POLG_HCVJA
ID POLG_HCVJA Reviewed; 3010 AA.
AC P26662; P89966; Q81755;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 207.
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:9060645};
DE EC=3.6.1.15 {ECO:0000269|PubMed:20398661};
DE EC=3.6.4.13 {ECO:0000269|PubMed:20398661};
DE AltName: Full=Hepacivirin;
DE AltName: Full=NS3 helicase {ECO:0000250|UniProtKB:P27958};
DE AltName: Full=NS3 protease {ECO:0000250|UniProtKB:P27958};
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:11907226};
DE AltName: Full=NS5B;
DE AltName: Full=p68;
OS Hepatitis C virus genotype 1b (isolate Japanese) (HCV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Hepacivirus.
OX NCBI_TaxID=11116;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2175903; DOI=10.1073/pnas.87.24.9524;
RA Kato N., Hijikata M., Ootsuyama Y., Nakagawa M., Ohkoshi S., Sugimura T.,
RA Shimotohno K.;
RT "Molecular cloning of the human hepatitis C virus genome from Japanese
RT patients with non-A, non-B hepatitis.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9524-9528(1990).
RN [2]
RP DISCUSSION OF SEQUENCE.
RX PubMed=1849488; DOI=10.1016/0014-5793(91)80322-t;
RA Kato N., Hijikata M., Nakagawa M., Ootsuyama Y., Muraiso K., Ohkoshi S.,
RA Shimotohno K.;
RT "Molecular structure of the Japanese hepatitis C viral genome.";
RL FEBS Lett. 280:325-328(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Tanaka T.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 723-1908, IDENTIFICATION (PROTEASE
RP NS2), MUTAGENESIS OF CYS-922; HIS-932; HIS-952; GLU-972; GLU-980; CYS-993;
RP GLU-1009; GLU-1058; HIS-1083; ASP-1107; CYS-1123; CYS-1125; HIS-1136;
RP SER-1165; CYS-1171; HIS-1175; CYS-1185; GLU-1199; GLU-1202; HIS-1227 AND
RP HIS-1229, IDENTIFICATION (SERINE PROTEASE/HELICASE NS3), AND ACTIVE SITE
RP (SERINE PROTEASE/HELICASE NS3).
RX PubMed=8392606; DOI=10.1128/jvi.67.8.4665-4675.1993;
RA Hijikata M., Mizushima H., Akagi T., Mori S., Kakiuchi N., Kato N.,
RA Tanaka T., Kimura K., Shimotohno K.;
RT "Two distinct proteinase activities required for the processing of a
RT putative nonstructural precursor protein of hepatitis C virus.";
RL J. Virol. 67:4665-4675(1993).
RN [5]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN).
RX PubMed=1648221; DOI=10.1073/pnas.88.13.5547;
RA Hijikata M., Kato N., Ootsuyama Y., Nakagawa M., Shimotohno K.;
RT "Gene mapping of the putative structural region of the hepatitis C virus
RT genome by in vitro processing analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5547-5551(1991).
RN [6]
RP INHIBITION OF HEPATITIS B VIRUS GENE EXPRESSION.
RX PubMed=8396658; DOI=10.1128/jvi.67.10.5823-5832.1993;
RA Shih C.-M., Lo S.J., Miyamura T., Chen S.-Y., Lee Y.-H.W.;
RT "Suppression of hepatitis B virus expression and replication by hepatitis C
RT virus core protein in HuH-7 cells.";
RL J. Virol. 67:5823-5832(1993).
RN [7]
RP PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN), MUTAGENESIS OF HIS-1083;
RP ASP-1107 AND SER-1165, IDENTIFICATION (SERINE PROTEASE/HELICASE NS3), AND
RP ACTIVE SITE (SERINE PROTEASE/HELICASE NS3).
RX PubMed=8389908; DOI=10.1128/jvi.67.7.3835-3844.1993;
RA Bartenschlager R., Ahlborn-Laake L., Mous J., Jacobsen H.;
RT "Nonstructural protein 3 of the hepatitis C virus encodes a serine-type
RT proteinase required for cleavage at the NS3/4 and NS4/5 junctions.";
RL J. Virol. 67:3835-3844(1993).
RN [8]
RP PHOSPHORYLATION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=7999043; DOI=10.1006/bbrc.1994.2667;
RA Kaneko T., Tanji Y., Satoh S., Hijikata M., Asabe S., Kimura K.,
RA Shimotohno K.;
RT "Production of two phosphoproteins from the NS5A region of the hepatitis C
RT viral genome.";
RL Biochem. Biophys. Res. Commun. 205:320-326(1994).
RN [9]
RP MUTAGENESIS OF SER-2194; SER-2197; SER-2200; SER-2201; SER-2202; SER-2204;
RP SER-2207; SER-2210 AND SER-2221, PHOSPHORYLATION AT SER-2194; SER-2197;
RP SER-2201 AND SER-2204, PHOSPHORYLATION (NON-STRUCTURAL PROTEIN 5A), AND
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=7769656; DOI=10.1128/jvi.69.7.3980-3986.1995;
RA Tanji Y., Kaneko T., Satoh S., Shimotohno K.;
RT "Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A.";
RL J. Virol. 69:3980-3986(1995).
RN [10]
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 4A (NON-STRUCTURAL PROTEIN 5A), AND
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 5A (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=8985418; DOI=10.1128/jvi.71.1.790-796.1997;
RA Asabe S.I., Tanji Y., Satoh S., Kaneko T., Kimura K., Shimotohno K.;
RT "The N-terminal region of hepatitis C virus-encoded NS5A is important for
RT NS4A-dependent phosphorylation.";
RL J. Virol. 71:790-796(1997).
RN [11]
RP FUNCTION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=9343247; DOI=10.1128/jvi.71.11.8856-8859.1997;
RA Kato N., Lan K.H., Ono-Nita S.K., Shiratori Y., Omata M.;
RT "Hepatitis C virus nonstructural region 5A protein is a potent
RT transcriptional activator.";
RL J. Virol. 71:8856-8859(1997).
RN [12]
RP ZINC-BINDING (SERINE PROTEASE/HELICASE NS3), COFACTOR (SERINE
RP PROTEASE/HELICASE NS3), MUTAGENESIS OF CYS-1042; CYS-1073; CYS-1078;
RP HIS-1083; HIS-1136; SER-1165; HIS-1175; CYS-1185; HIS-1227 AND HIS-1229,
RP ACTIVE SITE (SERINE PROTEASE/HELICASE NS3), DOMAIN (SERINE
RP PROTEASE/HELICASE NS3), AND CATALYTIC ACTIVITY (SERINE PROTEASE/HELICASE
RP NS3).
RX PubMed=9060645; DOI=10.1128/jvi.71.4.2881-2886.1997;
RA Stempniak M., Hostomska Z., Nodes B.R., Hostomsky Z.;
RT "The NS3 proteinase domain of hepatitis C virus is a zinc-containing
RT enzyme.";
RL J. Virol. 71:2881-2886(1997).
RN [13]
RP SUBCELLULAR LOCATION (MATURE CORE PROTEIN), AND PROTEOLYTIC CLEAVAGE
RP (GENOME POLYPROTEIN).
RX PubMed=9621068; DOI=10.1128/jvi.72.7.6048-6055.1998;
RA Yasui K., Wakita T., Tsukiyama-Kohara K., Funahashi S., Ichikawa M.,
RA Kajita T., Moradpour D., Wands J.R., Kohara M.;
RT "The native form and maturation process of hepatitis C virus core
RT protein.";
RL J. Virol. 72:6048-6055(1998).
RN [14]
RP DOMAIN (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=9525599; DOI=10.1128/jvi.72.4.2795-2805.1998;
RA Pawlotsky J.-M., Germanidis G., Neumann A.U., Pellerin M., Frainais P.-O.,
RA Dhumeaux D.;
RT "Interferon resistance of hepatitis C virus genotype 1b: relationship to
RT nonstructural 5A gene quasispecies mutations.";
RL J. Virol. 72:2795-2805(1998).
