASE), AND
RP   SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE).
RX   PubMed=17229681; DOI=10.1128/jvi.01311-06;
RA   Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.;
RT   "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6,
RT   facilitate hepatitis C virus replication.";
RL   J. Virol. 81:3852-3865(2007).
RN   [61]
RP   FUNCTION (MATURE CORE PROTEIN).
RX   PubMed=17881511; DOI=10.1189/jlb.0507268;
RA   Waggoner S.N., Hall C.H., Hahn Y.S.;
RT   "HCV core protein interaction with gC1q receptor inhibits Th1
RT   differentiation of CD4+ T cells via suppression of dendritic cell IL-12
RT   production.";
RL   J. Leukoc. Biol. 82:1407-1419(2007).
RN   [62]
RP   GLYCOSYLATION AT ASN-417; ASN-423; ASN-430; ASN-448; ASN-476; ASN-532;
RP   ASN-540; ASN-556; ASN-576; ASN-623 AND ASN-645, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=18187336; DOI=10.1016/j.jasms.2007.11.022;
RA   Iacob R.E., Perdivara I., Przybylski M., Tomer K.B.;
RT   "Mass spectrometric characterization of glycosylation of hepatitis C virus
RT   E2 envelope glycoprotein reveals extended microheterogeneity of N-
RT   glycans.";
RL   J. Am. Soc. Mass Spectrom. 19:428-444(2008).
RN   [63]
RP   FUNCTION (MATURE CORE PROTEIN), RNA-BINDING (MATURE CORE PROTEIN), AND
RP   DOMAIN (MATURE CORE PROTEIN).
RX   PubMed=18033802; DOI=10.1093/nar/gkm1051;
RA   Ivanyi-Nagy R., Lavergne J.P., Gabus C., Ficheux D., Darlix J.L.;
RT   "RNA chaperoning and intrinsic disorder in the core proteins of
RT   Flaviviridae.";
RL   Nucleic Acids Res. 36:712-725(2008).
RN   [64]
RP   INTERACTION WITH HOST ACY3 (MATURE CORE PROTEIN).
RX   PubMed=19486448; DOI=10.1111/j.1440-1746.2009.05846.x;
RA   Chen Y.R., Chen T.Y., Zhang S.L., Lin S.M., Zhao Y.R., Ye F., Zhang X.,
RA   Shi L., Dang S.S., Liu M.;
RT   "Identification of a novel protein binding to hepatitis C virus core
RT   protein.";
RL   J. Gastroenterol. Hepatol. 24:1300-1304(2009).
RN   [65]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=19182773; DOI=10.1038/nature07684;
RA   Ploss A., Evans M.J., Gaysinskaya V.A., Panis M., You H., de Jong Y.P.,
RA   Rice C.M.;
RT   "Human occludin is a hepatitis C virus entry factor required for infection
RT   of mouse cells.";
RL   Nature 457:882-886(2009).
RN   [66]
RP   DOMAIN (MATURE CORE PROTEIN).
RX   PubMed=18992225; DOI=10.1016/j.bbrc.2008.10.141;
RA   Duvignaud J.B., Savard C., Fromentin R., Majeau N., Leclerc D., Gagne S.M.;
RT   "Structure and dynamics of the N-terminal half of hepatitis C virus core
RT   protein: an intrinsically unstructured protein.";
RL   Biochem. Biophys. Res. Commun. 378:27-31(2009).
RN   [67]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=20375010; DOI=10.1074/jbc.m110.104836;
RA   Harris H.J., Davis C., Mullins J.G., Hu K., Goodall M., Farquhar M.J.,
RA   Mee C.J., McCaffrey K., Young S., Drummer H., Balfe P., McKeating J.A.;
RT   "Claudin association with CD81 defines hepatitis C virus entry.";
RL   J. Biol. Chem. 285:21092-21102(2010).
RN   [68]
RP   FUNCTION (VIROPORIN P7).
RX   PubMed=20824094; DOI=10.1371/journal.ppat.1001087;
RA   Wozniak A.L., Griffin S., Rowlands D., Harris M., Yi M., Lemon S.M.,
RA   Weinman S.A.;
RT   "Intracellular proton conductance of the hepatitis C virus p7 protein and
RT   its contribution to infectious virus production.";
RL   PLoS Pathog. 6:E1001087-E1001087(2010).
RN   [69]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 5A), RNA-BINDING (NON-STRUCTURAL PROTEIN
RP   5A), SUBUNIT (NON-STRUCTURAL PROTEIN 5A), AND DOMAIN (NON-STRUCTURAL
RP   PROTEIN 5A).
RX   PubMed=20926572; DOI=10.1128/jvi.01319-10;
RA   Hwang J., Huang L., Cordek D.G., Vaughan R., Reynolds S.L., Kihara G.,
RA   Raney K.D., Kao C.C., Cameron C.E.;
RT   "Hepatitis C virus nonstructural protein 5A: biochemical characterization
RT   of a novel structural class of RNA-binding proteins.";
RL   J. Virol. 84:12480-12491(2010).
RN   [70]
RP   FUNCTION (PROTEASE NS2), INTERACTION WITH ENVELOPE GLYCOPROTEIN E1
RP   (PROTEASE NS2), INTERACTION WITH ENVELOPE GLYCOPROTEIN E2 (PROTEASE NS2),
RP   INTERACTION WITH PROTEASE NS2 (ENVELOPE GLYCOPROTEIN E1), INTERACTION WITH
RP   PROTEASE NS2 (ENVELOPE GLYCOPROTEIN E2), INTERACTION WITH SERINE
RP   PROTEASE/HELICASE NS3 (PROTEASE NS2), AND INTERACTION WITH PROTEASE NS2
RP   (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=21147927; DOI=10.1128/jvi.02268-10;
RA   Stapleford K.A., Lindenbach B.D.;
RT   "Hepatitis C virus NS2 coordinates virus particle assembly through physical
RT   interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes.";
RL   J. Virol. 85:1706-1717(2011).
RN   [71]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3).
RX   PubMed=21940894; DOI=10.1126/science.1206023;
RA   Cheng W., Arunajadai S.G., Moffitt J.R., Tinoco I. Jr., Bustamante C.;
RT   "Single-base pair unwinding and asynchronous RNA release by the hepatitis C
RT   virus NS3 helicase.";
RL   Science 333:1746-1749(2011).
RN   [72]
RP   DOMAIN (NON-STRUCTURAL PROTEIN 5A), AND INTERACTION WITH HOST VAPB
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=22720086; DOI=10.1371/journal.pone.0039261;
RA   Gupta G., Qin H., Song J.;
RT   "Intrinsically unstructured domain 3 of hepatitis C Virus NS5A forms a
RT   'fuzzy complex' with VAPB-MSP domain which carries ALS-causing mutations.";
RL   PLoS ONE 7:e39261-e39261(2012).
RN   [73]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE GLYCOPROTEIN E1),
RP   MUTAGENESIS OF LEU-399, AND DOMAIN (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=22767607; DOI=10.1074/jbc.m112.365924;
RA   Dao Thi V.L., Granier C., Zeisel M.B., Guerin M., Mancip J., Granio O.,
RA   Penin F., Lavillette D., Bartenschlager R., Baumert T.F., Cosset F.L.,
RA   Dreux M.;
RT   "Characterization of hepatitis C virus particle subpopulations reveals
RT   multiple usage of the scavenger receptor BI for entry steps.";
RL   J. Biol. Chem. 287:31242-31257(2012).
RN   [74]
RP   DISULFIDE BOND (ENVELOPE GLYCOPROTEIN E2), AND MUTAGENESIS OF CYS-429;
RP   CYS-452; CYS-459; CYS-503; CYS-508; CYS-552; CYS-564; CYS-569; CYS-581;
RP   CYS-585; CYS-597; CYS-607; CYS-620; CYS-644; CYS-652 AND CYS-677.
RX   PubMed=22278231; DOI=10.1128/jvi.05396-11;
RA   McCaffrey K., Boo I., Tewierek K., Edmunds M.L., Poumbourios P.,
RA   Drummer H.E.;
RT   "Role of conserved cysteine residues in hepatitis C virus glycoprotein e2
RT   folding and function.";
RL   J. Virol. 86:3961-3974(2012).
RN   [75]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=22855500; DOI=10.1128/jvi.00750-12;
RA   Diao J., Pantua H., Ngu H., Komuves L., Diehl L., Schaefer G.,
RA   Kapadia S.B.;
RT   "Hepatitis C virus induces epidermal growth factor receptor activation via
RT   CD81 binding for viral internalization and entry.";
RL   J. Virol. 86:10935-10949(2012).
RN   [76]
RP   SUBUNIT (NON-STRUCTURAL PROTEIN 4B), INTERACTION WITH NON-STRUCTURAL
RP   PROTEIN 5A (NON-STRUCTURAL PROTEIN 4B), AND INTERACTION WITH NON-STRUCTURAL
RP   PROTEIN 4B (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=23868571; DOI=10.1007/s11262-013-0956-5;
RA   Choi M., Lee S., Choi T., Lee C.;
RT   "A hepatitis C virus NS4B inhibitor suppresses viral genome replication by
RT   disrupting NS4B's dimerization/multimerization as well as its interaction
RT   with NS5A.";
RL   Virus Genes 47:395-407(2013).
RN   [77]
RP   FUNCTION (VIROPORIN P7).
RX   PubMed=24006444; DOI=10.1128/jvi.01962-13;
RA   Shrivastava S., Mukherjee A., Ray R., Ray R.B.;
RT   "Hepatitis C virus induces interleukin-1beta (IL-1beta)/IL-18 in
RT   circulatory and resident liver macrophages.";
RL   J. Virol. 87:12284-12290(2013).
RN   [78]
RP   INTERACTION WITH HOST STING (NON-STRUCTURAL PROTEIN 4B), AND FUNCTION
RP   (NON-STRUCTURAL PROTEIN 4B).
RX   PubMed=23542348; DOI=10.1016/j.jhep.2013.03.019;
RA   Ding Q., Cao X., Lu J., Huang B., Liu Y.J., Kato N., Shu H.B., Zhong J.;
RT   "Hepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade
RT   host innate immunity.";
RL   J. Hepatol. 59:52-58(2013).
RN   [79]
RP   FUNCTION (MATURE CORE PROTEIN), AND INTERACTION WITH HOST STAT1 (MATURE
RP   CORE PROTEIN).
RX   PubMed=23799612; DOI=10.3892/mmr.2013.1541;
RA   Anjum S., Afzal M.S., Ahmad T., Aslam B., Waheed Y., Shafi T., Qadri I.;
RT   "Mutations in the STAT1-interacting domain of the hepatitis C virus core
RT   protein modulate the response to antiviral therapy.";
RL   Mol. Med. Report. 8:487-492(2013).
RN   [80]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=24838241; DOI=10.1074/jbc.m113.538256;
RA   Boyer A., Dumans A., Beaumont E., Etienne L., Roingeard P., Meunier J.C.;
RT   "The association of hepatitis C virus glycoproteins with apolipoproteins E
RT   and B early in assembly is conserved in lipoviral particles.";
RL   J. Biol. Chem. 289:18904-18913(2014).
RN   [81]
RP   INTERACTION WITH HOST CLDN1 (ENVELOPE GLYCOPROTEIN E1), INTERACTION WITH
RP   HOST CLDN1 (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE GLYCOPROTEIN E2),
RP   AND FUNCTION (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=24038151; DOI=10.1002/hep.26733;
RA   Douam F., Dao Thi V.L., Maurin G., Fresquet J., Mompelat D., Zeisel M.B.,
RA   Baumert T.F., Cosset F.L., Lavillette D.;
RT   "Critical interaction between E1 and E2 glycoproteins determines binding
RT   and fusion properties of hepatitis C virus during cell entry.";
RL   Hepatology 59:776-788(2014).
RN   [82]
RP   FUNCTION (SERINE PROTEASE/HELICASE NS3), AND CATALYTIC ACTIVITY (SERINE
RP   PROTEASE/HELICASE NS3).
RX   PubMed=25551442; DOI=10.1371/journal.pone.0115941;
RA   Ventura G.T., Costa E.C., Capaccia A.M., Mohana-Borges R.;
RT   "pH-dependent conformational changes in the HCV NS3 protein modulate its
RT   ATPase and helicase activities.";
RL   PLoS ONE 9:E115941-E115941(2014).
RN   [83]
RP   INTERACTION WITH HOST APOE (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE
RP   GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=25122793; DOI=10.1128/jvi.01660-14;
RA   Lee J.Y., Acosta E.G., Stoeck I.K., Long G., Hiet M.S., Mueller B.,
RA   Fackler O.T., Kallis S., Bartenschlager R.;
RT   "Apolipoprotein E likely contributes to a maturation step of infectious
RT   hepatitis C virus particles and interacts with viral envelope
RT   glycoproteins.";
RL   J. Virol. 88:12422-12437(2014).
RN   [84]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=24698129; DOI=10.1111/febs.12802;
RA   Tello D., Rodriguez-Rodriguez M., Ortega S., Lombana L., Yelamos B.,
RA   Gomez-Gutierrez J., Peterson D.L., Gavilanes F.;
RT   "Fusogenic properties of the ectodomains of hepatitis C virus envelope
RT   proteins.";
RL   FEBS J. 281:2558-2569(2014).
RN   [85]
RP   DOMAIN (MATURE CORE PROTEIN).
RX   PubMed=25424537; DOI=10.1002/pro.2608;
RA   Dolan P.T., Roth A.P., Xue B., Sun R., Dunker A.K., Uversky V.N.,
RA   LaCount D.J.;
RT   "Intrinsic disorder mediates hepatitis C virus core-host cell protein
RT   interactions.";
RL   Protein Sci. 24:221-235(2015).
RN   [86]
RP   INTERACTION WITH HOST METTL7A (NON-STRUCTURAL PROTEIN 4B), AND SUBCELLULAR
RP   LOCATION (NON-STRUCTURAL PROTEIN 4B).
RX   PubMed=26185986; DOI=10.1371/journal.pone.0132839;
RA   Park E.M., Lim Y.S., Ahn B.Y., Hwang S.B.;
RT   "AAM-B Interacts with Nonstructural 4B and Regulates Hepatitis C Virus
RT   Propagation.";
RL   PLoS ONE 10:e0132839-e0132839(2015).
RN   [87]
RP   DOMAIN (NON-STRUCTURAL PROTEIN 5A), INTERACTION WITH HOST PPIA,
RP   RNA-BINDING, AND INTERACTION WITH RNA-DIRECTED RNA POLYMERASE.
RX   PubMed=27676132; DOI=10.1021/acsinfecdis.6b00143;
RA   Ngure M., Issur M., Shkriabai N., Liu H.W., Cosa G., Kvaratskhelia M.,
RA   Goette M.;
RT   "Interactions of the Disordered Domain II of Hepatitis C Virus NS5A with
RT   Cyclophilin A, NS5B, and Viral RNA Show Extensive Overlap.";
RL   ACS Infect. Dis. 2:839-851(2016).
RN   [88]
RP   DOMAIN (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=26727512; DOI=10.1371/journal.ppat.1005376;
RA   Zayas M., Long G., Madan V., Bartenschlager R.;
RT   "Coordination of Hepatitis C Virus Assembly by Distinct Regulatory Regions
RT   in Nonstructural Protein 5A.";
RL   PLoS Pathog. 12:e1005376-e1005376(2016).
RN   [89]
RP   SUBUNIT (MATURE CORE PROTEIN), AND INDUCTION (MATURE CORE PROTEIN).
RX   PubMed=25351725; DOI=10.1099/vir.0.070433-0;
RA   Afzal M.S., Alsaleh K., Farhat R., Belouzard S., Danneels A., Descamps V.,
RA   Duverlie G., Wychowski C., Zaidi N., Dubuisson J., Rouille Y.;
RT   "Regulation of core expression during the hepatitis C virus life cycle.";
RL   J. Gen. Virol. 96:311-321(2015).
RN   [90]
RP   INTERACTION WITH HOST CIDEB (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=27282740; DOI=10.1038/srep27778;
RA   Cai H., Yao W., Li L., Li X., Hu L., Mai R., Peng T.;
RT   "Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of
RT   Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A.";
RL   Sci. Rep. 6:27778-27778(2016).
RN   [91]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 5A), AND UBIQUITINATION (NON-STRUCTURAL
RP   PROTEIN 5A).
RX   PubMed=25683609; DOI=10.1038/cmi.2014.131;
RA   Yang C., Zhao X., Sun D., Yang L., Chong C., Pan Y., Chi X., Gao Y.,
RA   Wang M., Shi X., Sun H., Lv J., Gao Y., Zhong J., Niu J., Sun B.;
RT   "Interferon alpha (IFNalpha)-induced TRIM22 interrupts HCV replication by
RT   ubiquitinating NS5A.";
RL   Cell. Mol. Immunol. 13:94-102(2016).
RN   [92]
RP   FUNCTION (VIROPORIN P7), AND SUBCELLULAR LOCATION (VIROPORIN P7).
RX   PubMed=27320856; DOI=10.1016/j.bbalip.2016.06.011;
RA   Lee G.Y., Lee S., Lee H.R., Yoo Y.D.;
RT   "Hepatitis C virus p7 mediates membrane-to-membrane adhesion.";
RL   Biochim. Biophys. Acta 1861:1096-1101(2016).
