POLG_HCV77
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 03-AUG-2022, entry version 233.
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; 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 (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 [92]
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 [93]
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 [94]
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 [95]
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 [96]
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 [97]
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 [98]
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 [99]
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 [100]
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 [101]
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 [102]
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 [103]
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 [104] {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 [105] {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 [106]
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 [107]
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 [108]
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 [109] {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 [110]
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 [111] {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 [112] {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 [113] {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 [114] {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 [115] {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 (By similarity). Both
CC hypo- and hyperphosphorylated states are required for the viral life
CC 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: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. {ECO:0000269|PubMed:20729191}.
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). {ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:11145889, ECO:0000269|PubMed:14990718,
CC ECO:0000269|PubMed:21147927, ECO:0000269|PubMed:24038151,
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 {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26663,
CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:10702287, ECO:0000269|PubMed:11801599,
CC ECO:0000269|PubMed:12021330, ECO:0000269|PubMed:12692242,
CC ECO:0000269|PubMed:12692249, ECO:0000269|PubMed:16530520,
CC ECO:0000269|PubMed:20926572, ECO:0000269|PubMed:22720086,
CC ECO:0000269|PubMed:23868571, ECO:0000269|PubMed:27194766,
CC ECO:0000269|PubMed:27282740, 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; 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; PRO_0000037569 [P27958]: -; NbExp=10; IntAct=EBI-6904269, EBI-6904259;
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_0000037572; PRO_0000037569 [P27958]: -; NbExp=2; IntAct=EBI-6919131, EBI-6904259;
CC PRO_0000037572; PRO_0000037571 [P27958]: -; NbExp=3; IntAct=EBI-6919131, EBI-6927261;
CC PRO_0000037572; PRO_0000037572 [P27958]: -; NbExp=2; IntAct=EBI-6919131, EBI-6919131;
CC PRO_0000037572; PRO_0000037574 [P27958]: -; NbExp=6; IntAct=EBI-6919131, EBI-6904374;
CC PRO_0000037572; PRO_0000037576 [P27958]: -; NbExp=4; IntAct=EBI-6919131, EBI-8753518;
CC PRO_0000037572; PRO_0000037577 [P27958]: -; NbExp=5; IntAct=EBI-6919131, EBI-6904388;
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_0000037572 [P27958]: -; NbExp=11; IntAct=EBI-3649474, EBI-6919131;
CC PRO_0000037573; PRO_0000037573 [P27958]: -; NbExp=3; IntAct=EBI-3649474, EBI-3649474;
CC PRO_0000037573; PRO_0000037575 [P27958]: -; NbExp=4; IntAct=EBI-3649474, EBI-8763498;
CC PRO_0000037573; PRO_0000037576 [P27958]: -; NbExp=8; IntAct=EBI-3649474, EBI-8753518;
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_0000037573 [P27958]: -; NbExp=17; IntAct=EBI-6904374, EBI-3649474;
CC PRO_0000037574; PRO_0000037576 [P27958]: -; NbExp=6; IntAct=EBI-6904374, EBI-8753518;
CC PRO_0000037574; PRO_0000037577 [P27958]: -; NbExp=8; IntAct=EBI-6904374, EBI-6904388;
CC PRO_0000037575; PRO_0000037572 [P27958]: -; NbExp=5; IntAct=EBI-8763498, EBI-6919131;
CC PRO_0000037575; PRO_0000037574 [P27958]: -; NbExp=4; IntAct=EBI-8763498, EBI-6904374;
CC PRO_0000037575; PRO_0000037575 [P27958]: -; NbExp=2; IntAct=EBI-8763498, EBI-8763498;
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_0000037575 [P27958]: -; NbExp=7; IntAct=EBI-8753518, EBI-8763498;
CC PRO_0000037576; PRO_0000037576 [P27958]: -; NbExp=2; IntAct=EBI-8753518, EBI-8753518;
CC PRO_0000037576; PRO_0000037577 [P27958]: -; NbExp=6; IntAct=EBI-8753518, EBI-6904388;
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_0000037575 [P27958]: -; NbExp=5; IntAct=EBI-6904388, EBI-8763498;
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 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 Ubiquitination, most probably at Lys-2350, mediated by host IFI27 and
CC SKP2 leads to proteasomal degradation, restricting viral infection
CC (PubMed:27194766). {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";
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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 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 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 PRIDE; 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; Genome.
DR Proteomes; UP000115192; Genome.
DR Proteomes; UP000180556; Genome.
DR GO; GO:0039714; C:cytoplasmic viral factory; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:AgBase.
DR GO; GO:0044164; C:host cell cytosol; IDA:AgBase.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IDA:AgBase.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044177; C:host cell Golgi apparatus; IDA:AgBase.