RN [15]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 5A), NUCLEAR LOCALIZATION
RP REGION (NON-STRUCTURAL PROTEIN 5A), AND PROTEOLYTIC CLEAVAGE
RP (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=10793006; DOI=10.1006/viro.2000.0287;
RA Satoh S., Hirota M., Noguchi T., Hijikata M., Handa H., Shimotohno K.;
RT "Cleavage of hepatitis C virus nonstructural protein 5A by a caspase-like
RT protease(s) in mammalian cells.";
RL Virology 270:476-487(2000).
RN [16]
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 [17]
RP OLIGOMERIZATION (RNA-DIRECTED RNA POLYMERASE), AND CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE).
RX PubMed=11907226; DOI=10.1128/jvi.76.8.3865-3872.2002;
RA Wang Q.M., Hockman M.A., Staschke K., Johnson R.B., Case K.A., Lu J.,
RA Parsons S., Zhang F., Rathnachalam R., Kirkegaard K., Colacino J.M.;
RT "Oligomerization and cooperative RNA synthesis activity of hepatitis C
RT virus RNA-dependent RNA polymerase.";
RL J. Virol. 76:3865-3872(2002).
RN [18]
RP INTERACTION WITH HOST SP110 (MATURE CORE PROTEIN), AND FUNCTION (MATURE
RP CORE PROTEIN).
RX PubMed=14559998; DOI=10.1128/mcb.23.21.7498-7509.2003;
RA Watashi K., Hijikata M., Tagawa A., Doi T., Marusawa H., Shimotohno K.;
RT "Modulation of retinoid signaling by a cytoplasmic viral protein via
RT sequestration of Sp110b, a potent transcriptional corepressor of retinoic
RT acid receptor, from the nucleus.";
RL Mol. Cell. Biol. 23:7498-7509(2003).
RN [19]
RP MUTAGENESIS OF LEU-139; VAL-140; LEU-144; 176-ILE-PHE-177; 178-LEU-LEU-179;
RP 181-LEU-LEU-182 AND 183-SER-CYS-184, PROTEOLYTIC CLEAVAGE (GENOME
RP POLYPROTEIN), SUBCELLULAR LOCATION (MATURE CORE PROTEIN), AND SUBCELLULAR
RP LOCATION (CORE PROTEIN PRECURSOR).
RX PubMed=15163730; DOI=10.1128/jvi.78.12.6370-6380.2004;
RA Okamoto K., Moriishi K., Miyamura T., Matsuura Y.;
RT "Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis
RT C virus core protein.";
RL J. Virol. 78:6370-6380(2004).
RN [20]
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 [21]
RP FUNCTION (MATURE CORE PROTEIN).
RX PubMed=15760888; DOI=10.1074/jbc.m501826200;
RA Boni S., Lavergne J.-P., Boulant S., Cahour A.;
RT "Hepatitis C virus core protein acts as a trans-modulating factor on
RT internal translation initiation of the viral RNA.";
RL J. Biol. Chem. 280:17737-17748(2005).
RN [22]
RP INTERACTION WITH HOST STAT1 (MATURE CORE PROTEIN), AND FUNCTION (MATURE
RP CORE PROTEIN).
RX PubMed=15825084; DOI=10.1053/j.gastro.2005.02.006;
RA Lin W., Choe W.H., Hiasa Y., Kamegaya Y., Blackard J.T., Schmidt E.V.,
RA Chung R.T.;
RT "Hepatitis C virus expression suppresses interferon signaling by degrading
RT STAT1.";
RL Gastroenterology 128:1034-1041(2005).
RN [23]
RP SUBCELLULAR LOCATION (MATURE CORE PROTEIN).
RX PubMed=15613354; DOI=10.1128/jvi.79.2.1271-1281.2005;
RA Suzuki R., Sakamoto S., Tsutsumi T., Rikimaru A., Tanaka K., Shimoike T.,
RA Moriishi K., Iwasaki T., Mizumoto K., Matsuura Y., Miyamura T., Suzuki T.;
RT "Molecular determinants for subcellular localization of hepatitis C virus
RT core protein.";
RL J. Virol. 79:1271-1281(2005).
RN [24]
RP FUNCTION (NON-STRUCTURAL PROTEIN 5A), AND RNA-BINDING (NON-STRUCTURAL
RP PROTEIN 5A).
RX PubMed=16126720; DOI=10.1074/jbc.m508175200;
RA Huang L., Hwang J., Sharma S.D., Hargittai M.R., Chen Y., Arnold J.J.,
RA Raney K.D., Cameron C.E.;
RT "Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding
RT protein.";
RL J. Biol. Chem. 280:36417-36428(2005).
RN [25]
RP INTERACTION WITH HOST VAPB (NON-STRUCTURAL PROTEIN 5A), INTERACTION WITH
RP HOST VAPB (RNA-DIRECTED RNA POLYMERASE), AND SUBCELLULAR LOCATION
RP (NON-STRUCTURAL PROTEIN 5A).
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 [26]
RP PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=16517592; DOI=10.1074/jbc.m601124200;
RA Kalamvoki M., Georgopoulou U., Mavromara P.;
RT "The NS5A protein of the hepatitis C virus genotype 1a is cleaved by
RT caspases to produce C-terminal-truncated forms of the protein that reside
RT mainly in the cytosol.";
RL J. Biol. Chem. 281:13449-13462(2006).
RN [27]
RP INTERACTION WITH HOST STAT1 (MATURE CORE PROTEIN), AND FUNCTION (MATURE
RP CORE PROTEIN).
RX PubMed=16940534; DOI=10.1128/jvi.00459-06;
RA Lin W., Kim S.S., Yeung E., Kamegaya Y., Blackard J.T., Kim K.A.,
RA Holtzman M.J., Chung R.T.;
RT "Hepatitis C virus core protein blocks interferon signaling by interaction
RT with the STAT1 SH2 domain.";
RL J. Virol. 80:9226-9235(2006).
RN [28]
RP INTERACTION WITH HOST FKBP8 (NON-STRUCTURAL PROTEIN 5A), AND SUBCELLULAR
RP LOCATION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=16844119; DOI=10.1016/j.febslet.2006.07.002;
RA Wang J., Tong W., Zhang X., Chen L., Yi Z., Pan T., Hu Y., Xiang L.,
RA Yuan Z.;
RT "Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and
RT inhibits apoptosis in Huh7 hepatoma cells.";
RL FEBS Lett. 580:4392-4400(2006).
RN [29]
RP INTERACTION WITH HOST EIF2AK2 (MATURE CORE PROTEIN).
RX PubMed=17267064; DOI=10.1016/j.virusres.2006.12.010;
RA Yan X.B., Battaglia S., Boucreux D., Chen Z., Brechot C., Pavio N.;
RT "Mapping of the interacting domains of hepatitis C virus core protein and
RT the double-stranded RNA-activated protein kinase PKR.";
RL Virus Res. 125:79-87(2007).
RN [30]
RP INTERACTION WITH HOST EIF2AK2 (NON-STRUCTURAL PROTEIN 5A), AND DOMAIN
RP (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=17451199; DOI=10.3748/wjg.v13.i8.1195;
RA Veillon P., Payan C., Le Guillou-Guillemette H., Gaudy C., Lunel F.;
RT "Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b
RT during interferon or combined interferon-ribavirin therapy.";
RL World J. Gastroenterol. 13:1195-1203(2007).
RN [31]
RP FUNCTION (SERINE PROTEASE/HELICASE NS3), CATALYTIC ACTIVITY (SERINE
RP PROTEASE/HELICASE NS3), AND COFACTOR (SERINE PROTEASE/HELICASE NS3).
RX PubMed=20398661; DOI=10.1016/j.febslet.2010.04.020;
RA Huang Z.S., Wang C.C., Wu H.N.;
RT "HCV NS3 protein helicase domain assists RNA structure conversion.";
RL FEBS Lett. 584:2356-2362(2010).
RN [32]
RP GLYCOSYLATION AT THR-385; THR-396; SER-401; SER-404; THR-473 AND THR-518,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=HCV-S;
RX PubMed=23242014; DOI=10.1093/glycob/cws171;
RA Braeutigam J., Scheidig A.J., Egge-Jacobsen W.;
RT "Mass spectrometric analysis of hepatitis C viral envelope protein E2
RT reveals extended microheterogeneity of mucin-type O-linked glycosylation.";
RL Glycobiology 23:453-474(2013).