RN   [93]
RP   INTERACTION WITH HOST IFI27 (NON-STRUCTURAL PROTEIN 5A), INTERACTION WITH
RP   HOST SKP2 (NON-STRUCTURAL PROTEIN 5A), UBIQUITINATION AT LYS-2350
RP   (NON-STRUCTURAL PROTEIN 5A), AND DOMAIN (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=27194766; DOI=10.1128/jvi.00352-16;
RA   Xue B., Yang D., Wang J., Xu Y., Wang X., Qin Y., Tian R., Chen S., Xie Q.,
RA   Liu N., Zhu H.;
RT   "ISG12a Restricts Hepatitis C Virus Infection through the Ubiquitination-
RT   Dependent Degradation Pathway.";
RL   J. Virol. 90:6832-6845(2016).
RN   [94]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 5A), AND INTERACTION WITH HOST TRIM14
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=27578425; DOI=10.1038/srep32336;
RA   Wang S., Chen Y., Li C., Wu Y., Guo L., Peng C., Huang Y., Cheng G.,
RA   Qin F.X.;
RT   "TRIM14 inhibits hepatitis C virus infection by SPRY domain-dependent
RT   targeted degradation of the viral NS5A protein.";
RL   Sci. Rep. 6:32336-32336(2016).
RN   [95]
RP   FUNCTION (VIROPORIN P7), AND SUBCELLULAR LOCATION (VIROPORIN P7).
RX   PubMed=29039530; DOI=10.3892/mmr.2017.7809;
RA   You D.G., Lee H.R., Kim W.K., Kim H.J., Lee G.Y., Yoo Y.D.;
RT   "Hepatitis C virus p7 induces mitochondrial depolarization of isolated
RT   liver mitochondria.";
RL   Mol. Med. Report. 16:9533-9538(2017).
RN   [96]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=28404852; DOI=10.1128/jvi.00280-17;
RA   Fan H., Qiao L., Kang K.D., Fan J., Wei W., Luo G.;
RT   "Attachment and Postattachment Receptors Important for Hepatitis C Virus
RT   Infection and Cell-to-Cell Transmission.";
RL   J. Virol. 91:0-0(2017).
RN   [97]
RP   INTERACTION WITH HOST TNFRSF21 (NON-STRUCTURAL PROTEIN 5A), AND FUNCTION
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=28743875; DOI=10.1038/s41598-017-06740-9;
RA   Luong T.T.D., Tran G.V.Q., Shin D.J., Lim Y.S., Hwang S.B.;
RT   "Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to
RT   Facilitate Viral Propagation.";
RL   Sci. Rep. 7:6445-6445(2017).
RN   [98]
RP   INTERACTION WITH HOST APOE (ENVELOPE GLYCOPROTEIN E2), FUNCTION (ENVELOPE
RP   GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=29695434; DOI=10.1128/jvi.00211-18;
RA   Kim J.Y., Ou J.J.;
RT   "Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced
RT   Autophagy.";
RL   J. Virol. 92:e00211-e00218(2018).
RN   [99]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4B).
RX   PubMed=29782532; DOI=10.1371/journal.ppat.1007075;
RA   Liang Y., Cao X., Ding Q., Zhao Y., He Z., Zhong J.;
RT   "Hepatitis C virus NS4B induces the degradation of TRIF to inhibit TLR3-
RT   mediated interferon signaling pathway.";
RL   PLoS Pathog. 14:E1007075-E1007075(2018).
RN   [100]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), AND FUNCTION (ENVELOPE GLYCOPROTEIN
RP   E1).
RX   PubMed=29505618; DOI=10.1371/journal.ppat.1006908;
RA   Douam F., Fusil F., Enguehard M., Dib L., Nadalin F., Schwaller L.,
RA   Hrebikova G., Mancip J., Mailly L., Montserret R., Ding Q., Maisse C.,
RA   Carlot E., Xu K., Verhoeyen E., Baumert T.F., Ploss A., Carbone A.,
RA   Cosset F.L., Lavillette D.;
RT   "A protein coevolution method uncovers critical features of the Hepatitis C
RT   Virus fusion mechanism.";
RL   PLoS Pathog. 14:e1006908-e1006908(2018).
RN   [101]
RP   INTERACTION WITH HOST NEURL3 (ENVELOPE GLYCOPROTEIN E1).
RX   PubMed=30111563; DOI=10.1128/jvi.01123-18;
RA   Zhao Y., Cao X., Guo M., Wang X., Yu T., Ye L., Han L., Hei L., Tao W.,
RA   Tong Y., Xu Y., Zhong J.;
RT   "Neuralized E3 Ubiquitin Protein Ligase 3 Is an Inducible Antiviral
RT   Effector That Inhibits Hepatitis C Virus Assembly by Targeting Viral E1
RT   Glycoprotein.";
RL   J. Virol. 92:0-0(2018).
RN   [102]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN E2), FUNCTION (SERINE PROTEASE/HELICASE
RP   NS3), FUNCTION (NON-STRUCTURAL PROTEIN 4A), SUBUNIT, AND INTERACTION WITH
RP   HOST SLC3A2 (ENVELOPE GLYCOPROTEIN E2).
RX   PubMed=30341327; DOI=10.1038/s41598-018-33861-6;
RA   Nguyen N.N.T., Lim Y.S., Nguyen L.P., Tran S.C., Luong T.T.D.,
RA   Nguyen T.T.T., Pham H.T., Mai H.N., Choi J.W., Han S.S., Hwang S.B.;
RT   "Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral
RT   Propagation.";
RL   Sci. Rep. 8:15486-15486(2018).
RN   [103]
RP   INTERACTION WITH HOST SPSB2 (ENVELOPE GLYCOPROTEIN E1), AND INTERACTION
RP   WITH HOST SPSB2 (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=31344133; DOI=10.1371/journal.pone.0219989;
RA   Wang M., Wang Y., Liu Y., Wang H., Xin X., Li J., Hao Y., Han L., Yu F.,
RA   Zheng C., Shen C.;
RT   "SPSB2 inhibits hepatitis C virus replication by targeting NS5A for
RT   ubiquitination and degradation.";
RL   PLoS ONE 14:e0219989-e0219989(2019).
RN   [104]
RP   PALMITOYLATION AT CYS-922 (PROTEASE NS2), SUBCELLULAR LOCATION (PROTEASE
RP   NS2), AND MUTAGENESIS OF CYS-922.
RX   PubMed=31597774; DOI=10.1128/jvi.00906-19;
RA   Wu M.J., Shanmugam S., Welsch C., Yi M.;
RT   "Palmitoylation of Hepatitis C Virus NS2 Regulates Its Subcellular
RT   Localization and NS2-NS3 Autocleavage.";
RL   J. Virol. 94:0-0(2019).
RN   [105]
RP   INTERACTION WITH HOST PACSIN2 (NON-STRUCTURAL PROTEIN 5A), AND FUNCTION
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=31801866; DOI=10.1128/jvi.01531-19;
RA   Nguyen L.P., Tran S.C., Suetsugu S., Lim Y.S., Hwang S.B.;
RT   "PACSIN2 Interacts with Nonstructural Protein 5A and Regulates Hepatitis C
RT   Virus Assembly.";
RL   J. Virol. 94:0-0(2020).
RN   [106]
RP   FUNCTION (VIROPORIN P7).
RX   PubMed=32156572; DOI=10.1016/j.biocel.2020.105738;
RA   Farag N.S., Breitinger U., Breitinger H.G., El Azizi M.A.;
RT   "Viroporins and inflammasomes: A key to understand virus-induced
RT   inflammation.";
RL   Int. J. Biochem. Cell Biol. 122:105738-105738(2020).
RN   [107]
RP   FUNCTION (RNA-DIRECTED RNA POLYMERASE).
RX   PubMed=37407817; DOI=10.1038/s41586-023-06301-3;
RA   Sherwood A.V., Rivera-Rangel L.R., Ryberg L.A., Larsen H.S., Anker K.M.,
RA   Costa R., Vaagboe C.B., Jakljevic E., Pham L.V., Fernandez-Antunez C.,
RA   Indrisiunaite G., Podolska-Charlery A., Grothen J.E.R., Langvad N.W.,
RA   Fossat N., Offersgaard A., Al-Chaer A., Nielsen L., Kusnierczyk A.,
RA   Soelund C., Weis N., Gottwein J.M., Holmbeck K., Bottaro S., Ramirez S.,
RA   Bukh J., Scheel T.K.H., Vinther J.;
RT   "Hepatitis C virus RNA is 5'-capped with flavin adenine dinucleotide.";
RL   Nature 619:811-818(2023).
RN   [108] {ECO:0007744|PDB:1HEI}
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1206-1656 IN COMPLEX WITH
RP   CALCIUM.
RX   PubMed=9187654; DOI=10.1038/nsb0697-463;
RA   Yao N., Hesson T., Cable M.B., Hong Z., Kwong A.D., Le H.V., Weber P.C.;
RT   "Structure of the hepatitis C virus RNA helicase domain.";
RL   Nat. Struct. Biol. 4:463-467(1997).
RN   [109] {ECO:0007744|PDB:1A1R}
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1019-1206 IN COMPLEX WITH
RP   NON-STRUCTURAL PROTEIN 4A, INTERACTION WITH NON-STRUCTURAL PROTEIN 4A
RP   (SERINE PROTEASE/HELICASE NS3), INTERACTION WITH SERINE PROTEASE/HELICASE
RP   NS3 (NON-STRUCTURAL PROTEIN 4A), AND ACTIVE SITE (SERINE PROTEASE/HELICASE
RP   NS3).
RX   PubMed=8861917; DOI=10.1016/s0092-8674(00)81351-3;
RA   Kim J.L., Morgenstern K.A., Lin C., Fox T., Dwyer M.D., Landro J.A.,
RA   Chambers S.P., Markland W., Lepre C.A., O'Malley E.T., Harbeson S.L.,
RA   Rice C.M., Murcko M.A., Caron P.R., Thomson J.A.;
RT   "Crystal structure of the hepatitis C virus NS3 protease domain complexed
RT   with a synthetic NS4A cofactor peptide.";
RL   Cell 87:343-355(1996).
RN   [110]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1193-1659.
RX   PubMed=9493270; DOI=10.1016/s0969-2126(98)00010-0;
RA   Kim J.L., Morgenstern K.A., Griffith J.P., Dwyer M.D., Thomson J.A.,
RA   Murcko M.A., Lin C., Caron P.R.;
RT   "Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide:
RT   the crystal structure provides insights into the mode of unwinding.";
RL   Structure 6:89-100(1998).
RN   [111]
RP   STRUCTURE BY NMR OF 1353-1507.
RX   PubMed=11846566; DOI=10.1006/jmbi.2001.5146;
RA   Liu D., Wang Y.-S., Gesell J.J., Wyss D.F.;
RT   "Solution structure and backbone dynamics of an engineered arginine-rich
RT   subdomain 2 of the hepatitis C virus NS3 RNA helicase.";
RL   J. Mol. Biol. 314:543-561(2001).
RN   [112]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1027-1207.
RX   PubMed=12465917; DOI=10.1021/ol027014p;
RA   Andrews D.M., Chaignot H., Coomber B.A., Good A.C., Hind S.L.,
RA   Johnson M.R., Jones P.S., Mills G., Robinson J.E., Skarzynski T.,
RA   Slater M.J., Somers D.O.;
RT   "Pyrrolidine-5,5-trans-lactams. 2. The use of X-ray crystal structure data
RT   in the optimization of P3 and P4 substituents.";
RL   Org. Lett. 4:4479-4482(2002).
RN   [113] {ECO:0007744|PDB:1R7C, ECO:0007744|PDB:1R7D, ECO:0007744|PDB:1R7E, ECO:0007744|PDB:1R7F, ECO:0007744|PDB:1R7G}
RP   STRUCTURE BY NMR OF 1973-2003, TOPOLOGY (NON-STRUCTURAL PROTEIN 5A),
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 5A), AND DOMAIN
RP   (NON-STRUCTURAL PROTEIN 5A).
RX   PubMed=15247283; DOI=10.1074/jbc.m404761200;
RA   Penin F., Brass V., Appel N., Ramboarina S., Montserret R., Ficheux D.,
RA   Blum H.E., Bartenschlager R., Moradpour D.;
RT   "Structure and function of the membrane anchor domain of hepatitis C virus
RT   nonstructural protein 5A.";
RL   J. Biol. Chem. 279:40835-40843(2004).
RN   [114]
RP   X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 903-1026, MUTAGENESIS OF HIS-952
RP   AND CYS-993, ACTIVE SITE (PROTEASE NS2), AND SUBUNIT (PROTEASE NS2).
RX   PubMed=16862121; DOI=10.1038/nature04975;
RA   Lorenz I.C., Marcotrigiano J., Dentzer T.G., Rice C.M.;
RT   "Structure of the catalytic domain of the hepatitis C virus NS2-3
RT   protease.";
RL   Nature 442:831-835(2006).
RN   [115] {ECO:0007744|PDB:2KDR}
RP   STRUCTURE BY NMR OF 1938-1965.
RX   PubMed=19692468; DOI=10.1128/jvi.01122-09;
RA   Gouttenoire J., Montserret R., Kennel A., Penin F., Moradpour D.;
RT   "An amphipathic alpha-helix at the C terminus of hepatitis C virus
RT   nonstructural protein 4B mediates membrane association.";
RL   J. Virol. 83:11378-11384(2009).
RN   [116] {ECO:0007744|PDB:2JXF}
RP   STRUCTURE BY NMR OF 1751-1780.
RX   PubMed=19357161; DOI=10.1128/jvi.02663-08;
RA   Gouttenoire J., Castet V., Montserret R., Arora N., Raussens V.,
RA   Ruysschaert J.M., Diesis E., Blum H.E., Penin F., Moradpour D.;
RT   "Identification of a novel determinant for membrane association in
RT   hepatitis C virus nonstructural protein 4B.";
RL   J. Virol. 83:6257-6268(2009).
RN   [117] {ECO:0007744|PDB:2XI2, ECO:0007744|PDB:2XI3}
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2421-2990 IN COMPLEX WITH GTP,
RP   FUNCTION (RNA-DIRECTED RNA POLYMERASE), AND CATALYTIC ACTIVITY
RP   (RNA-DIRECTED RNA POLYMERASE).
RX   PubMed=20729191; DOI=10.1074/jbc.m110.151316;
RA   Harrus D., Ahmed-El-Sayed N., Simister P.C., Miller S., Triconnet M.,
RA   Hagedorn C.H., Mahias K., Rey F.A., Astier-Gin T., Bressanelli S.;
RT   "Further insights into the roles of GTP and the C terminus of the hepatitis
RT   C virus polymerase in the initiation of RNA synthesis.";
RL   J. Biol. Chem. 285:32906-32918(2010).
RN   [118] {ECO:0007744|PDB:3RC4, ECO:0007744|PDB:3RC5}
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1026-1208 IN COMPLEX WITH ZINC,
RP   AND FUNCTION (NON-STRUCTURAL PROTEIN 4A).
RX   PubMed=21507982; DOI=10.1128/jvi.00377-11;
RA   Romano K.P., Laine J.M., Deveau L.M., Cao H., Massi F., Schiffer C.A.;
RT   "Molecular mechanisms of viral and host cell substrate recognition by
RT   hepatitis C virus NS3/4A protease.";
RL   J. Virol. 85:6106-6116(2011).
RN   [119] {ECO:0007744|PDB:4MWF}
RP   X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 412-459 AND 486-645, AND
RP   GLYCOSYLATION AT ASN-430; ASN-532; ASN-540; ASN-556 AND ASN-623.
RX   PubMed=24288331; DOI=10.1126/science.1243876;
RA   Kong L., Giang E., Nieusma T., Kadam R.U., Cogburn K.E., Hua Y., Dai X.,
RA   Stanfield R.L., Burton D.R., Ward A.B., Wilson I.A., Law M.;
RT   "Hepatitis C virus E2 envelope glycoprotein core structure.";
RL   Science 342:1090-1094(2013).
CC   -!- FUNCTION: [Mature core protein]: Packages viral RNA to form a viral
CC       nucleocapsid, and promotes virion budding (Probable). Participates in
CC       the viral particle production as a result of its interaction with the
CC       non-structural protein 5A (By similarity). Binds RNA and may function
CC       as a RNA chaperone to induce the RNA structural rearrangements taking
CC       place during virus replication (PubMed:18033802). Modulates viral
CC       translation initiation by interacting with viral IRES and 40S ribosomal
CC       subunit (By similarity). Affects various cell signaling pathways, host
CC       immunity and lipid metabolism (Probable). Prevents the establishment of
CC       cellular antiviral state by blocking the interferon-alpha/beta (IFN-
CC       alpha/beta) and IFN-gamma signaling pathways and by blocking the
CC       formation of phosphorylated STAT1 and promoting ubiquitin-mediated
CC       proteasome-dependent degradation of STAT1 (PubMed:23799612) (By
CC       similarity). Activates STAT3 leading to cellular transformation (By
CC       similarity). Regulates the activity of cellular genes, including c-myc
CC       and c-fos (By similarity). May repress the promoter of p53, and
CC       sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By
CC       similarity). Represses cell cycle negative regulating factor CDKN1A,
CC       thereby interrupting an important check point of normal cell cycle
CC       regulation (By similarity). Targets transcription factors involved in
CC       the regulation of inflammatory responses and in the immune response:
CC       suppresses NF-kappa-B activation, and activates AP-1 (By similarity).
CC       Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation
CC       of T-lymphocytes proliferation (PubMed:11086025, PubMed:17881511).
CC       Alters lipid metabolism by interacting with hepatocellular proteins
CC       involved in lipid accumulation and storage (PubMed:14602201). Induces
CC       up-regulation of FAS promoter activity, and thereby contributes to the
CC       increased triglyceride accumulation in hepatocytes (steatosis)
CC       (PubMed:14602201). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P29846,
CC       ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:11086025,
CC       ECO:0000269|PubMed:14602201, ECO:0000269|PubMed:17881511,
CC       ECO:0000269|PubMed:18033802, ECO:0000269|PubMed:23799612, ECO:0000305}.