DR GO; GO:0044186; C:host cell lipid droplet; IDA:AgBase.
DR GO; GO:0033644; C:host cell membrane; IDA:AgBase.
DR GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:AgBase.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IDA:AgBase.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033647; C:host intracellular organelle; IMP:AgBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO: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; IMP:AgBase.
DR GO; GO:0060590; F:ATPase regulator activity; IDA:AgBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:AgBase.
DR GO; GO:0019899; F:enzyme binding; IPI:AgBase.
DR GO; GO:0031072; F:heat shock protein binding; IPI:AgBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:1990254; F:keratin filament binding; IPI:AgBase.
DR GO; GO:0019900; F:kinase binding; IDA:AgBase.
DR GO; GO:0042288; F:MHC class I protein binding; IPI:AgBase.
DR GO; GO:0140721; F:nuclease inhibitor activity; IMP:GO_Central.
DR GO; GO:0002039; F:p53 binding; IPI:AgBase.
DR GO; GO:0008233; F:peptidase activity; IDA:AgBase.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:AgBase.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IDA:AgBase.
DR GO; GO:0005124; F:scavenger receptor binding; IPI:AgBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:AgBase.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:AgBase.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IPI:AgBase.
DR GO; GO:0097677; F:STAT family protein binding; IPI:AgBase.
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:0008134; F:transcription factor binding; IPI:AgBase.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:AgBase.
DR GO; GO:0008270; F:zinc ion binding; IDA:AgBase.
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: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:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0044833; P:modulation by virus of host protein transport; IMP:AgBase.
DR GO; GO:0019056; P:modulation by virus of host transcription; IMP:AgBase.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IMP:AgBase.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IDA:AgBase.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:AgBase.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:AgBase.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; TAS:AgBase.
DR GO; GO:1900102; P:negative regulation of endoplasmic reticulum unfolded protein response; IDA:AgBase.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IMP:AgBase.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:AgBase.
DR GO; GO:0070104; P:negative regulation of interleukin-6-mediated signaling pathway; IMP:AgBase.
DR GO; GO:0033673; P:negative regulation of kinase activity; IMP:AgBase.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:AgBase.
DR GO; GO:0050709; P:negative regulation of protein secretion; IDA:AgBase.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:AgBase.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IDA:AgBase.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:AgBase.
DR GO; GO:0034156; P:negative regulation of toll-like receptor 7 signaling pathway; IDA:AgBase.
DR GO; GO:0034164; P:negative regulation of toll-like receptor 9 signaling pathway; IDA:AgBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:AgBase.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:AgBase.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:AgBase.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:1990216; P:positive regulation by symbiont of host transcription; IDA:AgBase.
DR GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; IDA:AgBase.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:AgBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:AgBase.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:AgBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:AgBase.
DR GO; GO:1903301; P:positive regulation of hexokinase activity; IDA:CACAO.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IDA:AgBase.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:AgBase.
DR GO; GO:0051047; P:positive regulation of secretion; IDA:AgBase.
DR GO; GO:0045727; P:positive regulation of translation; IMP:AgBase.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IDA:AgBase.
DR GO; GO:0048524; P:positive regulation of viral process; IDA:AgBase.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:1900101; P:regulation of endoplasmic reticulum unfolded protein response; IDA:AgBase.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IDA:AgBase.
DR GO; GO:0046774; P:suppression by virus of host intracellular interferon activity; IMP:AgBase.
DR GO; GO:0039560; P:suppression by virus of host JAK-STAT cascade via inhibition of host IRF9 activity; IMP:AgBase.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IDA:AgBase.
DR GO; GO:0039613; P:suppression by virus of host protein phosphorylation; IMP:AgBase.
DR GO; GO:0039547; P:suppression by virus of host TRAF activity; IDA:AgBase.
DR GO; GO:0039653; P:suppression by virus of host transcription; IDA:AgBase.
DR GO; GO:0039611; P:suppression by virus of host translation initiation factor activity; IDA:GO_Central.
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:0140533; P:suppression of host RNAi-mediated antiviral immune response; IDA:GO_Central.
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:0046762; P:viral budding from endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0019082; P:viral protein processing; TAS:AgBase.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR DisProt; DP00588; -.
DR Gene3D; 1.20.1280.150; -; 1.
DR Gene3D; 2.20.25.210; -; 1.
DR Gene3D; 2.20.25.220; -; 1.
DR Gene3D; 2.30.30.710; -; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 3.30.70.270; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR Gene3D; 4.10.710.10; -; 1.
DR InterPro; IPR011492; DEAD_Flavivir.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
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; NS3_Peptidase_S29.
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; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF56672; SSF56672; 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; 5-
FT 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 CD81-
FT 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 CD81-
FT 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, NS4B-
FT 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, NS4B-
FT 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