RN [33]
RP INTERACTION WITH HOST RAB18 (NON-STRUCTURAL PROTEIN 5A), AND SUBCELLULAR
RP LOCATION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=23935497; DOI=10.1371/journal.ppat.1003513;
RA Salloum S., Wang H., Ferguson C., Parton R.G., Tai A.W.;
RT "Rab18 binds to hepatitis C virus NS5A and promotes interaction between
RT sites of viral replication and lipid droplets.";
RL PLoS Pathog. 9:e1003513-e1003513(2013).
RN [34]
RP FUNCTION (NON-STRUCTURAL PROTEIN 5A), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP PROTEIN 5A), DOMAIN (NON-STRUCTURAL PROTEIN 5A), NUCLEAR LOCALIZATION
RP REGION (NON-STRUCTURAL PROTEIN 5A), AND MUTAGENESIS OF ASP-2126.
RX PubMed=23468497; DOI=10.1128/jvi.00585-12;
RA Maqbool M.A., Imache M.R., Higgs M.R., Carmouse S., Pawlotsky J.M.,
RA Lerat H.;
RT "Regulation of hepatitis C virus replication by nuclear translocation of
RT nonstructural 5A protein and transcriptional activation of host genes.";
RL J. Virol. 87:5523-5539(2013).
RN [35]
RP PHOSPHORYLATION AT SER-2448 AND SER-2461, PHOSPHORYLATION (RNA-DIRECTED RNA
RP POLYMERASE), AND MUTAGENESIS OF SER-2448 AND SER-2461.
RX PubMed=25031343; DOI=10.1128/jvi.01826-14;
RA Han S.H., Kim S.J., Kim E.J., Kim T.E., Moon J.S., Kim G.W., Lee S.H.,
RA Cho K., Yoo J.S., Son W.S., Rhee J.K., Han S.H., Oh J.W.;
RT "Phosphorylation of hepatitis C virus RNA polymerases ser29 and ser42 by
RT protein kinase C-related kinase 2 regulates viral RNA replication.";
RL J. Virol. 88:11240-11252(2014).
RN [36]
RP FUNCTION (NON-STRUCTURAL PROTEIN 5A), MUTAGENESIS OF SER-2194; SER-2197;
RP SER-2201; SER-2204; SER-2207 AND SER-2210, AND SUBUNIT (NON-STRUCTURAL
RP PROTEIN 5A).
RX PubMed=31585734; DOI=10.1016/j.bbrc.2019.09.105;
RA Kandangwa M., Liu Q.;
RT "HCV NS5A hyperphosphorylation is involved in viral translation
RT modulation.";
RL Biochem. Biophys. Res. Commun. 520:192-197(2019).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1027-1213.
RX PubMed=10702283; DOI=10.1074/jbc.275.10.7152;
RA Di Marco S., Rizzi M., Volpari C., Walsh M.A., Narjes F., Colarusso S.,
RA De Francesco R., Matassa V.G., Sollazzo M.;
RT "Inhibition of the hepatitis C virus NS3/4A protease. The crystal
RT structures of two protease-inhibitor complexes.";
RL J. Biol. Chem. 275:7152-7157(2000).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1027-1213 IN COMPLEX WITH A
RP PEPTIDOMIMETIC INHIBITOR.
RX PubMed=15588076; DOI=10.1021/jm049435d;
RA Ontoria J.M., Di Marco S., Conte I., Di Francesco M.E., Gardelli C.,
RA Koch U., Matassa V.G., Poma M., Steinkuehler C., Volpari C., Harper S.;
RT "The design and enzyme-bound crystal structure of indoline based
RT peptidomimetic inhibitors of hepatitis C virus NS3 protease.";
RL J. Med. Chem. 47:6443-6446(2004).
RN [39] {ECO:0007744|PDB:2K8J}
RP STRUCTURE BY NMR OF 781-809, AND FUNCTION (VIROPORIN P7).
RX PubMed=20667830; DOI=10.1074/jbc.m110.122895;
RA Montserret R., Saint N., Vanbelle C., Salvay A.G., Simorre J.P., Ebel C.,
RA Sapay N., Renisio J.G., Bockmann A., Steinmann E., Pietschmann T.,
RA Dubuisson J., Chipot C., Penin F.;
RT "NMR structure and ion channel activity of the p7 protein from hepatitis C
RT virus.";
RL J. Biol. Chem. 285:31446-31461(2010).
RN [40] {ECO:0007744|PDB:3P8N, ECO:0007744|PDB:3P8O}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1027-1206 AND 1678-1691.
RX PubMed=21270126; DOI=10.1074/jbc.m110.211417;
RA Lemke C.T., Goudreau N., Zhao S., Hucke O., Thibeault D., Llinas-Brunet M.,
RA White P.W.;
RT "Combined X-ray, NMR, and kinetic analyses reveal uncommon binding
RT characteristics of the hepatitis C virus NS3-NS4A protease inhibitor BI
RT 201335.";
RL J. Biol. Chem. 286:11434-11443(2011).
RN [41] {ECO:0007744|PDB:3OYP}
RP X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) OF 1027-1213 AND 1678-1691 IN
RP COMPLEX WITH ZINC.
RX PubMed=21113170; DOI=10.1038/nchembio.492;
RA Hagel M., Niu D., St Martin T., Sheets M.P., Qiao L., Bernard H.,
RA Karp R.M., Zhu Z., Labenski M.T., Chaturvedi P., Nacht M., Westlin W.F.,
RA Petter R.C., Singh J.;
RT "Selective irreversible inhibition of a protease by targeting a
RT noncatalytic cysteine.";
RL Nat. Chem. Biol. 7:22-24(2011).
RN [42] {ECO:0007744|PDB:4A1T, ECO:0007744|PDB:4A1V, ECO:0007744|PDB:4A1X}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1028-1206 AND 1678-1690 IN
RP COMPLEX WITH ZINC.
RX PubMed=22965230; DOI=10.1074/jbc.m112.393843;
RA Kugler J., Schmelz S., Gentzsch J., Haid S., Pollmann E.,
RA van den Heuvel J., Franke R., Pietschmann T., Heinz D.W., Collins J.;
RT "High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease
RT refractory to common resistant mutants.";
RL J. Biol. Chem. 287:39224-39232(2012).
RN [43] {ECO:0007744|PDB:4I31, ECO:0007744|PDB:4I32, ECO:0007744|PDB:4I33}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1027-1206; 1208-1208 AND
RP 1678-1691.
RX PubMed=23271737; DOI=10.1074/jbc.m112.439455;
RA O'Meara J.A., Lemke C.T., Godbout C., Kukolj G., Lagace L., Moreau B.,
RA Thibeault D., White P.W., Llinas-Brunet M.;
RT "Molecular mechanism by which a potent hepatitis C virus NS3-NS4A protease
RT inhibitor overcomes emergence of resistance.";
RL J. Biol. Chem. 288:5673-5681(2013).
RN [44] {ECO:0007744|PDB:4JMY}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1678-1691.
RA LaPlante S., Lemke C.T.;
RT "Importance of the peptide scaffold of drugs that target the hepatitis C
RT virus NS3 protease and its crucial bioactive conformation and dynamic
RT factors.";
RL Submitted (MAR-2013) to the PDB data bank.
RN [45] {ECO:0007744|PDB:4KTC}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1028-1213 IN COMPLEX WITH ZINC.
RX PubMed=23672640; DOI=10.1021/jm400164c;
RA Jiang Y., Andrews S.W., Condroski K.R., Buckman B., Serebryany V.,
RA Wenglowsky S., Kennedy A.L., Madduru M.R., Wang B., Lyon M., Doherty G.A.,
RA Woodard B.T., Lemieux C., Geck Do M., Zhang H., Ballard J., Vigers G.,
RA Brandhuber B.J., Stengel P., Josey J.A., Beigelman L., Blatt L.,
RA Seiwert S.D.;
RT "Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent
RT inhibitor of hepatitis C virus (HCV) NS3/4A protease.";
RL J. Med. Chem. 57:1753-1769(2014).