CC   -!- FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope
CC       glycoprotein E2, which mediates virus attachment to the host cell,
CC       virion internalization through clathrin-dependent endocytosis and
CC       fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion
CC       with the host cell is most likely mediated by both E1 and E2, through
CC       conformational rearrangements of the heterodimer required for fusion
CC       rather than a classical class II fusion mechanism (PubMed:16533059,
CC       PubMed:29505618, PubMed:24698129). E1/E2 heterodimer binds host
CC       apolipoproteins such as APOB and APOE thereby forming a lipo-viro-
CC       particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241).
CC       APOE associated to the LVP allows the initial virus attachment to cell
CC       surface receptors such as the heparan sulfate proteoglycans (HSPGs),
CC       syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein
CC       receptor (LDLR) and scavenger receptor class B type I (SCARB1)
CC       (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852,
CC       PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2
CC       exposure and binding of E2 to SCARB1 and the tetraspanin CD81
CC       (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81
CC       activates the epithelial growth factor receptor (EGFR) signaling
CC       pathway (PubMed:22855500). Diffusion of the complex E1/E2-EGFR-SCARB1-
CC       CD81 to the cell lateral membrane allows further interaction with
CC       Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry
CC       (PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:20375010,
CC       PubMed:19182773) (By similarity). {ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:12356718, ECO:0000269|PubMed:12913001,
CC       ECO:0000269|PubMed:12970454, ECO:0000269|PubMed:14990718,
CC       ECO:0000269|PubMed:16533059, ECO:0000269|PubMed:16894197,
CC       ECO:0000269|PubMed:19182773, ECO:0000269|PubMed:20375010,
CC       ECO:0000269|PubMed:22767607, ECO:0000269|PubMed:22855500,
CC       ECO:0000269|PubMed:24038151, ECO:0000269|PubMed:24698129,
CC       ECO:0000269|PubMed:24838241, ECO:0000269|PubMed:25122793,
CC       ECO:0000269|PubMed:28404852, ECO:0000269|PubMed:29505618,
CC       ECO:0000269|PubMed:29695434}.
CC   -!- FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope
CC       glycoprotein E1, which mediates virus attachment to the host cell,
CC       virion internalization through clathrin-dependent endocytosis and
CC       fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion
CC       with the host cell is most likely mediated by both E1 and E2, through
CC       conformational rearrangements of the heterodimer required for fusion
CC       rather than a classical class II fusion mechanism (PubMed:16533059,
CC       PubMed:29505618, PubMed:24698129). The interaction between E2 and host
CC       apolipoprotein E/APOE allows the proper assembly, maturation and
CC       infectivity of the viral particles (PubMed:25122793, PubMed:29695434).
CC       This interaction is probably promoted via the up-regulation of cellular
CC       autophagy by the virus (PubMed:29695434). E1/E2 heterodimer binds host
CC       apolipoproteins such as APOB and APOE thereby forming a lipo-viro-
CC       particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241).
CC       APOE associated to the LVP allows the initial virus attachment to cell
CC       surface receptors such as the heparan sulfate proteoglycans (HSPGs),
CC       syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein
CC       receptor (LDLR) and scavenger receptor class B type I (SCARB1)
CC       (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852,
CC       PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2
CC       exposure and binding of E2 to SCARB1 and the tetraspanin CD81
CC       (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81
CC       activates the epithelial growth factor receptor (EGFR) signaling
CC       pathway (PubMed:20375010, PubMed:12970454, PubMed:24038151,
CC       PubMed:12913001, PubMed:19182773, PubMed:22855500) (By similarity).
CC       Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral
CC       membrane allows further interaction with Claudin 1 (CLDN1) and occludin
CC       (OCLN) to finally trigger HCV entry (PubMed:20375010, PubMed:12970454,
CC       PubMed:24038151, PubMed:12913001, PubMed:19182773) (By similarity).
CC       Inhibits host EIF2AK2/PKR activation, preventing the establishment of
CC       an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and
CC       CLEC4M/DC-SIGNR, which are respectively found on DCs, and on liver
CC       sinusoidal endothelial cells and macrophage-like cells of lymph node
CC       sinuses (PubMed:15371595). These interactions allow the capture of
CC       circulating HCV particles by these cells and subsequent facilitated
CC       transmission to permissive cells such as hepatocytes and lymphocyte
CC       subpopulations (PubMed:15371595). The interaction between E2 and host
CC       amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may
CC       facilitate viral entry into host cell (PubMed:30341327).
CC       {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:12356718, ECO:0000269|PubMed:12913001,
CC       ECO:0000269|PubMed:12970454, ECO:0000269|PubMed:14990718,
CC       ECO:0000269|PubMed:15371595, ECO:0000269|PubMed:16533059,
CC       ECO:0000269|PubMed:16894197, ECO:0000269|PubMed:19182773,
CC       ECO:0000269|PubMed:20375010, ECO:0000269|PubMed:22767607,
CC       ECO:0000269|PubMed:22855500, ECO:0000269|PubMed:24038151,
CC       ECO:0000269|PubMed:24698129, ECO:0000269|PubMed:24838241,
CC       ECO:0000269|PubMed:25122793, ECO:0000269|PubMed:28404852,
CC       ECO:0000269|PubMed:29505618, ECO:0000269|PubMed:29695434,
CC       ECO:0000269|PubMed:30341327}.
CC   -!- FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin
CC       and plays an essential role in the assembly, envelopment and secretion
CC       of viral particles (PubMed:12719519, PubMed:20824094, PubMed:27320856).
CC       Participates in virus envelopment by coordinating the encounter between
CC       NS5A and NS2-based assembly sites loaded with E1/E2 heterodimer, which
CC       subsequently leads to nucleocapsid envelopment (By similarity). Creates
CC       a pore in acidic organelles and releases Ca(2+) and H(+) in the
CC       cytoplasm of infected cells, leading to a productive viral infection
CC       (Probable) (PubMed:20824094). High levels of cytoplasmic Ca(2+) may
CC       trigger membrane trafficking and transport of viral ER-associated
CC       proteins to viroplasms, sites of viral genome replication (Probable).
CC       The release of Ca(2+) may also activate the inflamasome leading to
CC       chronic inflammation (Probable) (PubMed:31801866). Targets also host
CC       mitochondria and induces mitochondrial depolarization
CC       (PubMed:29039530). In addition of its role as a viroporin, acts as a
CC       lipid raft adhesion factor (PubMed:27320856).
CC       {ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:12719519,
CC       ECO:0000269|PubMed:20824094, ECO:0000269|PubMed:27320856,
CC       ECO:0000269|PubMed:29039530, ECO:0000303|PubMed:31801866, ECO:0000305,
CC       ECO:0000305|PubMed:14741348, ECO:0000305|PubMed:24006444}.
CC   -!- FUNCTION: [Protease NS2]: Cysteine protease required for the
CC       proteolytic auto-cleavage between the non-structural proteins NS2 and
CC       NS3 (PubMed:8248148). The N-terminus of NS3 is required for the
CC       function of NS2 protease (active region NS2-3) (By similarity).
CC       Promotes the initiation of viral particle assembly by mediating the
CC       interaction between structural and non-structural proteins
CC       (PubMed:21147927). {ECO:0000250|UniProtKB:P26663,
CC       ECO:0000269|PubMed:21147927, ECO:0000269|PubMed:8248148}.
CC   -!- FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic
CC       activities: serine protease with a chymotrypsin-like fold, NTPase and
CC       RNA helicase (PubMed:25551442). NS3 serine protease, in association
CC       with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B,
CC       NS4B-NS5A and NS5A-NS5B (PubMed:8189513, PubMed:8035505,
CC       PubMed:8386278). The NS3/NS4A complex prevents phosphorylation of host
CC       IRF3, thus preventing the establishment of dsRNA induced antiviral
CC       state (By similarity). The NS3/NS4A complex induces host amino acid
CC       transporter component SLC3A2, thus contributing to HCV propagation
CC       (PubMed:30341327). NS3 RNA helicase binds to RNA and unwinds both dsDNA
CC       and dsRNA in the 3' to 5' direction, and likely resolves RNA
CC       complicated stable secondary structures in the template strand
CC       (Probable). Binds a single ATP and catalyzes the unzipping of a single
CC       base pair of dsRNA (PubMed:21940894). Inhibits host antiviral proteins
CC       TBK1 and IRF3 thereby preventing the establishment of an antiviral
CC       state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the
CC       establishment of an antiviral state (PubMed:16301520, PubMed:16177806).
CC       Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and
CC       preventing the establishment of an antiviral state (PubMed:15710891).
CC       {ECO:0000250|UniProtKB:Q9WMX2, ECO:0000269|PubMed:15710891,
CC       ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:16301520,
CC       ECO:0000269|PubMed:21940894, ECO:0000269|PubMed:25551442,
CC       ECO:0000269|PubMed:30341327, ECO:0000269|PubMed:8035505,
CC       ECO:0000269|PubMed:8189513, ECO:0000269|PubMed:8386278,
CC       ECO:0000305|PubMed:15269774}.
CC   -!- FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a
CC       non-covalent complex with the N-terminal of NS3 serine protease
CC       (PubMed:8189513, PubMed:21507982). The NS3/NS4A complex prevents
CC       phosphorylation of host IRF3, thus preventing the establishment of
CC       dsRNA induced antiviral state (By similarity). The NS3/NS4A complex
CC       induces host amino acid transporter component SLC3A2, thus contributing
CC       to HCV propagation (PubMed:30341327). {ECO:0000250|UniProtKB:Q9WMX2,
CC       ECO:0000269|PubMed:21507982, ECO:0000269|PubMed:30341327,
CC       ECO:0000269|PubMed:8189513}.
CC   -!- FUNCTION: [Non-structural protein 4B]: Induces a specific membrane
CC       alteration that serves as a scaffold for the virus replication complex
CC       (PubMed:12021330). This membrane alteration gives rise to the so-called
CC       ER-derived membranous web that contains the replication complex
CC       (PubMed:12021330). NS4B self-interaction contributes to its function in
CC       membranous web formation (PubMed:16731940). Promotes host TRIF protein
CC       degradation in a CASP8-dependent manner thereby inhibiting host TLR3-
CC       mediated interferon signaling (PubMed:29782532). Disrupts the
CC       interaction between STING and TBK1 contributing to the inhibition of
CC       interferon signaling (PubMed:23542348). {ECO:0000269|PubMed:12021330,
CC       ECO:0000269|PubMed:16731940, ECO:0000269|PubMed:23542348,
CC       ECO:0000269|PubMed:29782532}.
CC   -!- FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is
CC       indispensable for viral replication and assembly (PubMed:27578425).
CC       Both hypo- and hyperphosphorylated states are required for the viral
CC       life cycle (By similarity). The hyperphosphorylated form of NS5A is an
CC       inhibitor of viral replication (By similarity). Involved in RNA-binding
CC       and especially in binding to the viral genome (Probable). Zinc is
CC       essential for RNA-binding (PubMed:20926572). Participates in the viral
CC       particle production as a result of its interaction with the viral
CC       mature core protein (By similarity). Its interaction with host VAPB may
CC       target the viral replication complex to vesicles (By similarity). Down-
CC       regulates viral IRES translation initiation (By similarity). Mediates
CC       interferon resistance, presumably by interacting with and inhibiting
CC       host EIF2AK2/PKR (PubMed:16951545). Prevents BIN1-induced apoptosis
CC       (PubMed:16530520). Acts as a transcriptional activator of some host
CC       genes important for viral replication when localized in the nucleus (By
CC       similarity). Via the interaction with host PACSIN2, modulates lipid
CC       droplet formation in order to promote virion assembly
CC       (PubMed:31801866). Modulates TNFRSF21/DR6 signaling pathway for viral
CC       propagation (PubMed:28743875). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000250|UniProtKB:Q9WMX2, ECO:0000269|PubMed:16530520,
CC       ECO:0000269|PubMed:16951545, ECO:0000269|PubMed:20926572,
CC       ECO:0000269|PubMed:25683609, ECO:0000269|PubMed:27578425,
CC       ECO:0000269|PubMed:28743875, ECO:0000269|PubMed:31801866,
CC       ECO:0000305|PubMed:20926572}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase
CC       that performs primer-template recognition and RNA synthesis during
CC       viral replication (PubMed:20729191). Initiates RNA
CC       transcription/replication at a flavin adenine dinucleotide (FAD),
CC       resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of
CC       viral 5' RNA by host pattern recognition receptors can be bypassed
CC       (PubMed:37407817), thereby evading activation of antiviral pathways.
CC       {ECO:0000269|PubMed:20729191, ECO:0000269|PubMed:37407817}.
CC   -!- CATALYTIC ACTIVITY: [Serine protease/helicase NS3]:
CC       Reaction=Hydrolysis of four peptide bonds in the viral precursor
CC         polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr
CC         in P1 and Ser or Ala in P1'.; EC=3.4.21.98;
CC         Evidence={ECO:0000269|PubMed:8035505, ECO:0000269|PubMed:8386278};
CC   -!- CATALYTIC ACTIVITY: [Serine protease/helicase NS3]:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC         Evidence={ECO:0000269|PubMed:15269774, ECO:0000269|PubMed:16397502,
CC         ECO:0000269|PubMed:25551442};
CC   -!- CATALYTIC ACTIVITY: [Serine protease/helicase NS3]:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000269|PubMed:15269774, ECO:0000269|PubMed:16397502,
CC         ECO:0000269|PubMed:25551442};
CC   -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC         COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC         EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539,
CC         ECO:0000269|PubMed:20729191};
CC   -!- COFACTOR: [Protease NS2]:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P26663};
CC       Note=Activity of protease NS2 is dependent on zinc ions and completely
CC       inhibited by EDTA. This is probably due to the fact that NS2 protease
CC       activity needs NS3 N-terminus that binds a zinc atom (active region
CC       NS2-3). {ECO:0000250|UniProtKB:P26663};
CC   -!- COFACTOR: [Serine protease/helicase NS3]:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P26663};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q9WMX2};
CC       Note=Binds 1 zinc ion, which has a structural role (By similarity). The
CC       magnesium ion is essential for the helicase activity (By similarity).
CC       {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2};
CC   -!- COFACTOR: [RNA-directed RNA polymerase]:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P26663};
CC       Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal
CC       center. {ECO:0000250|UniProtKB:P26663};
CC   -!- ACTIVITY REGULATION: [Viroporin p7]: Inhibited by the antiviral drug
CC       hexamethylene amiloride (By similarity). Inhibited by amantadine
CC       (PubMed:12560074). Inhibition by amantadine appears to be genotype-
CC       dependent (By similarity). Also inhibited by long-alkyl-chain
CC       iminosugar derivatives (PubMed:12719519).
CC       {ECO:0000250|UniProtKB:P26662, ECO:0000269|PubMed:12560074,
CC       ECO:0000269|PubMed:12719519}.
CC   -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Activity is up-
CC       regulated by PRK2/PKN2-mediated phosphorylation.
CC       {ECO:0000269|PubMed:15364941}.
CC   -!- SUBUNIT: [Mature core protein]: Homooligomer (PubMed:25351725).
CC       Interacts with E1 (via C-terminus) (PubMed:8764026). Interacts with the
CC       non-structural protein 5A (By similarity). Interacts (via N-terminus)
CC       with host STAT1 (via SH2 domain); this interaction results in decreased
CC       STAT1 phosphorylation and ubiquitin-mediated proteasome-dependent STAT1
CC       degradation, leading to decreased IFN-stimulated gene transcription
CC       (PubMed:23799612). Interacts with host STAT3; this interaction
CC       constitutively activates STAT3 (By similarity). Associates with host
CC       LTBR receptor (By similarity). Interacts with host TNFRSF1A receptor
CC       and possibly induces apoptosis (By similarity). Interacts with host
CC       HNRPK (By similarity). Interacts with host YWHAE (By similarity).
CC       Interacts with host UBE3A/E6AP (By similarity). Interacts with host
CC       DDX3X (By similarity). Interacts with host APOA2 (By similarity).
CC       Interacts with host RXRA protein (By similarity). Interacts with host
CC       SP110 isoform 3/Sp110b; this interaction sequesters the transcriptional
CC       corepressor SP110 away from the nucleus (By similarity). Interacts with
CC       host CREB3 nuclear transcription protein; this interaction triggers
CC       cell transformation (By similarity). Interacts with host ACY3
CC       (PubMed:19486448). Interacts with host C1QR1 (PubMed:11086025).
CC       Interacts with host RBM24; this interaction, which enhances the
CC       interaction of the mature core protein with 5'-UTR, may inhibit viral
CC       translation and favor replication (By similarity). Interacts (via N-
CC       terminus) with host EIF2AK2/PKR (via N-terminus); this interaction
CC       induces the autophosphorylation of EIF2AK2 (By similarity). Part of the
CC       viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A,
CC       NS5A and the mature core protein (By similarity).
CC       {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P29846,
CC       ECO:0000250|UniProtKB:Q03463, ECO:0000250|UniProtKB:Q5EG65,
CC       ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:11086025,
CC       ECO:0000269|PubMed:19486448, ECO:0000269|PubMed:23799612,
CC       ECO:0000269|PubMed:25351725, ECO:0000269|PubMed:8764026}.
CC   -!- SUBUNIT: [Envelope glycoprotein E1]: Forms a heterodimer with envelope
CC       glycoprotein E2 (PubMed:11145889, PubMed:14990718, PubMed:24038151).
CC       Interacts with mature core protein (PubMed:8764026). Interacts with
CC       protease NS2 (PubMed:21147927). The heterodimer E1/E2 interacts with
CC       host CLDN1; this interaction plays a role in viral entry into host cell
CC       (PubMed:24038151). Interacts with host SPSB2 (via C-terminus)
CC       (PubMed:31344133). Part of the viral assembly initiation complex
CC       composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein
CC       (By similarity). Interacts with host NEURL3; this interaction prevents
CC       E1 binding to glycoprotein E2 (PubMed:30111563).
CC       {ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:11145889,
CC       ECO:0000269|PubMed:14990718, ECO:0000269|PubMed:21147927,
CC       ECO:0000269|PubMed:24038151, ECO:0000269|PubMed:30111563,
CC       ECO:0000269|PubMed:31344133, ECO:0000269|PubMed:8764026}.
CC   -!- SUBUNIT: [Envelope glycoprotein E2]: Forms a heterodimer with envelope
CC       glycoprotein E1 (PubMed:11145889, PubMed:14990718, PubMed:24038151).
CC       Interacts with host CD81 and SCARB1 receptors; these interactions play
CC       a role in viral entry into host cell (PubMed:12970454, PubMed:12356718,
CC       PubMed:12913001). Interacts with host EIF2AK2/PKR; this interaction
CC       inhibits EIF2AK2 and probably allows the virus to evade the innate
CC       immune response (PubMed:10390359). Interacts with host CD209/DC-SIGN
CC       and CLEC4M/DC-SIGNR (PubMed:15371595). Interact with host SPCS1; this
CC       interaction is essential for viral particle assembly (By similarity).
CC       Interacts with protease NS2 (PubMed:21147927). The heterodimer E1/E2
CC       interacts with host CLDN1; this interaction plays a role in viral entry
CC       into host cell (PubMed:24038151). Part of the viral assembly initiation
CC       complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core
CC       protein (By similarity). Interacts with host SLC3A2/4F2hc; the
CC       interaction may facilitate viral entry into host cell
CC       (PubMed:30341327). Interacts with human PLSCR1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2,
CC       ECO:0000269|PubMed:10390359, ECO:0000269|PubMed:11145889,
CC       ECO:0000269|PubMed:12356718, ECO:0000269|PubMed:12913001,
CC       ECO:0000269|PubMed:12970454, ECO:0000269|PubMed:14990718,
CC       ECO:0000269|PubMed:15371595, ECO:0000269|PubMed:21147927,
CC       ECO:0000269|PubMed:24038151, ECO:0000269|PubMed:30341327}.
CC   -!- SUBUNIT: [Viroporin p7]: Homohexamer (PubMed:12560074). Homoheptamer
CC       (By similarity). Interacts with protease NS2 (By similarity).
CC       {ECO:0000250|UniProtKB:O92972, ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:12560074}.
CC   -!- SUBUNIT: [Protease NS2]: Homodimer (PubMed:16862121). Interacts with
CC       host SPCS1; this interaction is essential for viral particle assembly
CC       (By similarity). Interacts with envelope glycoprotein E1
CC       (PubMed:21147927). Interacts with envelope glycoprotein E2
CC       (PubMed:21147927). Interacts with viroporin p7 (By similarity).
CC       Interacts with serine protease/helicase NS3 (PubMed:21147927). Part of
CC       the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the
CC       RNA-directed RNA polymerase embedded in an ER-derived membranous web
CC       (PubMed:12692249, PubMed:12692242). Part of the viral assembly
CC       initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the
CC       mature core protein (By similarity). {ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:12692242, ECO:0000269|PubMed:12692249,
CC       ECO:0000269|PubMed:16862121, ECO:0000269|PubMed:21147927}.
CC   -!- SUBUNIT: [Serine protease/helicase NS3]: Interacts with protease NS2
CC       (PubMed:21147927). Interacts with non-structural protein 4A; this
CC       interaction stabilizes the folding of NS3 serine protease (By
CC       similarity). NS3-NS4A interaction is essential for NS3 activation and
CC       allows membrane anchorage of the latter (PubMed:7769699,
CC       PubMed:8861917). NS3/NS4A complex also prevents phosphorylation of host
CC       IRF3, thus preventing the establishment of dsRNA induced antiviral
CC       state (By similarity). Interacts with host MAVS; this interaction leads
CC       to the cleavage and inhibition of host MAVS (PubMed:16177806,
CC       PubMed:16301520). Interacts with host TICAM1; this interaction leads to
CC       the cleavage and inhibition of host TICAM1 (PubMed:16177806,
CC       PubMed:16301520). Interacts with host TANK-binding kinase/TBK1; this
CC       interaction results in the inhibition of the association between TBK1
CC       and IRF3, which leads to the inhibition of IRF3 activation (By
CC       similarity). Interacts with host RBM24 (By similarity). Part of the
CC       replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-
CC       directed RNA polymerase embedded in an ER-derived membranous web
CC       (PubMed:12021330, PubMed:12692249, PubMed:12692242). Part of the viral
CC       assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A
CC       and the mature core protein (By similarity).
CC       {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000250|UniProtKB:Q9WMX2, ECO:0000269|PubMed:12021330,
CC       ECO:0000269|PubMed:12692242, ECO:0000269|PubMed:12692249,
CC       ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:16301520,
CC       ECO:0000269|PubMed:21147927, ECO:0000269|PubMed:7769699,
CC       ECO:0000269|PubMed:8861917}.
CC   -!- SUBUNIT: [Non-structural protein 4A]: Interacts with NS3 serine
CC       protease; this interaction stabilizes the folding of NS3 serine
CC       protease (PubMed:8861917, PubMed:7769699). NS3-NS4A interaction is
CC       essential for NS3 activation and allows membrane anchorage of the
CC       latter (PubMed:8861917, PubMed:7769699). Interacts with non-structural
CC       protein 5A (via N-terminus) (By similarity). Part of the replication
CC       complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA
CC       polymerase embedded in an ER-derived membranous web (PubMed:12021330,
CC       PubMed:12692249, PubMed:12692242). Part of the viral assembly
CC       initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the
CC       mature core protein (By similarity). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:12021330,
CC       ECO:0000269|PubMed:12692242, ECO:0000269|PubMed:12692249,
CC       ECO:0000269|PubMed:7769699, ECO:0000269|PubMed:8861917}.
CC   -!- SUBUNIT: [Non-structural protein 4B]: Homomultimer (PubMed:23868571).
CC       Interacts with non-structural protein NS5A (PubMed:23868571). Interacts
CC       with host PLA2G4C; this interaction likely initiates the recruitment of
CC       replication complexes to lipid droplets (By similarity). Interacts with
CC       host STING; this interaction disrupts the interaction between STING and
CC       TBK1 thereby suppressing the interferon signaling (PubMed:23542348).
CC       Interacts with host METTL22; this interaction may promote the
CC       recruitment of NS4B in the proximity of lipid droplet
CC       (PubMed:26185986). Part of the replication complex composed of NS2,
CC       NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in
CC       an ER-derived membranous web (PubMed:12021330, PubMed:12692249,
CC       PubMed:12692242). {ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:12021330, ECO:0000269|PubMed:12692242,
CC       ECO:0000269|PubMed:12692249, ECO:0000269|PubMed:23542348,
CC       ECO:0000269|PubMed:23868571, ECO:0000269|PubMed:26185986}.
CC   -!- SUBUNIT: [Non-structural protein 5A]: Monomer (PubMed:20926572).
CC       Homodimer; dimerization is required for RNA-binding (PubMed:20926572).
CC       Interacts with the mature core protein (By similarity). Interacts (via
CC       N-terminus) with non-structural protein 4A (By similarity). Interacts
CC       with non-structural protein 4B (PubMed:23868571). Interacts (via region
CC       D2) with RNA-directed RNA polymerase (Probable). Part of the viral
CC       assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A
CC       and the mature core protein (By similarity). Part of the replication
CC       complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA
CC       polymerase embedded in an ER-derived membranous web (PubMed:12021330,
CC       PubMed:12692249, PubMed:12692242). Interacts with host GRB2 (By
CC       similarity). Interacts with host BIN1 (PubMed:16530520). Interacts with
CC       host PIK3R1 (By similarity). Interacts with host SRCAP
CC       (PubMed:10702287). Interacts with host FKBP8 (By similarity). Interacts
CC       (via C-terminus) with host VAPB (via MSP domain) (PubMed:22720086)
CC       (Probable). Interacts with host EIF2AK2/PKR; this interaction leads to
CC       disruption of EIF2AK2 dimerization by NS5A and probably allows the
CC       virus to evade the innate immune response (Probable). Interacts (via N-
CC       terminus) with host PACSIN2 (via N-terminus); this interaction
CC       attenuates protein kinase C alpha-mediated phosphorylation of PACSIN2
CC       by disrupting the interaction between PACSIN2 and PRKCA
CC       (PubMed:31801866). Interacts (via N-terminus) with host SRC kinase (via
CC       SH2 domain) (By similarity). Interacts with most Src-family kinases (By
CC       similarity). Interacts with host IFI27 and SKP2; promotes the
CC       ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766).
CC       Interacts with host GPS2 (By similarity). Interacts with host TNFRSF21;
CC       this interaction allows the modulation by the virus of JNK, p38 MAPK,
CC       STAT3, and Akt signaling pathways in a DR6-dependent manner
CC       (PubMed:28743875). Interacts (via N-terminus) with host CIDEB (via N-
CC       terminus); this interaction seems to regulate the association of HCV
CC       particles with APOE (PubMed:27282740). Interacts with host CHKA/Choline
CC       Kinase-alpha; CHKA bridges host PI4KA and NS5A and potentiates NS5A-
CC       stimulated PI4KA activity, which then facilitates the targeting of the
CC       ternary complex to the ER for viral replication (By similarity).
CC       Interacts with host SPSB2 (via C-terminus); this interaction targets
CC       NS5A for ubiquitination and degradation (PubMed:31344133). Interacts
CC       with host RAB18; this interaction may promote the association of NS5A
CC       and other replicase components with lipid droplets (By similarity).
CC       Interacts (via region D2) with host PPIA/CYPA; the interaction
CC       stimulates RNA-binding ability of NS5A and is dependent on the
CC       peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA (Probable).
CC       Interacts with host TRIM14; this interaction induces the degradation of
CC       NS5A (PubMed:27578425). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P26664,
CC       ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:10702287,
CC       ECO:0000269|PubMed:11801599, ECO:0000269|PubMed:12021330,
CC       ECO:0000269|PubMed:12692242, ECO:0000269|PubMed:12692249,
CC       ECO:0000269|PubMed:16530520, ECO:0000269|PubMed:20926572,
CC       ECO:0000269|PubMed:22720086, ECO:0000269|PubMed:23868571,
CC       ECO:0000269|PubMed:27194766, ECO:0000269|PubMed:27282740,
CC       ECO:0000269|PubMed:27578425, ECO:0000269|PubMed:28743875,
CC       ECO:0000269|PubMed:31344133, ECO:0000269|PubMed:31801866,
CC       ECO:0000305|PubMed:11801599, ECO:0000305|PubMed:16227268,
CC       ECO:0000305|PubMed:16951545, ECO:0000305|PubMed:27676132}.
CC   -!- SUBUNIT: [RNA-directed RNA polymerase]: Homooligomer. Interacts with
CC       non-structural protein 5A (PubMed:11801599). Interacts with host VAPB
CC       (By similarity). Interacts with host PRK2/PKN2 (PubMed:15364941).
CC       Interacts with host HNRNPA1 and SEPT6; these interactions facilitate
CC       the viral replication (PubMed:17229681). Part of the replication
CC       complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA
CC       polymerase embedded in an ER-derived membranous web (PubMed:12021330,
CC       PubMed:12692249, PubMed:12692242). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000269|PubMed:11801599, ECO:0000269|PubMed:12021330,
CC       ECO:0000269|PubMed:12692242, ECO:0000269|PubMed:12692249,
CC       ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17229681}.
CC   -!- INTERACTION:
CC       P27958; P06241: FYN; Xeno; NbExp=4; IntAct=EBI-706378, EBI-515315;
CC       P27958; P62993: GRB2; Xeno; NbExp=3; IntAct=EBI-706378, EBI-401755;
CC       P27958; P08631: HCK; Xeno; NbExp=5; IntAct=EBI-706378, EBI-346340;
CC       P27958; P06240: Lck; Xeno; NbExp=3; IntAct=EBI-706378, EBI-1401;
CC       P27958; P07948: LYN; Xeno; NbExp=4; IntAct=EBI-706378, EBI-79452;
CC       PRO_0000037566; PRO_0000037566 [P27958]: -; NbExp=4; IntAct=EBI-6377335, EBI-6377335;
CC       PRO_0000037566; Q96CW1: AP2M1; Xeno; NbExp=4; IntAct=EBI-6377335, EBI-297683;
CC       PRO_0000037566; Q07021: C1QBP; Xeno; NbExp=4; IntAct=EBI-6377335, EBI-347528;
CC       PRO_0000037566; P38936: CDKN1A; Xeno; NbExp=3; IntAct=EBI-6377335, EBI-375077;
CC       PRO_0000037566; O00571: DDX3X; Xeno; NbExp=11; IntAct=EBI-6377335, EBI-353779;
CC       PRO_0000037566; P02675: FGB; Xeno; NbExp=4; IntAct=EBI-6377335, EBI-1034445;
CC       PRO_0000037566; Q16644: MAPKAPK3; Xeno; NbExp=5; IntAct=EBI-6377335, EBI-1384657;
CC       PRO_0000037566; P29590: PML; Xeno; NbExp=6; IntAct=EBI-6377335, EBI-295890;
CC       PRO_0000037566; P42224: STAT1; Xeno; NbExp=2; IntAct=EBI-6377335, EBI-1057697;
CC       PRO_0000037566; Q13625: TP53BP2; Xeno; NbExp=5; IntAct=EBI-6377335, EBI-77642;
CC       PRO_0000037566; P08670: VIM; Xeno; NbExp=4; IntAct=EBI-6377335, EBI-353844;
CC       PRO_0000037566; PRO_0000037615 [P26660]; Xeno; NbExp=4; IntAct=EBI-6377335, EBI-6875462;
CC       PRO_0000037569; PRO_0000037570 [P27958]: -; NbExp=10; IntAct=EBI-6904259, EBI-6904269;
CC       PRO_0000037569; PRO_0000037572 [P27958]: -; NbExp=2; IntAct=EBI-6904259, EBI-6919131;
CC       PRO_0000037569; P07823: HSPA5; Xeno; NbExp=3; IntAct=EBI-6904259, EBI-371776;
CC       PRO_0000037569; P02788: LTF; Xeno; NbExp=3; IntAct=EBI-6904259, EBI-1058602;
CC       PRO_0000037570; P02649: APOE; Xeno; NbExp=4; IntAct=EBI-6904269, EBI-1222467;
CC       PRO_0000037570; P60033: CD81; Xeno; NbExp=11; IntAct=EBI-6904269, EBI-712921;
CC       PRO_0000037570; Q920L9: CNX; Xeno; NbExp=2; IntAct=EBI-6904269, EBI-9209498;
CC       PRO_0000037570; P19525: EIF2AK2; Xeno; NbExp=4; IntAct=EBI-6904269, EBI-640775;
CC       PRO_0000037570; Q9Z2B5: Eif2ak3; Xeno; NbExp=5; IntAct=EBI-6904269, EBI-1226344;
CC       PRO_0000037570; P07823: HSPA5; Xeno; NbExp=3; IntAct=EBI-6904269, EBI-371776;
CC       PRO_0000037570; P02788: LTF; Xeno; NbExp=9; IntAct=EBI-6904269, EBI-1058602;
CC       PRO_0000037570; P24627: LTF; Xeno; NbExp=3; IntAct=EBI-6904269, EBI-8076910;
CC       PRO_0000037570; P11226: MBL2; Xeno; NbExp=6; IntAct=EBI-6904269, EBI-5325353;
CC       PRO_0000037570; Q8WTV0: SCARB1; Xeno; NbExp=2; IntAct=EBI-6904269, EBI-78657;
CC       PRO_0000037571; PRO_0000037572 [P27958]: -; NbExp=3; IntAct=EBI-6927261, EBI-6919131;
CC       PRO_0000037572; PRO_0000037572 [P27958]: -; NbExp=2; IntAct=EBI-6919131, EBI-6919131;
CC       PRO_0000037572; PRO_0000037573 [P27958]: -; NbExp=11; IntAct=EBI-6919131, EBI-3649474;
CC       PRO_0000037572; PRO_0000037575 [P27958]: -; NbExp=5; IntAct=EBI-6919131, EBI-8763498;
CC       PRO_0000037572; Q9UHD4: CIDEB; Xeno; NbExp=6; IntAct=EBI-6919131, EBI-7062247;
CC       PRO_0000037572; Q14164: IKBKE; Xeno; NbExp=2; IntAct=EBI-6919131, EBI-307369;
CC       PRO_0000037572; Q9UHD2: TBK1; Xeno; NbExp=2; IntAct=EBI-6919131, EBI-356402;
CC       PRO_0000037573; PRO_0000037573 [P27958]: -; NbExp=3; IntAct=EBI-3649474, EBI-3649474;
CC       PRO_0000037573; PRO_0000037574 [P27958]: -; NbExp=17; IntAct=EBI-3649474, EBI-6904374;
CC       PRO_0000037573; PRO_0000037575 [P27958]: -; NbExp=4; IntAct=EBI-3649474, EBI-8763498;
CC       PRO_0000037573; PRO_0000037577 [P27958]: -; NbExp=10; IntAct=EBI-3649474, EBI-6904388;
CC       PRO_0000037573; Q8IUD2-3: ERC1; Xeno; NbExp=8; IntAct=EBI-3649474, EBI-9352449;
CC       PRO_0000037573; Q8IUD2-4: ERC1; Xeno; NbExp=3; IntAct=EBI-3649474, EBI-9352501;
CC       PRO_0000037573; P28062: PSMB8; Xeno; NbExp=4; IntAct=EBI-3649474, EBI-372294;