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 (By similarity). Modulates viral
CC translation initiation by interacting with viral IRES and 40S ribosomal
CC subunit (PubMed:15760888). Affects various cell signaling pathways,
CC host immunity and lipid metabolism (Probable). Prevents the
CC establishment of cellular antiviral state by blocking the interferon-
CC alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by
CC blocking the formation of phosphorylated STAT1 and promoting ubiquitin-
CC mediated proteasome-dependent degradation of STAT1 (PubMed:16940534,
CC PubMed:15825084). Activates STAT3 leading to cellular transformation
CC (By similarity). Regulates the activity of cellular genes, including c-
CC myc and c-fos (By similarity). May repress the promoter of p53, and
CC sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm
CC (PubMed:14559998). Represses cell cycle negative regulating factor
CC CDKN1A, thereby interrupting an important check point of normal cell
CC cycle regulation (By similarity). Targets transcription factors
CC involved in the regulation of inflammatory responses and in the immune
CC response: suppresses NF-kappa-B activation, and activates AP-1 (By
CC similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in
CC down-regulation of T-lymphocytes proliferation (By similarity). Alters
CC lipid metabolism by interacting with hepatocellular proteins involved
CC in lipid accumulation and storage (By similarity). Induces up-
CC regulation of FAS promoter activity, and thereby contributes to the
CC increased triglyceride accumulation in hepatocytes (steatosis) (By
CC similarity). {ECO:0000250|UniProtKB:P26664,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:14559998,
CC ECO:0000269|PubMed:15760888, ECO:0000269|PubMed:15825084,
CC ECO:0000269|PubMed:16940534, 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 (By similarity). Fusion with the host cell is
CC most likely mediated by both E1 and E2, through conformational
CC rearrangements of the heterodimer required for fusion rather than a
CC classical class II fusion mechanism (By similarity). E1/E2 heterodimer
CC binds host apolipoproteins such as APOB and APOE thereby forming a
CC lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP
CC allows the initial virus attachment to cell surface receptors such as
CC the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-
CC 1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger
CC receptor class B type I (SCARB1) (By similarity). The cholesterol
CC transfer activity of SCARB1 allows E2 exposure and binding of E2 to
CC SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer
CC binding on CD81 activates the epithelial growth factor receptor (EGFR)
CC signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-
CC SCARB1-CD81 to the cell lateral membrane allows further interaction
CC with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry
CC (By similarity). {ECO:0000250|UniProtKB:P27958}.
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 (By similarity). Fusion with the host cell is
CC most likely mediated by both E1 and E2, through conformational
CC rearrangements of the heterodimer required for fusion rather than a
CC classical class II fusion mechanism (By similarity). The interaction
CC between envelope glycoprotein E2 and host apolipoprotein E/APOE allows
CC the proper assembly, maturation and infectivity of the viral particles
CC (By similarity). This interaction is probably promoted via the up-
CC regulation of cellular autophagy by the virus (By similarity). E1/E2
CC heterodimer binds host apolipoproteins such as APOB and APOE thereby
CC forming a lipo-viro-particle (LVP) (By similarity). APOE associated to
CC the LVP allows the initial virus attachment to cell surface receptors
CC such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1),
CC syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and
CC scavenger receptor class B type I (SCARB1) (By similarity). The
CC cholesterol transfer activity of SCARB1 allows E2 exposure and binding
CC of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2
CC heterodimer binding on CD81 activates the epithelial growth factor
CC receptor (EGFR) signaling pathway (By similarity). Diffusion of the
CC complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows
CC further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to
CC finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR
CC activation, preventing the establishment of an antiviral state (By
CC similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which
CC are respectively found on dendritic cells (DCs), and on liver
CC sinusoidal endothelial cells and macrophage-like cells of lymph node
CC sinuses (By similarity). 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 (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.
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:20667830). Regulates the host cell secretory
CC pathway, which induces the intracellular retention of viral
CC glycoproteins and favors assembly of viral particles (By similarity).
CC Creates 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 (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane
CC trafficking and transport of viral ER-associated proteins to
CC viroplasms, sites of viral genome replication (Probable). This ionic
CC imbalance induces the assembly of the inflammasome complex, which
CC triggers the maturation of pro-IL-1beta into IL-1beta through the
CC action of caspase-1 (By similarity). Targets also host mitochondria and
CC induces mitochondrial depolarization (By similarity). In addition of
CC its role as a viroporin, acts as a lipid raft adhesion factor (By
CC similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:20667830,
CC ECO:0000305}.
CC -!- FUNCTION: [Protease NS2]: Cysteine protease required for the
CC proteolytic auto-cleavage between the non-structural proteins NS2 and
CC NS3 (By similarity). The N-terminus of NS3 is required for the function
CC of NS2 protease (active region NS2-3) (By similarity). Promotes the
CC initiation of viral particle assembly by mediating the interaction
CC between structural and non-structural proteins (By similarity).
CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8}.
CC -!- FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic
CC activities: serine protease with a chymotrypsin-like fold, NTPase and
CC RNA helicase (By similarity). NS3 serine protease, in association with
CC NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-
CC NS5A and NS5A-NS5B (By similarity). 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 (By similarity). NS3 RNA helicase binds to RNA and
CC unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely
CC resolves RNA complicated stable secondary structures in the template
CC strand (By similarity). Binds a single ATP and catalyzes the unzipping
CC of a single base pair of dsRNA (By similarity). Inhibits host antiviral
CC proteins TBK1 and IRF3 thereby preventing the establishment of an
CC antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby
CC preventing the establishment of an antiviral state (By similarity).
CC Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and
CC preventing the establishment of an antiviral state (By similarity).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.
CC -!- FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a
CC non-covalent complex with the N-terminal of NS3 serine protease (By
CC similarity). 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 (By
CC similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q9WMX2}.
CC -!- FUNCTION: [Non-structural protein 4B]: Induces a specific membrane
CC alteration that serves as a scaffold for the virus replication complex
CC (By similarity). This membrane alteration gives rise to the so-called
CC ER-derived membranous web that contains the replication complex (By
CC similarity). NS4B self-interaction contributes to its function in
CC membranous web formation (By similarity). Promotes host TRIF protein
CC degradation in a CASP8-dependent manner thereby inhibiting host TLR3-
CC mediated interferon signaling (By similarity). Disrupts the interaction
CC between STING and TBK1 contributing to the inhibition of interferon
CC signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.
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 (PubMed:16126720). Zinc
CC is essential for RNA-binding (By similarity). Participates in the viral
CC particle production as a result of its interaction with the mature
CC viral core protein (By similarity). Its interaction with host VAPB may
CC target the viral replication complex to vesicles (Probable). Down-
CC regulates viral IRES translation initiation (PubMed:31585734). Mediates
CC interferon resistance, presumably by interacting with and inhibiting
CC host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By
CC similarity). Acts as a transcriptional activator of some host genes
CC important for viral replication when localized in the nucleus
CC (PubMed:23468497) (Probable). Via the interaction with host PACSIN2,
CC modulates lipid droplet formation in order to promote virion assembly
CC (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral
CC propagation (By similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2,
CC ECO:0000269|PubMed:16126720, ECO:0000269|PubMed:23468497,
CC ECO:0000269|PubMed:31585734, ECO:0000305|PubMed:16227268,
CC ECO:0000305|PubMed:9343247}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase
CC that performs primer-template recognition and RNA synthesis during
CC viral replication. {ECO:0000250|UniProtKB:P27958}.
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:9060645};
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:20398661};
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:20398661};
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:11907226};
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:0000269|PubMed:9060645};
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 (PubMed:9060645).
CC The magnesium ion is essential for the helicase activity
CC (PubMed:20398661). {ECO:0000269|PubMed:20398661,
CC ECO:0000269|PubMed:9060645};
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: Inhibited by the antiviral drug hexamethylene
CC amiloride (Probable). Inhibition by amantadine appears to be genotype-
CC dependent (Probable). Also inhibited by long-alkyl-chain iminosugar
CC derivatives (By similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000305|PubMed:20667830}.