CC       PRO_0000037573; P62314: SNRPD1; Xeno; NbExp=7; IntAct=EBI-3649474, EBI-372177;
CC       PRO_0000037573; Q9UHD2: TBK1; Xeno; NbExp=4; IntAct=EBI-3649474, EBI-356402;
CC       PRO_0000037574; PRO_0000037572 [P27958]: -; NbExp=6; IntAct=EBI-6904374, EBI-6919131;
CC       PRO_0000037574; PRO_0000037575 [P27958]: -; NbExp=4; IntAct=EBI-6904374, EBI-8763498;
CC       PRO_0000037574; PRO_0000037577 [P27958]: -; NbExp=8; IntAct=EBI-6904374, EBI-6904388;
CC       PRO_0000037575; PRO_0000037575 [P27958]: -; NbExp=2; IntAct=EBI-8763498, EBI-8763498;
CC       PRO_0000037575; PRO_0000037576 [P27958]: -; NbExp=7; IntAct=EBI-8763498, EBI-8753518;
CC       PRO_0000037575; PRO_0000037577 [P27958]: -; NbExp=5; IntAct=EBI-8763498, EBI-6904388;
CC       PRO_0000037575; Q99941: ATF6B; Xeno; NbExp=5; IntAct=EBI-8763498, EBI-2841031;
CC       PRO_0000037575; Q86WV6: STING1; Xeno; NbExp=5; IntAct=EBI-8763498, EBI-2800345;
CC       PRO_0000037576; PRO_0000037572 [P27958]: -; NbExp=4; IntAct=EBI-8753518, EBI-6919131;
CC       PRO_0000037576; PRO_0000037573 [P27958]: -; NbExp=8; IntAct=EBI-8753518, EBI-3649474;
CC       PRO_0000037576; PRO_0000037574 [P27958]: -; NbExp=6; IntAct=EBI-8753518, EBI-6904374;
CC       PRO_0000037576; PRO_0000037576 [P27958]: -; NbExp=2; IntAct=EBI-8753518, EBI-8753518;
CC       PRO_0000037576; Q96P48: ARAP1; Xeno; NbExp=3; IntAct=EBI-8753518, EBI-710003;
CC       PRO_0000037576; O00499: BIN1; Xeno; NbExp=11; IntAct=EBI-8753518, EBI-719094;
CC       PRO_0000037576; O00499-7: BIN1; Xeno; NbExp=2; IntAct=EBI-8753518, EBI-8870146;
CC       PRO_0000037576; Q9H6F5: CCDC86; Xeno; NbExp=3; IntAct=EBI-8753518, EBI-721289;
CC       PRO_0000037576; P29762: CRABP1; Xeno; NbExp=3; IntAct=EBI-8753518, EBI-725950;
CC       PRO_0000037576; P19525: EIF2AK2; Xeno; NbExp=5; IntAct=EBI-8753518, EBI-640775;
CC       PRO_0000037576; O00410: IPO5; Xeno; NbExp=5; IntAct=EBI-8753518, EBI-356424;
CC       PRO_0000037576; P42356: PI4KA; Xeno; NbExp=7; IntAct=EBI-8753518, EBI-723050;
CC       PRO_0000037576; P42224: STAT1; Xeno; NbExp=4; IntAct=EBI-8753518, EBI-1057697;
CC       PRO_0000037576; Q96BZ9: TBC1D20; Xeno; NbExp=11; IntAct=EBI-8753518, EBI-9254454;
CC       PRO_0000037576; P39429: Traf2; Xeno; NbExp=5; IntAct=EBI-8753518, EBI-520016;
CC       PRO_0000037576; Q9P0L0: VAPA; Xeno; NbExp=7; IntAct=EBI-8753518, EBI-1059156;
CC       PRO_0000037576; PRO_0000045592 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-8753518, EBI-6858513;
CC       PRO_0000037577; PRO_0000037572 [P27958]: -; NbExp=5; IntAct=EBI-6904388, EBI-6919131;
CC       PRO_0000037577; PRO_0000037576 [P27958]: -; NbExp=6; IntAct=EBI-6904388, EBI-8753518;
CC       PRO_0000037577; P12814: ACTN1; Xeno; NbExp=7; IntAct=EBI-6904388, EBI-351710;
CC       PRO_0000037577; Q13315: ATM; Xeno; NbExp=3; IntAct=EBI-6904388, EBI-495465;
CC       PRO_0000037577; O96017: CHEK2; Xeno; NbExp=3; IntAct=EBI-6904388, EBI-1180783;
CC       PRO_0000037577; P17844: DDX5; Xeno; NbExp=12; IntAct=EBI-6904388, EBI-351962;
CC       PRO_0000037577; Q14240: EIF4A2; Xeno; NbExp=4; IntAct=EBI-6904388, EBI-73473;
CC       PRO_0000037577; P09651: HNRNPA1; Xeno; NbExp=4; IntAct=EBI-6904388, EBI-352662;
CC       PRO_0000037577; P19338: NCL; Xeno; NbExp=4; IntAct=EBI-6904388, EBI-346967;
CC       PRO_0000037577; Q14141: SEPTIN6; Xeno; NbExp=4; IntAct=EBI-6904388, EBI-745901;
CC       PRO_0000037577; Q9P0L0: VAPA; Xeno; NbExp=5; IntAct=EBI-6904388, EBI-1059156;
CC   -!- SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic
CC       reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane
CC       protein {ECO:0000255}. Host mitochondrion membrane
CC       {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein
CC       {ECO:0000255}. Note=The C-terminal transmembrane domain of the core
CC       protein precursor contains an ER signal leading the nascent polyprotein
CC       to the ER membrane.
CC   -!- SUBCELLULAR LOCATION: [Mature core protein]: Virion
CC       {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm
CC       {ECO:0000269|PubMed:9037030}. Host nucleus
CC       {ECO:0000250|UniProtKB:P26662}. Host lipid droplet
CC       {ECO:0000269|PubMed:11706032, ECO:0000269|PubMed:9037030}. Note=Only a
CC       minor proportion of core protein is present in the nucleus
CC       (PubMed:9037030). Probably present on the surface of lipid droplets
CC       (PubMed:9037030). {ECO:0000269|PubMed:9037030}.
CC   -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane
CC       {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host
CC       endoplasmic reticulum membrane; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:10729138}. Note=The C-terminal transmembrane domain
CC       acts as a signal sequence and forms a hairpin structure before cleavage
CC       by host signal peptidase (PubMed:10729138). After cleavage, the
CC       membrane sequence is retained at the C-terminus of the protein, serving
CC       as ER membrane anchor (PubMed:10729138). A reorientation of the second
CC       hydrophobic stretch occurs after cleavage producing a single reoriented
CC       transmembrane domain (PubMed:12065403). These events explain the final
CC       topology of the protein (PubMed:12065403).
CC       {ECO:0000269|PubMed:10729138, ECO:0000269|PubMed:12065403}.
CC   -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane
CC       {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host
CC       endoplasmic reticulum membrane; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:10729138}. Host lipid droplet
CC       {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane
CC       domain acts as a signal sequence and forms a hairpin structure before
CC       cleavage by host signal peptidase (PubMed:10729138). After cleavage,
CC       the membrane sequence is retained at the C-terminus of the protein,
CC       serving as ER membrane anchor (PubMed:10729138). A reorientation of the
CC       second hydrophobic stretch occurs after cleavage producing a single
CC       reoriented transmembrane domain (PubMed:12065403). These events explain
CC       the final topology of the protein (PubMed:12065403).
CC       {ECO:0000269|PubMed:10729138, ECO:0000269|PubMed:12065403}.
CC   -!- SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum
CC       membrane {ECO:0000269|PubMed:11907211}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:11907211}. Host mitochondrion
CC       {ECO:0000269|PubMed:29039530}. Host cell membrane
CC       {ECO:0000269|PubMed:11907211, ECO:0000269|PubMed:27320856}. Note=The C-
CC       terminus of p7 membrane domain acts as a signal sequence
CC       (PubMed:11907211). After cleavage by host signal peptidase, the
CC       membrane sequence is retained at the C-terminus of the protein, serving
CC       as ER membrane anchor (PubMed:11907211). ER retention of p7 is leaky
CC       and a small fraction reaches the plasma membrane (PubMed:11907211).
CC       {ECO:0000269|PubMed:11907211}.
CC   -!- SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum
CC       membrane {ECO:0000250|UniProtKB:P26664}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P26664}. Host lipid droplet
CC       {ECO:0000250|UniProtKB:Q99IB8}. Note=Probably present on the surface of
CC       lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic
CC       reticulum membrane {ECO:0000305}; Peripheral membrane protein
CC       {ECO:0000305}. Note=NS3 is associated to the ER membrane through its
CC       binding to NS4A. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC       reticulum membrane {ECO:0000305}; Single-pass type I membrane protein
CC       {ECO:0000305}. Note=Host membrane insertion occurs after processing by
CC       the NS3 protease. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:12692244,
CC       ECO:0000269|PubMed:17030859}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:12692244}. Note=A reorientation of the N-terminus
CC       into the ER lumen occurs post-translationally (PubMed:17030859).
CC       Localized in the vicinity of host lipid droplet (PubMed:26185986).
CC       {ECO:0000269|PubMed:17030859, ECO:0000269|PubMed:26185986}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:11744739,
CC       ECO:0000269|PubMed:15247283}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:15247283, ECO:0000269|PubMed:17192310}. Host
CC       cytoplasm, host perinuclear region {ECO:0000269|PubMed:15247283}. Host
CC       mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm
CC       {ECO:0000269|PubMed:8982089}. Host nucleus
CC       {ECO:0000269|PubMed:10702287}. Host lipid droplet
CC       {ECO:0000250|UniProtKB:P26662}. Note=Host membrane insertion occurs
CC       after processing by the NS3 protease (PubMed:11744739). Localizes at
CC       the surface of lipid droplets (By similarity).
CC       {ECO:0000250|UniProtKB:P26662, ECO:0000269|PubMed:11744739}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm
CC       {ECO:0000269|PubMed:17229681}. Host endoplasmic reticulum membrane;
CC       Single-pass type IV membrane protein {ECO:0000269|PubMed:11557752}.
CC       Note=Host membrane insertion occurs after processing by the NS3
CC       protease. {ECO:0000269|PubMed:11557752}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC         Comment=The exact location of the ribosomal frameshift is unknown.
CC         The F protein seems to be generated by a -2 ribosomal frameshift
CC         located in the vicinity of codon 11 of the core protein coding
CC         sequence. However, some F proteins may also be generated by +1
CC         ribosomal frameshift. Since the core gene encodes alternative reading
CC         frame proteins (ARFPs), many functions depicted for the core protein
CC         might belong to the ARFPs. {ECO:0000269|PubMed:11447125};
CC       Name=Genome polyprotein;
CC         IsoId=P27958-1; Sequence=Displayed;
CC       Name=F protein; Synonyms=Frameshifted protein;
CC         IsoId=P0C045-1; Sequence=External;
CC   -!- INDUCTION: [Mature core protein]: Expressed late in the infection
CC       cycle. {ECO:0000269|PubMed:25351725}.
CC   -!- DOMAIN: [Mature core protein]: The disordered N-terminus allows the
CC       interaction with several host proteins (PubMed:18992225,
CC       PubMed:25424537). This disordered region also seems to play an
CC       important role in mediating RNA chaperoning (PubMed:18033802).
CC       {ECO:0000269|PubMed:18033802, ECO:0000269|PubMed:18992225,
CC       ECO:0000269|PubMed:25424537}.
CC   -!- DOMAIN: [Envelope glycoprotein E1]: The transmembrane regions of
CC       envelope E1 and E2 glycoproteins are involved in heterodimer formation,
CC       ER localization, and assembly of these proteins.
CC       {ECO:0000269|PubMed:11145889}.
CC   -!- DOMAIN: [Envelope glycoprotein E2]: The transmembrane regions of
CC       envelope E1 and E2 glycoproteins are involved in heterodimer formation,
CC       ER localization, and assembly of these proteins (PubMed:11145889).
CC       Envelope E2 glycoprotein contain two highly variable regions called
CC       hypervariable region 1 and 2 (HVR1 and HVR2) (PubMed:11356980). E2 also
CC       contain two segments involved in CD81-binding (By similarity). HVR1 is
CC       implicated in the SCARB1-mediated cell entry and probably acts as a
CC       regulator of the association of particles with lipids
CC       (PubMed:22767607). {ECO:0000250|UniProtKB:P26663,
CC       ECO:0000269|PubMed:11145889, ECO:0000269|PubMed:11356980,
CC       ECO:0000269|PubMed:22767607}.
CC   -!- DOMAIN: [Protease NS2]: The N-terminus of NS3 is required for the
CC       catalytic activity of protease NS2 (By similarity). The minimal
CC       catalytic region includes the C-terminus of NS2 and the N-terminus NS3
CC       protease domain (active region NS2-3) (By similarity).
CC       {ECO:0000250|UniProtKB:P26663}.
CC   -!- DOMAIN: [Serine protease/helicase NS3]: The N-terminal one-third
CC       contains the protease activity (By similarity). This region contains a
CC       zinc atom that does not belong to the active site, but may play a
CC       structural rather than a catalytic role (By similarity). This region is
CC       essential for the activity of protease NS2, maybe by contributing to
CC       the folding of the latter (By similarity). The NTPase/helicase activity
CC       is located in the twothirds C-terminus of NS3, this domain contains the
CC       NTPase and RNA-binding regions (PubMed:1658800).
CC       {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26663,
CC       ECO:0000269|PubMed:1658800}.
CC   -!- DOMAIN: [Non-structural protein 4B]: Contains a glycine zipper region
CC       that critically contributes to the biogenesis of functional ER-derived
CC       replication organelles. {ECO:0000250|UniProtKB:Q99IB8}.
CC   -!- DOMAIN: [Non-structural protein 5A]: The N-terminus acts as a membrane
CC       anchor (PubMed:15247283). The C-terminus contains a nuclear
CC       localization signal (PubMed:8982089). {ECO:0000269|PubMed:15247283,
CC       ECO:0000269|PubMed:8982089}.
CC   -!- DOMAIN: [Non-structural protein 5A]: Contains a variable region called
CC       interferon sensitivity determining region (ISDR) and a variable region
CC       called variable region 3 (V3) (By similarity). ISDR and V3 may be
CC       involved in sensitivity and/or resistance to IFN-alpha therapy (By
CC       similarity). {ECO:0000250|UniProtKB:P26662}.
CC   -!- DOMAIN: [Non-structural protein 5A]: The SH3-binding domain is involved
CC       in the interaction with host BIN1, GRB2 and Src-family kinases.
CC       {ECO:0000269|PubMed:16530520}.
CC   -!- DOMAIN: [Non-structural protein 5A]: The structured region D1 is
CC       involved in RNA-binding. {ECO:0000269|PubMed:20926572}.
CC   -!- DOMAIN: [Non-structural protein 5A]: The first disordered region named
CC       D2 interacts with several viral and host proteins (PubMed:27676132,
CC       PubMed:27194766). The largely disordered region D3 mediates the
CC       interaction with several host proteins and is involved in virion
CC       assembly (PubMed:22720086, PubMed:26727512, PubMed:27194766).
CC       {ECO:0000269|PubMed:22720086, ECO:0000269|PubMed:26727512,
CC       ECO:0000269|PubMed:27194766, ECO:0000269|PubMed:27676132}.
CC   -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC       mature proteins (PubMed:8189513, PubMed:15722527, PubMed:8035505,
CC       PubMed:8386278). The structural proteins, core, E1, E2 and p7 are
CC       produced by proteolytic processing by host signal peptidases
CC       (PubMed:15247249). The core protein precursor is synthesized as a 23
CC       kDa, which is retained in the ER membrane through the hydrophobic
CC       signal peptide (By similarity). Cleavage by the signal peptidase
CC       releases the 21 kDa mature core protein (By similarity). The cleavage
CC       of the core protein precursor occurs between aminoacids 176 and 188 but
CC       the exact cleavage site is not known (By similarity). Some degraded
CC       forms of the core protein appear as well during the course of infection
CC       (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and
CC       NS5B) are cleaved by the viral proteases (PubMed:15247249,
CC       PubMed:7679746, PubMed:8189513, PubMed:8035505, PubMed:8386278).
CC       Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine
CC       protease catalytic domain and regulated by the NS3 N-terminal domain
CC       (By similarity). {ECO:0000250|UniProtKB:P26663,
CC       ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:Q99IB8,
CC       ECO:0000269|PubMed:15247249, ECO:0000269|PubMed:15722527,
CC       ECO:0000269|PubMed:7679746, ECO:0000269|PubMed:8035505,
CC       ECO:0000269|PubMed:8189513, ECO:0000269|PubMed:8386278}.
CC   -!- PTM: [Mature core protein]: Phosphorylated by host PKC and PKA.
CC       {ECO:0000250|UniProtKB:Q01403}.
CC   -!- PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and
CC       leading to core protein subsequent proteasomal degradation.
CC       {ECO:0000250|UniProtKB:Q03463}.
CC   -!- PTM: [Envelope glycoprotein E1]: Highly N-glycosylated.
CC       {ECO:0000269|PubMed:14990718}.
CC   -!- PTM: [Envelope glycoprotein E2]: Highly N-glycosylated.
CC       {ECO:0000269|PubMed:14990718, ECO:0000269|PubMed:18187336}.