CC -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Activity is up-
CC regulated by PRK2/PKN2-mediated phosphorylation.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- SUBUNIT: [Mature core protein]: Homooligomer (By similarity). Interacts
CC with E1 (via C-terminus) (By similarity). Interacts with the non-
CC structural protein 5A (By similarity). Interacts (via N-terminus) with
CC 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:16940534, PubMed:15825084). Interacts with host STAT3; this
CC interaction constitutively activates STAT3 (By similarity). Interacts
CC with host LTBR receptor (By similarity). Interacts with host TNFRSF1A
CC receptor and possibly induces apoptosis (By similarity). Interacts with
CC host 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 (PubMed:14559998). Interacts
CC with host CREB3 nuclear transcription protein; this interaction
CC triggers cell transformation (By similarity). Interacts with host ACY3
CC (By similarity). Interacts with host C1QR1 (By similarity). Interacts
CC with host RBM24; this interaction, which enhances the interaction of
CC the mature core protein with 5'-UTR, may inhibit viral translation and
CC favor replication (By similarity). Interacts with host EIF2AK2/PKR;
CC this interaction induces the autophosphorylation of EIF2AK2
CC (PubMed:17267064). 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:P27958,
CC ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q03463,
CC ECO:0000250|UniProtKB:Q5EG65, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:14559998, ECO:0000269|PubMed:15825084,
CC ECO:0000269|PubMed:16940534, ECO:0000269|PubMed:17267064}.
CC -!- SUBUNIT: [Envelope glycoprotein E1]: Forms a heterodimer with envelope
CC glycoprotein E2 (By similarity). Interacts with mature core protein (By
CC similarity). Interacts with protease NS2 (By similarity). The
CC heterodimer E1/E2 interacts with host CLDN1; this interaction plays a
CC role in viral entry into host cell (By similarity). Interacts with host
CC SPSB2 (via C-terminus) (By similarity). 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:P27958,
CC ECO:0000250|UniProtKB:Q99IB8}.
CC -!- SUBUNIT: [Envelope glycoprotein E2]: Forms a heterodimer with envelope
CC glycoprotein E1 (By similarity). Interacts with host CD81 and SCARB1
CC receptors; these interactions play a role in viral entry into host cell
CC (By similarity). Interacts with host EIF2AK2/PKR; this interaction
CC inhibits EIF2AK2 and probably allows the virus to evade the innate
CC immune response (By similarity). Interacts with host CD209/DC-SIGN and
CC CLEC4M/DC-SIGNR (By similarity). Interact with host SPCS1; this
CC interaction is essential for viral particle assembly (By similarity).
CC Interacts with protease NS2 (By similarity). The heterodimer E1/E2
CC interacts with host CLDN1; this interaction plays a role in viral entry
CC into host cell (By similarity). 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 (By similarity).
CC Interacts with human PLSCR1 (By similarity).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000250|UniProtKB:Q9WMX2}.
CC -!- SUBUNIT: [Viroporin p7]: Homohexamer (By similarity). Homoheptamer (By
CC similarity). Interacts with protease NS2 (By similarity).
CC {ECO:0000250|UniProtKB:O92972, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8}.
CC -!- SUBUNIT: [Protease NS2]: Homodimer (By similarity). Interacts with host
CC SPCS1; this interaction is essential for viral particle assembly (By
CC similarity). Interacts with envelope glycoprotein E1 (By similarity).
CC Interacts with envelope glycoprotein E2 (By similarity). Interacts with
CC viroporin p7 (By similarity). Interacts with serine protease/helicase
CC NS3 (By similarity). 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 (By similarity). 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:P27958, ECO:0000250|UniProtKB:Q99IB8}.
CC -!- SUBUNIT: [Serine protease/helicase NS3]: Interacts with protease NS2
CC (By similarity). 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 (By similarity). NS3/NS4A
CC complex also prevents phosphorylation of host IRF3, thus preventing the
CC establishment of dsRNA induced antiviral state (By similarity).
CC Interacts with host MAVS; this interaction leads to the cleavage and
CC inhibition of host MAVS (By similarity). Interacts with host TICAM1;
CC this interaction leads to the cleavage and inhibition of host TICAM1
CC (By similarity). 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 (By
CC similarity). Part of the viral assembly initiation complex composed of
CC NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By
CC similarity). {ECO:0000250|UniProtKB:P26663,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000250|UniProtKB:Q9WMX2}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with NS3 serine
CC protease; this interaction stabilizes the folding of NS3 serine
CC protease (By similarity). NS3-NS4A interaction is essential for NS3
CC activation and allows membrane anchorage of the latter (By similarity).
CC Interacts with non-structural protein 5A (via N-terminus)
CC (PubMed:8985418). Part of the replication complex composed of NS2, NS3,
CC NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-
CC derived membranous web (By similarity). 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:P26663,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:8985418}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Homomultimer (By similarity).
CC Interacts with non-structural protein NS5A (By similarity). 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 (By similarity). Part
CC of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and
CC the RNA-directed RNA polymerase embedded in an ER-derived membranous
CC web (By similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8}.
CC -!- SUBUNIT: [Non-structural protein 5A]: Monomer (By similarity).
CC Homodimer; dimerization is required for RNA-binding (Probable).
CC Interacts with the mature core protein (By similarity). Interacts (via
CC N-terminus) with non-structural protein 4A (PubMed:8985418). Interacts
CC with non-structural protein 4B (By similarity). Interacts with RNA-
CC directed RNA polymerase (By similarity). Part of the viral assembly
CC initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the
CC mature core protein (By similarity). Part of the replication complex
CC composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA
CC polymerase (By similarity). Interacts with host GRB2 (By similarity).
CC Interacts with host BIN1 (By similarity). Interacts with host PIK3R1
CC (By similarity). Interacts with host SRCAP (By similarity). Interacts
CC with host FKBP8 (PubMed:16844119). Interacts with host VAPB
CC (PubMed:16227268). Interacts with host EIF2AK2/PKR; this interaction
CC leads to disruption of EIF2AK2 dimerization by NS5A and probably allows
CC the virus to evade the innate immune response (PubMed:17451199).
CC Interacts (via N-terminus) with host PACSIN2 (via N-terminus); this
CC interaction attenuates protein kinase C alpha-mediated phosphorylation
CC of PACSIN2 by disrupting the interaction between PACSIN2 and PRKCA (By
CC similarity). Interacts (via N-terminus) with host SRC kinase (via SH2
CC 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 (By similarity).
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 (By
CC similarity). Interacts (via N-terminus) with host CIDEB (via N-
CC terminus); this interaction seems to regulate the association of HCV
CC particles with APOE (By similarity). 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 (By similarity). Interacts with
CC host RAB18; this interaction may promote the association of NS5A and
CC other replicase components with lipid droplets (PubMed:23935497).
CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P26664,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:16227268, ECO:0000269|PubMed:16844119,
CC ECO:0000269|PubMed:17451199, ECO:0000269|PubMed:23935497,
CC ECO:0000269|PubMed:8985418, ECO:0000305|PubMed:31585734}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Homooligomer (PubMed:11907226).
CC Interacts with non-structural protein 5A (By similarity). Interacts
CC with host VAPB (PubMed:16227268). Interacts with host PRK2/PKN2
CC (PubMed:25031343). Interacts with host HNRNPA1 and SEPT6; these
CC interactions facilitate the viral replication (By similarity). Part of
CC the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the
CC RNA-directed RNA polymerase (By similarity).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:11907226,
CC ECO:0000269|PubMed:16227268, ECO:0000269|PubMed:25031343}.
CC -!- INTERACTION:
CC PRO_0000037645; PRO_0000037644 [P26662]: -; NbExp=2; IntAct=EBI-8872853, EBI-8872843;
CC PRO_0000037647; Q07812: BAX; Xeno; NbExp=3; IntAct=EBI-9099462, EBI-516580;
CC PRO_0000037647; P62993: GRB2; Xeno; NbExp=3; IntAct=EBI-9099462, EBI-401755;
CC -!- SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:15163730,
CC ECO:0000269|PubMed:15613354, ECO:0000305|PubMed:9621068}; Single-pass
CC membrane protein {ECO:0000255}. Host mitochondrion membrane
CC {ECO:0000269|PubMed:15613354}; 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:9621068}. Host nucleus
CC {ECO:0000269|PubMed:15163730, ECO:0000269|PubMed:15613354,
CC ECO:0000269|PubMed:9621068}. Host lipid droplet
CC {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core
CC protein is present in the nucleus (By similarity). Probably present on
CC the surface of lipid droplets (By similarity).
CC {ECO:0000250|UniProtKB:P27958}.
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:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane
CC domain acts as a signal sequence and forms a hairpin structure before
CC cleavage by host signal peptidase (By similarity). After cleavage, the
CC membrane sequence is retained at the C-terminus of the protein, serving
CC as ER membrane anchor (By similarity). A reorientation of the second
CC hydrophobic stretch occurs after cleavage producing a single reoriented
CC transmembrane domain (By similarity). These events explain the final
CC topology of the protein (By similarity).
CC {ECO:0000250|UniProtKB:P27958}.
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:0000250|UniProtKB:P27958}. 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 (By similarity). After cleavage, the
CC membrane sequence is retained at the C-terminus of the protein, serving
CC as ER membrane anchor (By similarity). A reorientation of the second
CC hydrophobic stretch occurs after cleavage producing a single reoriented
CC transmembrane domain (By similarity). These events explain the final
CC topology of the protein (By similarity).
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:Q99IB8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q99IB8}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P27958}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q99IB8}. Note=The C-terminus of p7 membrane
CC domain acts as a signal sequence (By similarity). After cleavage by
CC host signal peptidase, the membrane sequence is retained at the C-
CC terminus of the protein, serving as ER membrane anchor (By similarity).
CC ER retention of p7 is leaky and a small fraction reaches the plasma
CC membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.
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:0000250|UniProtKB:P27958}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-
CC terminus into the ER lumen occurs post-translationally.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:16227268,
CC ECO:0000269|PubMed:16844119}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:7769656}. Host mitochondrion
CC {ECO:0000269|PubMed:16844119}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27958}. Host nucleus
CC {ECO:0000269|PubMed:23468497}. Host lipid droplet
CC {ECO:0000269|PubMed:23935497}. Note=Host membrane insertion occurs
CC after processing by the NS3 protease (By similarity). Localizes at the
CC surface of lipid droplets (PubMed:23935497).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:23935497}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm
CC {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane;
CC Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}.
CC Note=Host membrane insertion occurs after processing by the NS3
CC protease. {ECO:0000250|UniProtKB:P27958}.
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:0000250|UniProtKB:P27958}.
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 (By similarity).
CC Envelope E2 glycoprotein contain two highly variable regions called
CC hypervariable region 1 and 2 (HVR1 and HVR2) (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.
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 of
CC serine protease/helicase NS3 contains the protease activity
CC (PubMed:9060645). This region contains a zinc atom that does not belong
CC to the active site, but may play a structural rather than a catalytic
CC role (PubMed:9060645). This region is essential for the activity of
CC protease NS2, maybe by contributing to the folding of the latter
CC (PubMed:9060645). The NTPase/helicase activity is located in the
CC twothirds C-terminus of NS3, this domain contains the NTPase and RNA-
CC binding regions (By similarity). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000269|PubMed:9060645}.
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 of NS5A acts as
CC membrane anchor (By similarity). The central part of NS5A contains a
CC variable region called interferon sensitivity determining region (ISDR)
CC and seems to be intrinsically disordered and interacts with NS5B and
CC host EIF2AK2 (PubMed:9525599, PubMed:17451199). The C-terminus of NS5A
CC contains a variable region called variable region 3 (V3)
CC (PubMed:17451199). ISDR and V3 may be involved in sensitivity and/or
CC resistance to IFN-alpha therapy (PubMed:9525599, PubMed:17451199). The
CC C-terminus contains a nuclear localization signal (PubMed:23468497).
CC The SH3-binding domain is involved in the interaction with host BIN1,
CC GRB2 and Src-family kinases (By similarity).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:17451199,
CC ECO:0000269|PubMed:23468497, ECO:0000269|PubMed:9525599}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC mature proteins (By similarity). The structural proteins, core, E1, E2
CC and p7 are produced by proteolytic processing by host signal peptidases
CC (By similarity). The core protein is synthesized as a 23 kDa precursor
CC which is retained in the ER membrane through the hydrophobic signal
CC peptide (PubMed:9621068, PubMed:15163730). Cleavage by the signal
CC peptidase releases the 21 kDa mature core protein (PubMed:9621068,
CC PubMed:15163730). The cleavage of the core protein precursor occurs
CC between aminoacids 176 and 188 but the exact cleavage site is not known
CC (By similarity). Some degraded forms of the core protein appear as well
CC during the course of infection (By similarity). The other proteins (p7,
CC NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases
CC (PubMed:8389908). Autoprocessing between NS2 and NS3 is mediated by the
CC NS2 cysteine protease catalytic domain and regulated by the NS3 N-
CC terminal domain (By similarity). {ECO:0000250|UniProtKB:P26663,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:15163730, ECO:0000269|PubMed:8389908,
CC ECO:0000269|PubMed:9621068}.
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:0000250|UniProtKB:P27958}.
CC -!- PTM: [Envelope glycoprotein E2]: Highly N-glycosylated.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- PTM: [Protease NS2]: Palmitoylation is required for NS2/3
CC autoprocessing and E2 recruitment to membranes.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- PTM: [Non-structural protein 4B]: Palmitoylated. This modification may
CC play a role in its polymerization or in protein-protein interactions.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- PTM: [Non-structural protein 5A]: Cleaved by host caspases which are
CC probably activated by the viral infection.
CC {ECO:0000269|PubMed:10793006, ECO:0000269|PubMed:16517592}.
CC -!- PTM: [Non-structural protein 5A]: Ubiquitinated (By similarity).
CC Ubiquitination, most probably at Lys-2350, mediated by host IFI27 and
CC SKP2 leads to proteasomal degradation, restricting viral infection (By
CC similarity). {ECO:0000250|UniProtKB:P27958}.
CC -!- PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal
CC form termed p56 (PubMed:7999043, PubMed:7769656). p58 is a
CC hyperphosphorylated form of p56 (PubMed:7999043, PubMed:7769656). p56
CC and p58 coexist in the cell in roughly equivalent amounts
CC (PubMed:7999043). Hyperphosphorylation is dependent on the presence of
CC NS4A (PubMed:7999043). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be
CC responsible for NS5A phosphorylation (By similarity). Phosphorylated
CC NS5A is involved in viral replication (By similarity).
CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000269|PubMed:7769656, ECO:0000269|PubMed:7999043}.
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:25031343}.
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:0000269|PubMed:8396658}.
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; D90208; BAA14233.1; -; Genomic_RNA.
DR EMBL; D89872; BAA14035.1; -; Genomic_RNA.
DR EMBL; D11397; BAA20975.1; -; Genomic_RNA.
DR PIR; A39253; GNWVCJ.
DR PDB; 1DXP; X-ray; 2.40 A; A/B=1027-1213, C/D=1678-1691.
DR PDB; 1DY8; X-ray; 2.40 A; A/B=1027-1213, C/D=1678-1692.
DR PDB; 1DY9; X-ray; 2.10 A; A/B=1027-1213, C/D=1678-1692.
DR PDB; 1W3C; X-ray; 2.30 A; A/B=1027-1213, C/D=1678-1692.
DR PDB; 2K8J; NMR; -; X=781-809.
DR PDB; 3OYP; X-ray; 2.76 A; A/B=1027-1213, C/D=1678-1691.
DR PDB; 3P8N; X-ray; 1.90 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 3P8O; X-ray; 2.30 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 4A1T; X-ray; 2.05 A; A/B=1028-1206, A/B=1678-1690.
DR PDB; 4A1V; X-ray; 2.20 A; A/B=1028-1206, A/B=1678-1690.
DR PDB; 4A1X; X-ray; 1.90 A; A/B=1028-1206.
DR PDB; 4I31; X-ray; 1.93 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 4I32; X-ray; 2.30 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 4I33; X-ray; 1.90 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 4JMY; X-ray; 1.95 A; C/D=1678-1691.
DR PDB; 4KTC; X-ray; 2.30 A; A/C=1028-1213.
DR PDBsum; 1DXP; -.
DR PDBsum; 1DY8; -.