CC   -!- PTM: [Protease NS2]: Palmitoylation is required for NS2/3
CC       autoprocessing and E2 recruitment to membranes.
CC       {ECO:0000269|PubMed:31597774}.
CC   -!- PTM: [Non-structural protein 4B]: Palmitoylated. This modification may
CC       play a role in its polymerization or in protein-protein interactions.
CC       {ECO:0000269|PubMed:16731940}.
CC   -!- PTM: [Non-structural protein 5A]: Cleaved by host caspases which are
CC       probably activated by the viral infection.
CC       {ECO:0000250|UniProtKB:P26662}.
CC   -!- PTM: [Non-structural protein 5A]: Ubiquitinated (PubMed:27194766,
CC       PubMed:25683609). Ubiquitination, most probably at Lys-2350, mediated
CC       by host IFI27 and SKP2 leads to proteasomal degradation, restricting
CC       viral infection (PubMed:27194766). Ubiquitination by host TRIM22 leads
CC       to interruption of viral replication (PubMed:25683609).
CC       {ECO:0000269|PubMed:25683609, ECO:0000269|PubMed:27194766}.
CC   -!- PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal
CC       form termed p56 (By similarity). p58 is a hyperphosphorylated form of
CC       p56 (By similarity). p56 and p58 coexist in the cell in roughly
CC       equivalent amounts (By similarity). Hyperphosphorylation is dependent
CC       on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha, PI4KA
CC       or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By
CC       similarity). Phosphorylated NS5A is involved in viral replication (By
CC       similarity). {ECO:0000250|UniProtKB:P26662,
CC       ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q99IB8}.
CC   -!- PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential
CC       for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.
CC   -!- PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by
CC       host PRK2/PKN2. {ECO:0000269|PubMed:15364941}.
CC   -!- MISCELLANEOUS: Viral particle assembly takes place at the surface of
CC       ER-derived membranes in close proximity to lipid droplets. NS2
CC       associates with E1/E2 glycoproteins, NS3 and NS5A, which interacts with
CC       the viral RNA and core protein to promote genome encapsidation. The
CC       nucleocapsid buds at the ER membrane where E1/E2 glycoproteins are
CC       anchored and afterward associate with nascent lipid droplet to acquire
CC       APOE and APOC. Secretion of viral particles is probably regulated by
CC       viroporin p7. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Non-structural protein 5A]: Cell culture adaptation of
CC       the virus leads to mutations in NS5A, reducing its inhibitory effect on
CC       replication. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Mature core protein]: Exerts viral interference on
CC       hepatitis B virus when HCV and HBV coinfect the same cell, by
CC       suppressing HBV gene expression, RNA encapsidation and budding.
CC       {ECO:0000250|UniProtKB:P26662}.
CC   -!- SIMILARITY: Belongs to the hepacivirus polyprotein family.
CC       {ECO:0000305}.
CC   -!- CAUTION: The core gene probably also codes for alternative reading
CC       frame proteins (ARFPs). Many functions depicted for the core protein
CC       might belong to the ARFPs. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC       URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_hcv";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M67463; AAA45534.1; -; Genomic_RNA.
DR   EMBL; AF009606; AAB66324.1; -; Genomic_RNA.
DR   EMBL; AF011751; AAB67036.1; -; Genomic_RNA.
DR   EMBL; AF011752; AAB67037.1; -; Genomic_RNA.
DR   EMBL; AF011753; AAB67038.1; -; Genomic_RNA.
DR   PIR; A36814; GNWVCH.
DR   PDB; 1A1R; X-ray; 2.50 A; A/B=1027-1206.
DR   PDB; 1A1V; X-ray; 2.20 A; A=1193-1657.
DR   PDB; 1CWX; NMR; -; A=2-45.
DR   PDB; 1HEI; X-ray; 2.10 A; A/B=1206-1656.
DR   PDB; 1JR6; NMR; -; A=1353-1456, A=1478-1507.
DR   PDB; 1N1L; X-ray; 2.60 A; A/B=1027-1206.
DR   PDB; 1ONB; NMR; -; A=1353-1456, A=1478-1507.
DR   PDB; 1R7C; NMR; -; A=1973-2003.
DR   PDB; 1R7D; NMR; -; A=1973-2003.
DR   PDB; 1R7E; NMR; -; A=1973-2003.
DR   PDB; 1R7F; NMR; -; A=1973-2003.
DR   PDB; 1R7G; NMR; -; A=1973-2003.
DR   PDB; 1RGQ; X-ray; 2.90 A; A/B=1027-1207.
DR   PDB; 2A4R; X-ray; 2.40 A; A/C=1027-1207, B/D=1680-1696.
DR   PDB; 2F9V; X-ray; 2.60 A; A/C=1027-1207, B/D=1678-1696.
DR   PDB; 2HD0; X-ray; 2.28 A; A/B/C/D/E/F/G/H/I/J/K/L=903-1026.
DR   PDB; 2JXF; NMR; -; A=1751-1780.
DR   PDB; 2KDR; NMR; -; X=1938-1965.
DR   PDB; 2N1P; NMR; -; A=2982-3011.
DR   PDB; 2O8M; X-ray; 2.00 A; A/B=1027-1207, C/D=1678-1696.
DR   PDB; 2OBO; X-ray; 2.60 A; A/C=1022-1207, B/D=1677-1695.
DR   PDB; 2OBQ; X-ray; 2.50 A; A/C=1027-1207, B/D=1678-1696.
DR   PDB; 2OC0; X-ray; 2.30 A; A/C=1027-1207, B/D=1680-1696.
DR   PDB; 2OC1; X-ray; 2.70 A; A/C=1027-1207, B/D=1680-1696.
DR   PDB; 2OC7; X-ray; 2.70 A; A/C=1027-1207, B/D=1680-1696.
DR   PDB; 2OC8; X-ray; 2.66 A; A/C=1027-1207, B/D=1680-1696.
DR   PDB; 2OIN; X-ray; 2.50 A; A/B=1027-1207, C/D=1678-1696.
DR   PDB; 2P59; X-ray; 2.90 A; C/D=1678-1696.
DR   PDB; 2QV1; X-ray; 2.40 A; C/D=1678-1696.
DR   PDB; 2XI2; X-ray; 1.80 A; A/B/C=2421-2990.
DR   PDB; 2XI3; X-ray; 1.70 A; A/B=2421-2990.
DR   PDB; 2XNI; X-ray; 3.30 A; A/B=1027-1206.
DR   PDB; 3RC4; X-ray; 1.50 A; A=1026-1208.
DR   PDB; 3RC5; X-ray; 1.60 A; A=1026-1208.
DR   PDB; 4CL1; X-ray; 3.50 A; A/B/C/D=2005-2174.
DR   PDB; 4JZN; X-ray; 2.05 A; K=434-446.
DR   PDB; 4JZO; X-ray; 2.22 A; I/J/K/L=434-446.
DR   PDB; 4MWF; X-ray; 2.64 A; C/D=412-459, C/D=486-645.
DR   PDB; 4N0Y; X-ray; 1.75 A; A=314-324.
DR   PDB; 4Q0X; X-ray; 2.90 A; E=421-446.
DR   PDB; 4XVJ; X-ray; 2.00 A; A=412-423.
DR   PDB; 4Z0X; X-ray; 2.00 A; C=435-446.
DR   PDB; 5EOC; X-ray; 1.98 A; P/Q=412-422.
DR   PDB; 5ERW; X-ray; 2.90 A; C=434-446.
DR   PDB; 5FGB; X-ray; 1.65 A; F/G=405-425.
DR   PDB; 5FGC; X-ray; 1.90 A; A=405-425.
DR   PDB; 5JZI; X-ray; 2.50 A; C/H=1406-1415.
DR   PDB; 5YXN; X-ray; 2.03 A; I=1406-1415.
DR   PDB; 5YXU; X-ray; 2.70 A; I/J=1406-1415.
DR   PDB; 6BQJ; X-ray; 1.69 A; A/B/C=1030-1208.
DR   PDB; 6BQK; X-ray; 1.97 A; A/B=1030-1208.
DR   PDB; 6BZU; X-ray; 2.70 A; I/J/K/L=412-423.
DR   PDB; 6BZV; X-ray; 2.65 A; I/J/K/L=412-423.
DR   PDB; 6BZW; X-ray; 2.20 A; I/J/K/L=412-423.
DR   PDB; 6BZY; X-ray; 1.60 A; B=412-423.
DR   PDB; 6UYD; X-ray; 1.90 A; E/F=412-645.
DR   PDB; 6WO5; X-ray; 2.62 A; E/F=412-645.
DR   PDB; 6WOQ; X-ray; 3.67 A; E/F=412-645.
DR   PDB; 7DUU; X-ray; 2.51 A; C=1254-1262.
DR   PDBsum; 1A1R; -.
DR   PDBsum; 1A1V; -.
DR   PDBsum; 1CWX; -.
DR   PDBsum; 1HEI; -.
DR   PDBsum; 1JR6; -.
DR   PDBsum; 1N1L; -.
DR   PDBsum; 1ONB; -.
DR   PDBsum; 1R7C; -.
DR   PDBsum; 1R7D; -.
DR   PDBsum; 1R7E; -.
DR   PDBsum; 1R7F; -.
DR   PDBsum; 1R7G; -.
DR   PDBsum; 1RGQ; -.
DR   PDBsum; 2A4R; -.
DR   PDBsum; 2F9V; -.
DR   PDBsum; 2HD0; -.
DR   PDBsum; 2JXF; -.
DR   PDBsum; 2KDR; -.
DR   PDBsum; 2N1P; -.
DR   PDBsum; 2O8M; -.
DR   PDBsum; 2OBO; -.
DR   PDBsum; 2OBQ; -.
DR   PDBsum; 2OC0; -.
DR   PDBsum; 2OC1; -.
DR   PDBsum; 2OC7; -.
DR   PDBsum; 2OC8; -.
DR   PDBsum; 2OIN; -.
DR   PDBsum; 2P59; -.
DR   PDBsum; 2QV1; -.
DR   PDBsum; 2XI2; -.
DR   PDBsum; 2XI3; -.
DR   PDBsum; 2XNI; -.
DR   PDBsum; 3RC4; -.
DR   PDBsum; 3RC5; -.
DR   PDBsum; 4CL1; -.
DR   PDBsum; 4JZN; -.
DR   PDBsum; 4JZO; -.
DR   PDBsum; 4MWF; -.
DR   PDBsum; 4N0Y; -.
DR   PDBsum; 4Q0X; -.
DR   PDBsum; 4XVJ; -.
DR   PDBsum; 4Z0X; -.
DR   PDBsum; 5EOC; -.
DR   PDBsum; 5ERW; -.
DR   PDBsum; 5FGB; -.
DR   PDBsum; 5FGC; -.
DR   PDBsum; 5JZI; -.
DR   PDBsum; 5YXN; -.
DR   PDBsum; 5YXU; -.
DR   PDBsum; 6BQJ; -.
DR   PDBsum; 6BQK; -.
DR   PDBsum; 6BZU; -.
DR   PDBsum; 6BZV; -.
DR   PDBsum; 6BZW; -.
DR   PDBsum; 6BZY; -.
DR   PDBsum; 6UYD; -.
DR   PDBsum; 6WO5; -.
DR   PDBsum; 6WOQ; -.
DR   PDBsum; 7DUU; -.
DR   BMRB; P27958; -.
DR   SMR; P27958; -.
DR   ELM; P27958; -.
DR   IntAct; P27958; 234.
DR   BindingDB; P27958; -.
DR   ChEMBL; CHEMBL3638344; -.
DR   DrugBank; DB08644; {1-[2-(1-FORMYL-PROPYL)-3-METHANESULFONYLAMINO-PYRROLIDINE-1-CARBONYL]-2-METHYL-PROPYL}-CARBAMIC ACID TERT-BUTYL ESTER.
DR   DrugCentral; P27958; -.
DR   MEROPS; S29.001; -.
DR   GlyGen; P27958; 15 sites, 14 N-linked glycans (11 sites).
DR   iPTMnet; P27958; -.
DR   SwissPalm; P27958; -.
DR   ABCD; P27958; 29 sequenced antibodies.
DR   euHCVdb; AF009606; -.
DR   euHCVdb; AF011751; -.
DR   euHCVdb; AF011752; -.
DR   euHCVdb; AF011753; -.
DR   euHCVdb; M67463; -.
DR   BRENDA; 3.4.21.98; 17003.
DR   Reactome; R-HSA-8854214; TBC/RABGAPs.
DR   EvolutionaryTrace; P27958; -.
DR   Proteomes; UP000000518; Segment.
DR   Proteomes; UP000115192; Genome.
DR   Proteomes; UP000180556; Genome.
DR   Proteomes; UP000180557; Genome.
DR   Proteomes; UP000180558; Genome.
DR   GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044186; C:host cell lipid droplet; IEA:UniProtKB-SubCell.
DR   GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0019013; C:viral nucleocapsid; 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:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0019900; F:kinase binding; IDA:AgBase.
DR   GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IDA:DisProt.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0035663; F:Toll-like receptor 2 binding; IMP:AgBase.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0098671; P:adhesion receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039563; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039527; P:disruption by virus of host TRAF-mediated signal transduction; IEA:UniProtKB-KW.
DR   GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0019054; P:modulation by virus of host cellular process; IDA:CACAO.
DR   GO; GO:0050709; P:negative regulation of protein secretion; IDA:AgBase.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:AgBase.
DR   GO; GO:0039645; P:perturbation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR   GO; GO:0032467; P:positive regulation of cytokinesis; IMP:AgBase.
DR   GO; GO:1903301; P:positive regulation of hexokinase activity; IDA:CACAO.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IDA:AgBase.
DR   GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR   GO; GO:0019087; P:transformation of host cell by virus; IEA:InterPro.
DR   GO; GO:0044053; P:translocation of peptides or proteins into host cell cytoplasm; IMP:AgBase.
DR   GO; GO:0019069; P:viral capsid assembly; IDA:DisProt.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
DR   CDD; cd17931; DEXHc_viral_Ns3; 1.
DR   CDD; cd20903; HCV_p7; 1.
DR   CDD; cd23202; Hepacivirus_RdRp; 1.
DR   DisProt; DP00588; -.
DR   Gene3D; 2.40.10.120; -; 1.
DR   Gene3D; 3.30.70.270; -; 2.
DR   Gene3D; 6.10.250.1610; -; 1.
DR   Gene3D; 6.10.250.1750; -; 1.
DR   Gene3D; 6.10.250.2920; -; 1.
DR   Gene3D; 2.20.25.210; Hepatitis C NS5A, domain 1B; 1.
DR   Gene3D; 3.30.160.890; Hepatitis C virus envelope glycoprotein E1, chain C; 1.
DR   Gene3D; 2.30.30.710; Hepatitis C virus non-structural protein NS2, C-terminal domain; 1.
DR   Gene3D; 1.20.1280.150; Hepatitis C virus non-structural protein NS2, N-terminal domain; 1.
DR   Gene3D; 2.20.25.220; Hepatitis C virus NS5A, 1B domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 1.10.820.10; RNA Helicase Chain A , domain 3; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR011492; Flavi_DEAD.
DR   InterPro; IPR002521; HCV_Core_C.
DR   InterPro; IPR044896; HCV_core_chain_A.
DR   InterPro; IPR002522; HCV_core_N.
DR   InterPro; IPR002519; HCV_Env.
DR   InterPro; IPR002531; HCV_NS1.
DR   InterPro; IPR002518; HCV_NS2.
DR   InterPro; IPR042205; HCV_NS2_C.
DR   InterPro; IPR042209; HCV_NS2_N.
DR   InterPro; IPR000745; HCV_NS4a.
DR   InterPro; IPR001490; HCV_NS4b.
DR   InterPro; IPR002868; HCV_NS5a.
DR   InterPro; IPR013192; HCV_NS5A_1a.
DR   InterPro; IPR013193; HCV_NS5a_1B_dom.
DR   InterPro; IPR038568; HCV_NS5A_1B_sf.
DR   InterPro; IPR024350; HCV_NS5a_C.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR004109; HepC_NS3_protease.
DR   InterPro; IPR038170; NS5A_1a_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR002166; RNA_pol_HCV.
DR   Pfam; PF07652; Flavi_DEAD; 1.
DR   Pfam; PF01543; HCV_capsid; 1.
DR   Pfam; PF01542; HCV_core; 1.
DR   Pfam; PF01539; HCV_env; 1.
DR   Pfam; PF01560; HCV_NS1; 1.
DR   Pfam; PF01538; HCV_NS2; 1.
DR   Pfam; PF01006; HCV_NS4a; 1.
DR   Pfam; PF01001; HCV_NS4b; 1.
DR   Pfam; PF01506; HCV_NS5a; 1.
DR   Pfam; PF08300; HCV_NS5a_1a; 1.
DR   Pfam; PF08301; HCV_NS5a_1b; 1.
DR   Pfam; PF12941; HCV_NS5a_C; 1.
DR   Pfam; PF02907; Peptidase_S29; 1.