DR PDBsum; 1DY9; -.
DR PDBsum; 1W3C; -.
DR PDBsum; 2K8J; -.
DR PDBsum; 3OYP; -.
DR PDBsum; 3P8N; -.
DR PDBsum; 3P8O; -.
DR PDBsum; 4A1T; -.
DR PDBsum; 4A1V; -.
DR PDBsum; 4A1X; -.
DR PDBsum; 4I31; -.
DR PDBsum; 4I32; -.
DR PDBsum; 4I33; -.
DR PDBsum; 4JMY; -.
DR PDBsum; 4KTC; -.
DR BMRB; P26662; -.
DR SMR; P26662; -.
DR ELM; P26662; -.
DR IntAct; P26662; 5.
DR MINT; P26662; -.
DR BindingDB; P26662; -.
DR ChEMBL; CHEMBL3988603; -.
DR DrugBank; DB01720; (2Z)-2-(Benzoylamino)-3-[4-(2-bromophenoxy)phenyl]acrylic acid.
DR DrugBank; DB04005; Uridine 5'-triphosphate.
DR MEROPS; S29.001; -.
DR GlyGen; P26662; 19 sites.
DR iPTMnet; P26662; -.
DR ABCD; P26662; 7 sequenced antibodies.
DR euHCVdb; D89872; -.
DR euHCVdb; D90208; -.
DR BRENDA; 3.4.21.98; 17002.
DR SABIO-RK; P26662; -.
DR EvolutionaryTrace; P26662; -.
DR Proteomes; UP000008095; Genome.
DR Proteomes; UP000165187; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:AgBase.
DR GO; GO:0044164; C:host cell cytosol; IDA:AgBase.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044186; C:host cell lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:AgBase.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO: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:0032993; C:protein-DNA complex; IMP:CAFA.
DR GO; GO:1990904; C:ribonucleoprotein complex; IMP:CAFA.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IMP:CAFA.
DR GO; GO:1990814; F:DNA/DNA annealing activity; IMP:CAFA.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IMP:CAFA.
DR GO; GO:0003724; F:RNA helicase activity; IDA:CACAO.
DR GO; GO:0033592; F:RNA strand annealing activity; IMP:CAFA.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by 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:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:AgBase.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:AgBase.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0060139; P:positive regulation of apoptotic process by virus; 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:0043489; P:RNA stabilization; IMP:CAFA.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039547; P:suppression by virus of host TRAF activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0019087; P:transformation of host cell by virus; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
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; Disulfide bond;
KW 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; Ribonucleoprotein; RNA-binding;
KW RNA-directed RNA polymerase; Serine protease; Thiol protease;
KW Transcription; Transcription regulation; Transferase; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation;
KW Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW Viral ion channel; Viral nucleoprotein;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250|UniProtKB:P26664"
FT CHAIN 2..3010
FT /note="Genome polyprotein"
FT /id="PRO_0000450855"
FT CHAIN 2..191
FT /note="Core protein precursor"
FT /id="PRO_0000037637"
FT CHAIN 2..177
FT /note="Mature core protein"
FT /id="PRO_0000037638"
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:15163730"
FT /id="PRO_0000037639"
FT CHAIN 192..383
FT /note="Envelope glycoprotein E1"
FT /id="PRO_0000037640"
FT CHAIN 384..746
FT /note="Envelope glycoprotein E2"
FT /id="PRO_0000037641"
FT CHAIN 747..809
FT /note="Viroporin p7"
FT /id="PRO_0000037642"
FT CHAIN 810..1026
FT /note="Protease NS2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT /id="PRO_0000037643"
FT CHAIN 1027..1657
FT /note="Serine protease/helicase NS3"
FT /id="PRO_0000037644"
FT CHAIN 1658..1711
FT /note="Non-structural protein 4A"
FT /id="PRO_0000037645"
FT CHAIN 1712..1972
FT /note="Non-structural protein 4B"
FT /id="PRO_0000037646"
FT CHAIN 1973..2419
FT /note="Non-structural protein 5A"
FT /id="PRO_0000037647"
FT CHAIN 2420..3010
FT /note="RNA-directed RNA polymerase"
FT /id="PRO_0000037648"
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:0000250|UniProtKB:P27958"
FT TRANSMEM 359..379
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 380..725
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 747..757
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TRANSMEM 758..778
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 779..781
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TRANSMEM 782..803
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 804..813
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P27958"
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..1826
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1827..1828
FT /note="Lumenal"
FT /evidence="ECO:0000255"
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..2002
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 2003..2989
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TRANSMEM 2990..3010
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DOMAIN 903..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 2633..2751
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 2..75
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:P27958"
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:0000269|PubMed:17267064"
FT REGION 2..23
FT /note="Interaction with STAT1"
FT /evidence="ECO:0000269|PubMed:16940534"
FT REGION 112..152
FT /note="Important for endoplasmic reticulum and
FT mitochondrial localization"
FT /evidence="ECO:0000269|PubMed:15613354"
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:0000250|UniProtKB:P27958"
FT REGION 265..296
FT /note="Important for fusion"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 385..411
FT /note="HVR1"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 474..482
FT /note="HVR2"
FT /evidence="ECO:0000250|UniProtKB:P27958"
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:0000250|UniProtKB:P27958"
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:0000250|UniProtKB:P27958"
FT REGION 2005..2221
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 2120..2332
FT /note="Transcriptional activation"
FT /evidence="ECO:0000255"
FT REGION 2120..2208
FT /note="FKBP8-binding"
FT /evidence="ECO:0000269|PubMed:16844119"
FT REGION 2135..2139
FT /note="Interaction with non-structural protein 4A"
FT /evidence="ECO:0000269|PubMed:8985418"
FT REGION 2187..2219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2189..2441
FT /note="Interaction with host SKP2"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 2206..2245
FT /note="ISDR"
FT /evidence="ECO:0000269|PubMed:9525599"
FT REGION 2210..2275
FT /note="EIF2AK2/PKR-binding"
FT /evidence="ECO:0000255"
FT REGION 2210..2249
FT /note="ISDR"
FT /evidence="ECO:0000269|PubMed:9525599"
FT REGION 2249..2306
FT /note="NS4B-binding"
FT /evidence="ECO:0000255"
FT REGION 2332..2441
FT /note="Interaction with host IFI27"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 2351..2408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2354..2377
FT /note="V3"
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:0000269|PubMed:23468497,
FT ECO:0000305|PubMed:10793006"
FT COMPBIAS 47..69
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2195..2217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2351..2369
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 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:0000305|PubMed:8392606"
FT ACT_SITE 1083
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT ECO:0000305|PubMed:8389908, ECO:0000305|PubMed:8392606,
FT ECO:0000305|PubMed:9060645"
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:8389908, ECO:0000305|PubMed:8392606"
FT ACT_SITE 1165
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
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:9060645"
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:9060645"
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:9060645"
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:9060645"
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 2639
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 2737
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 SITE 177..178
FT /note="Cleavage; by signal peptide peptidase"
FT /evidence="ECO:0000305|PubMed:15163730"
FT SITE 191..192
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:1648221,
FT ECO:0000269|PubMed:9621068"
FT SITE 383..384
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:1648221"
FT SITE 746..747