DR   Pfam; PF00998; RdRP_3; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SMART; SM00490; HELICc; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51693; HCV_NS2_PRO; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
DR   PROSITE; PS51822; HV_PV_NS3_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activation of host autophagy by virus;
KW   Apoptosis; ATP-binding; Capsid protein;
KW   Clathrin-mediated endocytosis of virus by host; Direct protein sequencing;
KW   Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane;
KW   G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein;
KW   Helicase; Host cell membrane; Host cytoplasm; Host endoplasmic reticulum;
KW   Host lipid droplet; Host membrane; Host mitochondrion; 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 MAVS by virus; Inhibition of host RLR pathway by virus;
KW   Inhibition of host STAT1 by virus; Inhibition of host TRAFs by virus;
KW   Interferon antiviral system evasion; Ion channel; Ion transport;
KW   Isopeptide bond; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW   Modulation of host cell cycle by virus; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Oncogene; Palmitate;
KW   Phosphoprotein; Protease; Reference proteome; Ribonucleoprotein;
KW   Ribosomal frameshifting; RNA-binding; RNA-directed RNA polymerase;
KW   Serine protease; SH3-binding; Thiol protease; Transcription;
KW   Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW   Transport; Ubl conjugation; Viral attachment to host adhesion receptor;
KW   Viral attachment to host cell; Viral attachment to host entry receptor;
KW   Viral envelope protein; Viral immunoevasion; Viral ion channel;
KW   Viral nucleoprotein; Viral penetration into host cytoplasm;
KW   Viral RNA replication; Virion; Virus endocytosis by host;
KW   Virus entry into host cell; Zinc.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P26664"
FT   CHAIN           2..3011
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000450854"
FT   CHAIN           2..191
FT                   /note="Core protein precursor"
FT                   /id="PRO_0000037566"
FT   CHAIN           2..177
FT                   /note="Mature core protein"
FT                   /id="PRO_0000037567"
FT   PROPEP          178..191
FT                   /note="ER anchor for the core protein, removed in mature
FT                   form by host signal peptidase"
FT                   /evidence="ECO:0000269|PubMed:12065403"
FT                   /id="PRO_0000037568"
FT   CHAIN           192..383
FT                   /note="Envelope glycoprotein E1"
FT                   /id="PRO_0000037569"
FT   CHAIN           384..746
FT                   /note="Envelope glycoprotein E2"
FT                   /id="PRO_0000037570"
FT   CHAIN           747..809
FT                   /note="Viroporin p7"
FT                   /id="PRO_0000037571"
FT   CHAIN           810..1026
FT                   /note="Protease NS2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT                   /id="PRO_0000037572"
FT   CHAIN           1027..1657
FT                   /note="Serine protease/helicase NS3"
FT                   /id="PRO_0000037573"
FT   CHAIN           1658..1711
FT                   /note="Non-structural protein 4A"
FT                   /id="PRO_0000037574"
FT   CHAIN           1712..1972
FT                   /note="Non-structural protein 4B"
FT                   /id="PRO_0000037575"
FT   CHAIN           1973..2420
FT                   /note="Non-structural protein 5A"
FT                   /id="PRO_0000037576"
FT   CHAIN           2421..3011
FT                   /note="RNA-directed RNA polymerase"
FT                   /id="PRO_0000037577"
FT   TOPO_DOM        2..168
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        169..189
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        190..358
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:12065403"
FT   TRANSMEM        359..379
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:12065403"
FT   TOPO_DOM        380..725
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:12065403"
FT   TRANSMEM        726..746
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:12065403"
FT   TOPO_DOM        747..757
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:11907211,
FT                   ECO:0000305|PubMed:15722527"
FT   TRANSMEM        758..778
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:11907211,
FT                   ECO:0000305|PubMed:15722527"
FT   TOPO_DOM        779..781
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:11907211,
FT                   ECO:0000305|PubMed:15722527"
FT   TRANSMEM        782..803
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:11907211,
FT                   ECO:0000305|PubMed:15722527"
FT   TOPO_DOM        804..813
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:11907211,
FT                   ECO:0000305|PubMed:15722527"
FT   TRANSMEM        814..834
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TOPO_DOM        835..838
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TRANSMEM        839..859
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TOPO_DOM        860..881
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TRANSMEM        882..902
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TOPO_DOM        903..1657
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   TRANSMEM        1658..1678
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1679..1805
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1806..1824
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1825..1828
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:17030859"
FT   TRANSMEM        1829..1849
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1850
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1851..1871
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1872..1881
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1882..1902
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1903..1972
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1973..2003
FT                   /evidence="ECO:0000269|PubMed:15247283,
FT                   ECO:0000305|PubMed:11744739"
FT   TOPO_DOM        2004..2990
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11557752"
FT   TRANSMEM        2991..3011
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:11557752"
FT   DOMAIN          899..1026
FT                   /note="Peptidase C18"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   DOMAIN          1027..1208
FT                   /note="Peptidase S29"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   DOMAIN          1217..1369
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          2634..2752
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          2..75
FT                   /note="Disordered"
FT                   /evidence="ECO:0000269|PubMed:18992225,
FT                   ECO:0000305|PubMed:18033802"
FT   REGION          2..59
FT                   /note="Interaction with DDX3X"
FT                   /evidence="ECO:0000250|UniProtKB:Q5EG65"
FT   REGION          2..58
FT                   /note="Interaction with EIF2AK2/PKR"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          2..23
FT                   /note="Interaction with STAT1"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          112..152
FT                   /note="Important for endoplasmic reticulum and
FT                   mitochondrial localization"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          122..173
FT                   /note="Interaction with APOA2"
FT                   /evidence="ECO:0000250|UniProtKB:P29846"
FT   REGION          164..167
FT                   /note="Important for lipid droplets localization"
FT                   /evidence="ECO:0000269|PubMed:11706032"
FT   REGION          265..296
FT                   /note="Important for fusion"
FT                   /evidence="ECO:0000269|PubMed:16533059"
FT   REGION          385..411
FT                   /note="HVR1"
FT                   /evidence="ECO:0000269|PubMed:11356980"
FT   REGION          474..479
FT                   /note="HVR2"
FT                   /evidence="ECO:0000269|PubMed:11356980"
FT   REGION          480..493
FT                   /note="CD81-binding 1"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   REGION          544..551
FT                   /note="CD81-binding 2"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   REGION          660..671
FT                   /note="EIF2AK2/eIF2-alpha phosphorylation homology domain
FT                   (PePHD)"
FT   REGION          904..1206
FT                   /note="Protease NS2-3"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   REGION          929..949
FT                   /note="Interaction with host SCPS1"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   REGION          1486..1497
FT                   /note="RNA-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   REGION          1679..1690
FT                   /note="NS3-binding"
FT                   /evidence="ECO:0000269|PubMed:7769699,
FT                   ECO:0000269|PubMed:8861917"
FT   REGION          1833..1861
FT                   /note="Glycine zipper"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   REGION          1978..1998
FT                   /note="Membrane-binding"
FT                   /evidence="ECO:0000269|PubMed:15247283"
FT   REGION          2005..2221
FT                   /note="D1; RNA-binding"
FT                   /evidence="ECO:0000269|PubMed:20926572"
FT   REGION          2120..2332
FT                   /note="Transcriptional activation"
FT                   /evidence="ECO:0000255"
FT   REGION          2120..2208
FT                   /note="FKBP8-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          2135..2139
FT                   /note="Interaction with non-structural protein 4A"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          2189..2441
FT                   /note="Interaction with host SKP2"
FT                   /evidence="ECO:0000305|PubMed:27194766"
FT   REGION          2210..2275
FT                   /note="Interaction with EIF2AK2/PKR"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   REGION          2210..2249
FT                   /note="ISDR"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   REGION          2223..2315
FT                   /note="D2"
FT                   /evidence="ECO:0000305|PubMed:27676132"
FT   REGION          2224..2315
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:27676132"
FT   REGION          2249..2306
FT                   /note="NS4B-binding"
FT                   /evidence="ECO:0000255"
FT   REGION          2281..2297
FT                   /note="Interaction with human PPIA/CYPA"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   REGION          2329..2420
FT                   /note="D3"
FT                   /evidence="ECO:0000305|PubMed:22720086"
FT   REGION          2332..2441
FT                   /note="Interaction with host IFI27"
FT                   /evidence="ECO:0000305|PubMed:27194766"
FT   REGION          2346..2409
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2354..2377
FT                   /note="V3"
FT   REGION          2367..2417
FT                   /note="Interaction with host VAPB"
FT                   /evidence="ECO:0000269|PubMed:22720086"
FT   MOTIF           5..13
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOTIF           38..43
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOTIF           58..64
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOTIF           66..71
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOTIF           1316..1319
FT                   /note="DECH box"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOTIF           2322..2325
FT                   /note="SH3-binding"
FT                   /evidence="ECO:0000255"
FT   MOTIF           2326..2334
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   COMPBIAS        47..69
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2312..2329
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2346..2374
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        952
FT                   /note="For protease NS2 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030,
FT                   ECO:0000269|PubMed:16862121, ECO:0000269|PubMed:8248148"
FT   ACT_SITE        972
FT                   /note="For protease NS2 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   ACT_SITE        993
FT                   /note="For protease NS2 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030,
FT                   ECO:0000269|PubMed:16862121, ECO:0000269|PubMed:8248148"
FT   ACT_SITE        1083
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:8386278, ECO:0000305|PubMed:8861917"
FT   ACT_SITE        1107
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000305|PubMed:8861917"
FT   ACT_SITE        1165
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:8248148, ECO:0000269|PubMed:8386278,
FT                   ECO:0000305|PubMed:8861917"
FT   BINDING         1123
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural; for NS3 protease activity and
FT                   NS2/3 auto-cleavage activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:21507982, ECO:0007744|PDB:1A1R,
FT                   ECO:0007744|PDB:1N1L, ECO:0007744|PDB:1RGQ,
FT                   ECO:0007744|PDB:2A4R, ECO:0007744|PDB:2F9V,
FT                   ECO:0007744|PDB:2O8M, ECO:0007744|PDB:2OBQ,
FT                   ECO:0007744|PDB:2OC0, ECO:0007744|PDB:2OC1,
FT                   ECO:0007744|PDB:2OC7, ECO:0007744|PDB:2OC8,
FT                   ECO:0007744|PDB:2OIN, ECO:0007744|PDB:2XNI"
FT   BINDING         1125
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural; for NS3 protease activity and
FT                   NS2/3 auto-cleavage activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:21507982, ECO:0007744|PDB:1A1R,
FT                   ECO:0007744|PDB:1N1L, ECO:0007744|PDB:1RGQ,
FT                   ECO:0007744|PDB:2A4R, ECO:0007744|PDB:2F9V,
FT                   ECO:0007744|PDB:2O8M, ECO:0007744|PDB:2OBQ,
FT                   ECO:0007744|PDB:2OC0, ECO:0007744|PDB:2OC1,
FT                   ECO:0007744|PDB:2OC7, ECO:0007744|PDB:2OC8,
FT                   ECO:0007744|PDB:2OIN, ECO:0007744|PDB:2XNI"
FT   BINDING         1171
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural; for NS3 protease activity and
FT                   NS2/3 auto-cleavage activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:21507982, ECO:0007744|PDB:1N1L,
FT                   ECO:0007744|PDB:1RGQ, ECO:0007744|PDB:2A4R,
FT                   ECO:0007744|PDB:2F9V, ECO:0007744|PDB:2O8M,
FT                   ECO:0007744|PDB:2OBQ, ECO:0007744|PDB:2OC0,
FT                   ECO:0007744|PDB:2OC1, ECO:0007744|PDB:2OC7,
FT                   ECO:0007744|PDB:2OC8, ECO:0007744|PDB:2OIN,
FT                   ECO:0007744|PDB:2XNI"
FT   BINDING         1175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural; for NS3 protease activity and
FT                   NS2/3 auto-cleavage activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT                   ECO:0000269|PubMed:21507982"
FT   BINDING         1230..1237
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   BINDING         1237
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic; for NS3 helicase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         1317
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic; for NS3 helicase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         2011
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         2029
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         2031
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         2052
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT   BINDING         2640
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   BINDING         2738
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   BINDING         2739
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P26663"
FT   SITE            177..178
FT                   /note="Cleavage; by host signal peptide peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   SITE            191..192
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   SITE            383..384
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   SITE            746..747
FT                   /note="Cleavage; by host signal peptidase"
FT   SITE            809..810
FT                   /note="Cleavage; by host signal peptidase"
FT   SITE            1026..1027
FT                   /note="Cleavage; by protease NS2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   SITE            1657..1658
FT                   /note="Cleavage; by serine protease/helicase NS3"
FT                   /evidence="ECO:0000269|PubMed:8386278"
FT   SITE            1711..1712
FT                   /note="Cleavage; by serine protease/helicase NS3"
FT                   /evidence="ECO:0000269|PubMed:8386278"
FT   SITE            1972..1973
FT                   /note="Cleavage; by serine protease/helicase NS3"
FT                   /evidence="ECO:0000269|PubMed:8386278"
FT   SITE            2420..2421
FT                   /note="Cleavage; by serine protease/helicase NS3"
FT                   /evidence="ECO:0000269|PubMed:8386278"
FT   MOD_RES         2
FT                   /note="N-acetylserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q913V3"
FT   MOD_RES         53
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q01403"
FT   MOD_RES         99
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q01403"
FT   MOD_RES         116
FT                   /note="Phosphoserine; by host PKA"
FT                   /evidence="ECO:0000250|UniProtKB:Q01403"
FT   MOD_RES         2194
FT                   /note="Phosphoserine; by host; in p56"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOD_RES         2197
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   MOD_RES         2201
FT                   /note="Phosphoserine; by host; in p56 and p58, regulates
FT                   intracellular NS5A distribution"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOD_RES         2204
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOD_RES         2207
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOD_RES         2210
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250|UniProtKB:Q99IB8"
FT   MOD_RES         2321
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000269|PubMed:10488152"
FT   MOD_RES         2449
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   MOD_RES         2462
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P26662"
FT   LIPID           922
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000269|PubMed:31597774"
FT   LIPID           1968
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000269|PubMed:16731940"
FT   LIPID           1972
FT                   /note="S-palmitoyl cysteine; by host; partial"
FT                   /evidence="ECO:0000269|PubMed:16731940"
FT   CARBOHYD        196
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000269|PubMed:10211957"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000269|PubMed:10211957"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000269|PubMed:10211957"
FT   CARBOHYD        305
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000269|PubMed:10211957"
FT   CARBOHYD        417
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        423
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        430
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336,
FT                   ECO:0000269|PubMed:24288331"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        476
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        532
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336,
FT                   ECO:0000269|PubMed:24288331"
FT   CARBOHYD        540
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        556
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336,
FT                   ECO:0000269|PubMed:24288331"
FT   CARBOHYD        576
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336,
FT                   ECO:0000269|PubMed:24288331"
FT   CARBOHYD        645
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000269|PubMed:18187336"
FT   DISULFID        429..552
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        452..459
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        486..494
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        503..508
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        564..569
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        581..585
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        597..620
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        607..644
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   DISULFID        652..677
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   CROSSLNK        2350
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000305|PubMed:27194766"
FT   VARIANT         212
FT                   /note="V -> I (in strain: Isolate H77)"
FT   VARIANT         297
FT                   /note="H -> R (in strain: Isolate H77)"
FT   VARIANT         303
FT                   /note="D -> S (in strain: Isolate H77)"
FT   VARIANT         321
FT                   /note="N -> D (in strain: Isolate H77)"
FT   VARIANT         360
FT                   /note="K -> A (in strain: Isolate H77)"
FT   VARIANT         391
FT                   /note="N -> S (in strain: Isolate H77)"
FT   VARIANT         394
FT                   /note="R -> H (in strain: Isolate H77)"
FT   VARIANT         431
FT                   /note="E -> D (in strain: Isolate H77)"
FT   VARIANT         434
FT                   /note="N -> T (in strain: Isolate H77)"
FT   VARIANT         444
FT                   /note="Q -> R (in strain: Isolate H77)"
FT   VARIANT         457
FT                   /note="A -> T (in strain: Isolate H77)"
FT   VARIANT         564..566
FT                   /note="CGA -> RGV (in strain: Isolate H77)"
FT   VARIANT         589
FT                   /note="Y -> H (in strain: Isolate H77)"
FT   VARIANT         602
FT                   /note="R -> W (in strain: Isolate H77)"
FT   VARIANT         650
FT                   /note="E -> G (in strain: Isolate H77)"
FT   VARIANT         773
FT                   /note="C -> R (in strain: Isolate H77)"
FT   VARIANT         787
FT                   /note="V -> A (in strain: Isolate H77)"
FT   VARIANT         790
FT                   /note="L -> F (in strain: Isolate H77)"
FT   VARIANT         877
FT                   /note="T -> M (in strain: Isolate H77)"
FT   VARIANT         883
FT                   /note="A -> T (in strain: Isolate H77)"
FT   VARIANT         948
FT                   /note="C -> Y (in strain: Isolate H77)"
FT   VARIANT         954
FT                   /note="A -> T (in strain: Isolate H77)"
FT   VARIANT         1026
FT                   /note="L -> Q (in strain: Isolate H77)"
FT   VARIANT         1033
FT                   /note="A -> T (in strain: Isolate H77)"
FT   VARIANT         1049
FT                   /note="G -> S (in strain: Isolate H77)"
FT   VARIANT         1100
FT                   /note="T -> M (in strain: Isolate H77)"
FT   VARIANT         1121
FT                   /note="T -> A (in strain: Isolate H77)"
FT   VARIANT         1173
FT                   /note="T -> A (in strain: Isolate H77)"
FT   VARIANT         1202
FT                   /note="E -> G (in strain: Isolate H77)"
FT   VARIANT         1214
FT                   /note="S -> P (in strain: Isolate H77)"
FT   VARIANT         1247
FT                   /note="K -> Q (in strain: Isolate H77)"
FT   VARIANT         1303
FT                   /note="A -> G (in strain: Isolate H77)"
FT   VARIANT         1327
FT                   /note="S -> L (in strain: Isolate H77)"
FT   VARIANT         1556
FT                   /note="G -> E (in strain: Isolate H77)"
FT   VARIANT         1608
FT                   /note="R -> W (in strain: Isolate H77)"
FT   VARIANT         1742
FT                   /note="H -> Q (in strain: Isolate H77)"
FT   VARIANT         1839..1840
FT                   /note="LD -> IG (in strain: Isolate H77)"
FT   VARIANT         1893
FT                   /note="A -> V (in strain: Isolate H77)"
FT   VARIANT         1898..1900
FT                   /note="FAS -> CAA (in strain: Isolate H77)"
FT   VARIANT         1905
FT                   /note="R -> H (in strain: Isolate H77)"
FT   VARIANT         1940
FT                   /note="A -> V (in strain: Isolate H77)"
FT   VARIANT         2043
FT                   /note="T -> A (in strain: Isolate H77)"
FT   VARIANT         2053
FT                   /note="K -> R (in strain: Isolate H77)"
FT   VARIANT         2061
FT                   /note="F -> L (in strain: Isolate H77)"
FT   VARIANT         2102
FT                   /note="V -> I (in strain: Isolate H77)"
FT   VARIANT         2185
FT                   /note="A -> E (in strain: Isolate H77)"
FT   VARIANT         2283
FT                   /note="P -> R (in strain: Isolate H77)"
FT   VARIANT         2296
FT                   /note="L -> P (in strain: Isolate H77)"
FT   VARIANT         2341
FT                   /note="P -> S (in strain: Isolate H77)"
FT   VARIANT         2355
FT                   /note="S -> P (in strain: Isolate H77)"
FT   VARIANT         2400
FT                   /note="L -> F (in strain: Isolate H77)"
FT   VARIANT         2425
FT                   /note="S -> T (in strain: Isolate H77)"
FT   VARIANT         2469
FT                   /note="K -> Q (in strain: Isolate H77)"
FT   VARIANT         2512
FT                   /note="A -> T (in strain: Isolate H77)"
FT   VARIANT         2637
FT                   /note="L -> F (in strain: Isolate H77)"
FT   VARIANT         2703
FT                   /note="R -> G (in strain: Isolate H77)"
FT   VARIANT         2715
FT                   /note="R -> C (in strain: Isolate H77)"
FT   VARIANT         2755
FT                   /note="S -> N (in strain: Isolate H77)"
FT   VARIANT         2925
FT                   /note="W -> R (in strain: Isolate H77)"
FT   VARIANT         2933
FT                   /note="A -> S (in strain: Isolate H77)"
FT   VARIANT         2937
FT                   /note="K -> R (in strain: Isolate H77)"
FT   VARIANT         2960
FT                   /note="T -> A (in strain: Isolate H77)"
FT   MUTAGEN         399
FT                   /note="L->R: Complete loss of E2 binding to host SCARB1;
FT                   5-10-fold decrease of infectivity for the viral particles."
FT                   /evidence="ECO:0000269|PubMed:22767607"
FT   MUTAGEN         429
FT                   /note="C->A: Complete loss of infectivity."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         452
FT                   /note="C->A: Complete loss of infectivity. Loss of
FT                   heterodimerization with E1. No effect on CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         459
FT                   /note="C->A: Complete loss of infectivity. Loss of
FT                   heterodimerization with E1. 78% loss of CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         486
FT                   /note="C->A: Complete loss of infectivity. No effect on
FT                   CD81-binding function. Loss of heterodimerization with E1."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         494
FT                   /note="C->A: Complete loss of infectivity and CD81-binding
FT                   function. Loss of heterodimerization with E1."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         503
FT                   /note="C->A: Complete loss of infectivity and CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         508
FT                   /note="C->A: Complete loss of infectivity and CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         552
FT                   /note="C->A: Complete loss of infectivity."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         564
FT                   /note="C->A: Complete loss of infectivity and CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         569
FT                   /note="C->A: Complete loss of infectivity. No effect on
FT                   CD81-binding function. Loss of heterodimerization with E1."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         581
FT                   /note="C->A: Complete loss of infectivity. No effect on
FT                   CD81-binding function. Loss of heterodimerization with E1."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         585
FT                   /note="C->A: Complete loss of infectivity. No effect on
FT                   CD81-binding function. Loss of heterodimerization with E1."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         597
FT                   /note="C->A: Complete loss of infectivity. Reduced
FT                   CD81-binding function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         607
FT                   /note="C->A: Complete loss of infectivity. Complete loss of
FT                   E2 expression probably due to the disruption of the global
FT                   conformation of the protein."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         620
FT                   /note="C->A: Complete loss of infectivity. Reduced
FT                   CD81-binding function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         644
FT                   /note="C->A: Complete loss of infectivity. Complete loss of
FT                   E2 expression probably due to the disruption of the global
FT                   conformation of the protein."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         652
FT                   /note="C->A: Complete loss of infectivity. Reduced
FT                   heterodimerization with E1. No effect on CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         677
FT                   /note="C->A: Complete loss of infectivity. Reduced
FT                   heterodimerization with E1. No effect on CD81-binding
FT                   function."
FT                   /evidence="ECO:0000269|PubMed:22278231"
FT   MUTAGEN         720
FT                   /note="V->L: Increases processing between E2 and p7."
FT                   /evidence="ECO:0000269|PubMed:15722527"
FT   MUTAGEN         779
FT                   /note="K->I: Virus can no longer infect chimpanzee."
FT                   /evidence="ECO:0000269|PubMed:14504405"
FT   MUTAGEN         781
FT                   /note="R->S: Virus can no longer infect chimpanzee."
FT                   /evidence="ECO:0000269|PubMed:14504405"
FT   MUTAGEN         922
FT                   /note="C->S: Complete loss of palmitoylation of NS2."
FT                   /evidence="ECO:0000269|PubMed:31597774"
FT   MUTAGEN         952
FT                   /note="H->A: Complete loss of NS2-NS3 cleavage."
FT                   /evidence="ECO:0000269|PubMed:16862121,
FT                   ECO:0000269|PubMed:8248148"
FT   MUTAGEN         993
FT                   /note="C->A: Complete loss of NS2-NS3 cleavage."
FT                   /evidence="ECO:0000269|PubMed:16862121,
FT                   ECO:0000269|PubMed:8248148"
FT   MUTAGEN         1083
FT                   /note="H->A: Complete loss of NS3-NS4A, NS4A-NS4B,
FT                   NS4B-NS5A and NS5A-NS5B cleavages."
FT                   /evidence="ECO:0000269|PubMed:8386278"
FT   MUTAGEN         1165
FT                   /note="S->A: Complete loss of NS3-NS4A, NS4A-NS4B,
FT                   NS4B-NS5A and NS5A-NS5B cleavages."
FT                   /evidence="ECO:0000269|PubMed:8248148,
FT                   ECO:0000269|PubMed:8386278"
FT   MUTAGEN         1968
FT                   /note="C->A: Strong decrease in NS4B palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:16731940"
FT   MUTAGEN         1972
FT                   /note="C->A: Slight decrease in NS4B palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:16731940"
FT   MUTAGEN         2321
FT                   /note="S->A: Loss of phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:10488152"
FT   STRAND          10..12
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   STRAND          16..18
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   TURN            19..23
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   STRAND          30..35
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   TURN            36..38
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   STRAND          39..41
FT                   /evidence="ECO:0007829|PDB:1CWX"
FT   HELIX           316..323
FT                   /evidence="ECO:0007829|PDB:4N0Y"
FT   STRAND          412..414
FT                   /evidence="ECO:0007829|PDB:5EOC"
FT   STRAND          416..418
FT                   /evidence="ECO:0007829|PDB:6BZY"
FT   STRAND          419..421
FT                   /evidence="ECO:0007829|PDB:6BZW"
FT   HELIX           422..424
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          425..427
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   TURN            432..435
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   HELIX           437..441
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          496..498
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   HELIX           499..501
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          502..516
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          532..534
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   STRAND          536..538
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   TURN            544..546
FT                   /evidence="ECO:0007829|PDB:6WO5"
FT   STRAND          551..556
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          561..564
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   HELIX           568..571
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   TURN            574..577
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   STRAND          579..581
FT                   /evidence="ECO:0007829|PDB:4MWF"
FT   STRAND          602..609
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   HELIX           614..617
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   HELIX           619..621
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          625..633
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   STRAND          636..644
FT                   /evidence="ECO:0007829|PDB:6UYD"
FT   HELIX           911..923
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   TURN            924..927
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   HELIX           931..944
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   TURN            951..953
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   HELIX           956..958
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   HELIX           964..967
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   TURN            971..974
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   STRAND          975..977
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   STRAND          982..984
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   TURN            988..990
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   STRAND          1000..1008
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   STRAND          1010..1013
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   TURN            1016..1018
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   HELIX           1019..1021
FT                   /evidence="ECO:0007829|PDB:2HD0"
FT   STRAND          1027..1030
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1032..1035
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   HELIX           1039..1048
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1057..1063
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1068..1074
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1077..1080
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   HELIX           1082..1085
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1090..1092
FT                   /evidence="ECO:0007829|PDB:2OC0"
FT   STRAND          1095..1097
FT                   /evidence="ECO:0007829|PDB:2OC0"
FT   STRAND          1100..1103
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   TURN            1104..1107
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1108..1112
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1129..1133
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1139..1144
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1146..1157
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   HELIX           1158..1160
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   TURN            1161..1163
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1168..1170
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   TURN            1172..1174
FT                   /evidence="ECO:0007829|PDB:2F9V"
FT   STRAND          1176..1186
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1189..1197
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   HELIX           1198..1205
FT                   /evidence="ECO:0007829|PDB:3RC4"
FT   STRAND          1224..1226
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   TURN            1236..1238
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1239..1246
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1251..1256
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1258..1271
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1277..1280
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1283..1285
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1290..1295
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1296..1301
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1304..1307
FT                   /evidence="ECO:0007829|PDB:1A1V"
FT   STRAND          1311..1316
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   TURN            1317..1319
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1323..1335
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   TURN            1336..1340
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1342..1347
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1362..1366
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1371..1375
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1378..1380
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1382..1385
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1386..1393
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1397..1409
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1414..1417
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1423..1425
FT                   /evidence="ECO:0007829|PDB:1A1V"
FT   STRAND          1428..1436
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1442..1444
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1449..1453
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1456..1463
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1467..1469
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1471..1478
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1481..1488
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1493..1495
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1497..1502
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1514..1527
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1532..1544
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1545..1548
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1555..1564
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1570..1578
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1584..1597
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1606..1611
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   TURN            1614..1618
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1627..1629
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1635..1637
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   HELIX           1640..1652
FT                   /evidence="ECO:0007829|PDB:1HEI"
FT   STRAND          1680..1687
FT                   /evidence="ECO:0007829|PDB:2O8M"
FT   HELIX           1753..1777
FT                   /evidence="ECO:0007829|PDB:2JXF"
FT   HELIX           1940..1964
FT                   /evidence="ECO:0007829|PDB:2KDR"
FT   HELIX           1976..1999
FT                   /evidence="ECO:0007829|PDB:1R7C"
FT   STRAND          2422..2426
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2445..2450
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2454..2456
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2457..2459
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2462..2464
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2465..2472
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2482..2495
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2505..2510
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2525..2529
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2533..2548
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2550..2552
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2556..2560
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2564..2566
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2569..2571
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2579..2582
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2585..2607
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2608..2610
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2612..2614
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2617..2629
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2631..2639
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2644..2647
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2650..2660
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2667..2679
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   TURN            2680..2682
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2684..2687
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2693..2697
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2707..2726
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2729..2736
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2739..2745
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2749..2765
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2770..2772
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2780..2782
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2788..2794
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2800..2806
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2809..2820
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2827..2835
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2839..2843
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2845..2855
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2863..2867
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2870..2874
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2876..2878
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2879..2887
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2889..2892
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2899..2912
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2917..2934
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2936..2945
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2947..2949
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2950..2952
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   HELIX           2960..2964
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   TURN            2968..2971
FT                   /evidence="ECO:0007829|PDB:2XI3"
FT   STRAND          2984..2986
FT                   /evidence="ECO:0007829|PDB:2N1P"
FT   HELIX           2994..3007
FT                   /evidence="ECO:0007829|PDB:2N1P"
SQ   SEQUENCE   3011 AA;  327146 MW;  772CBB29CCD94753 CRC64;
     MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG
     RRQPIPKARR PEGRTWAQPG YPWPLYGNEG CGWAGWLLSP RGSRPSWGPT DPRRRSRNLG
     KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA
     LLSCLTVPAS AYQVRNSSGL YHVTNDCPNS SVVYEAADAI LHTPGCVPCV REGNASRCWV
     AVTPTVATRD GKLPTTQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRHHWT
     TQDCNCSIYP GHITGHRMAW NMMMNWSPTA ALVVAQLLRI PQAIMDMIAG AHWGVLAGIK
     YFSMVGNWAK VLVVLLLFAG VDAETHVTGG NAGRTTAGLV GLLTPGAKQN IQLINTNGSW
     HINSTALNCN ESLNTGWLAG LFYQHKFNSS GCPERLASCR RLTDFAQGWG PISYANGSGL
     DERPYCWHYP PRPCGIVPAK SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ANDTDVFVLN
     NTRPPLGNWF GCTWMNSTGF TKVCGAPPCV IGGVGNNTLL CPTDCFRKYP EATYSRCGSG
     PRITPRCMVD YPYRLWHYPC TINYTIFKVR MYVGGVEHRL EAACNWTRGE RCDLEDRDRS
     ELSPLLLSTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGVGSSIA SWAIKWEYVV
     LLFLLLADAR VCSCLWMMLL ISQAEAALEN LVILNAASLA GTHGLVSFLV FFCFAWYLKG
     RWVPGAVYAL YGMWPLLLLL LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS
     WCMWWLQYFL TRVEAQLHVW VPPLNVRGGR DAVILLTCVV HPALVFDITK LLLAIFGPLW
     ILQASLLKVP YFVRVQGLLR ICALARKIAG GHYVQMAIIK LGALTGTCVY NHLAPLRDWA
     HNGLRDLAVA VEPVVFSRME TKLITWGADT AACGDIINGL PVSARRGQEI LLGPADGMVS
     KGWRLLAPIT AYAQQTRGLL GCIITSLTGR DKNQVEGEVQ IVSTATQTFL ATCINGVCWT
     VYHGAGTRTI ASPKGPVIQT YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI
     PVRRRGDSRG SLLSPRPISY LKGSSGGPLL CPTGHAVGLF RAAVCTRGVA KAVDFIPVEN
     LETTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAKGYK VLVLNPSVAA
     TLGFGAYMSK AHGVDPNIRT GVRTITTGSP ITYSTYGKFL ADAGCSGGAY DIIICDECHS
     TDATSISGIG TVLDQAETAG ARLVVLATAT PPGSVTVSHP NIEEVALSTT GEIPFYGKAI
     PLEVIKGGRH LIFCHSKKKC DELAAKLVAL GINAVAYYRG LDVSVIPTSG DVVVVSTDAL
     MTGFTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRTQRRGR TGRGKPGIYR
     FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV CQDHLGFWEG
     VFTGLTHIDA HFLSQTKQSG ENFPYLVAYQ ATVCARAQAP PPSWDQMRKC LIRLKPTLHG
     PTPLLYRLGA VQNEVTLTHP ITKYIMTCMS ADLEVVTSTW VLVGGVLAAL AAYCLSTGCV
     VIVGRIVLSG KPAIIPDREV LYQEFDEMEE CSQHLPYIEQ GMMLAEQFKQ KALGLLQTAS
     RHAEVITPAV QTNWQKLEVF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTAAVTSP
     LTTGQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAALD SVGLGKVLVD ILAGYGAGVA
     GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALAVGVVFAS ILRRRVGPGE GAVQWMNRLI
     AFASRGNHVS PTHYVPESDA AARVTAILSS LTVTQLLRRL HQWISSECTT PCSGSWLRDI
     WDWICEVLSD FKTWLKAKLM PQLPGIPFVS CQRGYRGVWR GDGIMHTRCH CGAEITGHVK
     NGTMRIVGPR TCKNMWSGTF FINAYTTGPC TPLPAPNYKF ALWRVSAEEY VEIRRVGDFH
     YVSGMTTDNL KCPCQIPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG LHEYPVGSQL
     PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSMAS SSASQLSAPS LKATCTANHD
     SPDAELIEAN LLWRQEMGGN ITRVESENKV VILDSFDPLV AEEDEREVSV PAEILRKSRR
     FAPALPVWAR PDYNPLLVET WKKPDYEPPV VHGCPLPPPR SPPVPPPRKK RTVVLTESTL
     PTALAELATK SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DVESYSSMPP LEGEPGDPDL
     SDGSWSTVSS GADTEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL LRHHNLVYST
     TSRSACQRKK KVTFDRLQVL DSHYQDVLKE VKAAASKVKA NLLSVEEACS LAPPHSAKSK
     FGYGAKDVRC HARKAVAHIN SVWKDLLEDS VTPIDTTIMA KNEVFCVQPE KGGRKPARLI
     VFPDLGVRVC EKMALYDVVS KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGLSYD
     TRCFDSTVTE SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR
     ASRVLTTSCG NTLTRYIKAR AACRAAGLQD CTMLVCGDDL VVICESAGVQ EDAASLRAFT
     EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR VYYLTRDPTT PLARAAWETA
     RHTPVNSWLG NIIMFAPTLW ARMILMTHFF SVLIARDQLE QALNCEIYGA CYSIEPLDLP
     PIIQRLHGLS AFSLHSYSPG EINRVAACLR KLGVPPLRAW RHRAWSVRAR LLARGGKAAI
     CGKYLFNWAV RTKLKLTPIT AAGRLDLSGW FTAGYSGGDI YHSVSHARPR WFWFCLLLLA
     AGVGIYLLPN R
//