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250"
FT SITE 809..810
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:P27958"
FT SITE 1711..1712
FT /note="Cleavage; by serine protease/helicase NS3"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT SITE 1972..1973
FT /note="Cleavage; by serine protease/helicase NS3"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT SITE 2419..2420
FT /note="Cleavage; by serine protease/helicase NS3"
FT /evidence="ECO:0000250|UniProtKB:P27958"
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:0000269|PubMed:7769656"
FT MOD_RES 2197
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000269|PubMed:7769656"
FT MOD_RES 2201
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000269|PubMed:7769656"
FT MOD_RES 2204
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000269|PubMed:7769656"
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 2448
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:25031343"
FT MOD_RES 2461
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:25031343"
FT LIPID 922
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT LIPID 1968
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT LIPID 1972
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 385
FT /note="O-linked (Hex...) threonine; by host"
FT /evidence="ECO:0000305|PubMed:23242014"
FT CARBOHYD 396
FT /note="O-linked (Hex...) threonine; by host"
FT /evidence="ECO:0000269|PubMed:23242014"
FT CARBOHYD 401
FT /note="O-linked (Hex...) serine; by host"
FT /evidence="ECO:0000269|PubMed:23242014"
FT CARBOHYD 404
FT /note="O-linked (Hex...) serine; by host"
FT /evidence="ECO:0000269|PubMed:23242014"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 473
FT /note="O-linked (Hex...) threonine; by host"
FT /evidence="ECO:0000269|PubMed:23242014"
FT CARBOHYD 518
FT /note="O-linked (Hex...) threonine; by host"
FT /evidence="ECO:0000269|PubMed:23242014"
FT CARBOHYD 532
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 576
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 645
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 429..552
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 452..459
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 486..494
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 503..508
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 564..569
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 581..585
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 597..620
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 607..644
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT DISULFID 652..677
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CROSSLNK 2350
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT VARIANT 464
FT /note="E -> K"
FT VARIANT 475..479
FT /note="DMPES -> VVPNI"
FT VARIANT 492
FT /note="R -> Q"
FT VARIANT 522..524
FT /note="FGA -> SGV"
FT VARIANT 538..540
FT /note="LLS -> VLN"
FT VARIANT 580
FT /note="V -> I"
FT VARIANT 608
FT /note="M -> L"
FT VARIANT 622
FT /note="V -> I"
FT VARIANT 626
FT /note="V -> I"
FT VARIANT 674
FT /note="I -> V"
FT VARIANT 694
FT /note="R -> Q"
FT VARIANT 705
FT /note="I -> V"
FT VARIANT 708
FT /note="A -> V"
FT VARIANT 712..713
FT /note="FA -> VV"
FT VARIANT 719
FT /note="I -> V"
FT VARIANT 906
FT /note="I -> M"
FT VARIANT 983
FT /note="L -> I"
FT VARIANT 1140
FT /note="V -> I"
FT VARIANT 1158
FT /note="I -> V"
FT VARIANT 1252
FT /note="L -> R"
FT VARIANT 1297
FT /note="C -> G"
FT VARIANT 1323
FT /note="S -> W"
FT VARIANT 1477
FT /note="L -> V"
FT VARIANT 1485
FT /note="A -> S"
FT VARIANT 1536
FT /note="S -> T"
FT VARIANT 1583
FT /note="L -> F"
FT VARIANT 1635
FT /note="V -> I"
FT VARIANT 1644..1645
FT /note="YI -> FV"
FT VARIANT 1695
FT /note="I -> V"
FT VARIANT 1703
FT /note="Q -> R"
FT VARIANT 1710
FT /note="E -> A"
FT VARIANT 1713
FT /note="S -> P"
FT VARIANT 1753
FT /note="K -> R"
FT VARIANT 1759
FT /note="V -> A"
FT VARIANT 1839
FT /note="V -> I"
FT VARIANT 1873
FT /note="M -> A"
FT VARIANT 1876
FT /note="T -> A"
FT VARIANT 1896
FT /note="V -> I"
FT VARIANT 1978
FT /note="K -> R"
FT VARIANT 1989
FT /note="S -> T"
FT VARIANT 2002
FT /note="R -> K"
FT VARIANT 2006
FT /note="L -> V"
FT VARIANT 2009
FT /note="L -> F"
FT VARIANT 2093
FT /note="V -> I"
FT VARIANT 2125
FT /note="V -> L"
FT VARIANT 2136..2138
FT /note="VCK -> ACR"
FT VARIANT 2143..2146
FT /note="EEVV -> VDVT"
FT VARIANT 2190
FT /note="L -> P"
FT VARIANT 2196
FT /note="P -> S"
FT VARIANT 2199
FT /note="A -> G"
FT VARIANT 2199
FT /note="A -> V"
FT VARIANT 2200
FT /note="S -> T"
FT VARIANT 2204
FT /note="S -> R"
FT VARIANT 2205
FT /note="Q -> H"
FT VARIANT 2208
FT /note="A -> T"
FT VARIANT 2209
FT /note="P -> H"
FT VARIANT 2209
FT /note="P -> L"
FT VARIANT 2209
FT /note="P -> S"
FT VARIANT 2210
FT /note="S -> P"
FT VARIANT 2211
FT /note="L -> S"
FT VARIANT 2212
FT /note="K -> E"
FT VARIANT 2212
FT /note="K -> R"
FT VARIANT 2214
FT /note="T -> A"
FT VARIANT 2215
FT /note="C -> Y"
FT VARIANT 2216
FT /note="T -> I"
FT VARIANT 2217
FT /note="T -> A"
FT VARIANT 2218
FT /note="H -> A"
FT VARIANT 2218
FT /note="H -> L"
FT VARIANT 2218
FT /note="H -> Q"
FT VARIANT 2218
FT /note="H -> R"
FT VARIANT 2218
FT /note="H -> T"
FT VARIANT 2219
FT /note="H -> R"
FT VARIANT 2219
FT /note="H -> Y"
FT VARIANT 2220
FT /note="D -> G"
FT VARIANT 2222
FT /note="P -> L"
FT VARIANT 2222
FT /note="P -> S"
FT VARIANT 2223
FT /note="D -> G"
FT VARIANT 2224
FT /note="A -> V"
FT VARIANT 2225
FT /note="D -> G"
FT VARIANT 2225
FT /note="D -> N"
FT VARIANT 2227
FT /note="I -> V"
FT VARIANT 2228
FT /note="E -> A"
FT VARIANT 2228
FT /note="E -> D"
FT VARIANT 2228
FT /note="E -> G"
FT VARIANT 2228
FT /note="E -> K"
FT VARIANT 2230
FT /note="N -> D"
FT VARIANT 2230
FT /note="N -> S"
FT VARIANT 2233
FT /note="W -> R"
FT VARIANT 2259
FT /note="I -> L"
FT VARIANT 2262
FT /note="V -> E"
FT VARIANT 2268
FT /note="I -> V"
FT VARIANT 2271
FT /note="P -> A"
FT VARIANT 2278..2279
FT /note="PR -> SK"
FT VARIANT 2303
FT /note="D -> S"
FT VARIANT 2310
FT /note="V -> A"
FT VARIANT 2318..2321
FT /note="STKA -> PTTG"
FT VARIANT 2329
FT /note="R -> K"
FT VARIANT 2367
FT /note="G -> A"
FT VARIANT 2372
FT /note="A -> T"
FT VARIANT 2379
FT /note="G -> E"
FT VARIANT 2382
FT /note="V -> I"
FT VARIANT 2414..2416
FT /note="EDV -> DDI"
FT VARIANT 2673
FT /note="R -> K"
FT VARIANT 2681
FT /note="V -> I"
FT VARIANT 2754
FT /note="A -> S"
FT VARIANT 2757
FT /note="A -> V"
FT VARIANT 2950
FT /note="K -> R"
FT MUTAGEN 139
FT /note="L->A: Complete loss of core protein processing by
FT host signal peptidase, no effect on the cleavage at core-E1
FT junction; when associated with A-140 and A-144."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 140
FT /note="V->A: Complete loss of core protein processing by
FT host signal peptidase, no effect on the cleavage at core-E1
FT junction; when associated with A-139 and A-144."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 144
FT /note="L->A: Complete loss of core protein processing by
FT host signal peptidase, no effect on the cleavage at core-E1
FT junction; when associated with A-139 and A-140."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 176..177
FT /note="IF->AL: Complete loss of core protein processing by
FT host signal peptidase."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 178..179
FT /note="LL->VV: No effect on processing of the core
FT protein."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 181..182
FT /note="LL->VV: No effect on processing of the core
FT protein."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 183..184
FT /note="SC->LA: No effect on processing of the core
FT protein."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 183..184
FT /note="SC->LV: No effect on processing of the core
FT protein."
FT /evidence="ECO:0000269|PubMed:15163730"
FT MUTAGEN 922
FT /note="C->A: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 932
FT /note="H->A: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 952
FT /note="H->A,R: Complete loss of protease NS2 activity."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 972
FT /note="E->Q: Reduced protease NS2 activity."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 980
FT /note="E->Q: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 993
FT /note="C->A: Complete loss of protease NS2 activity."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1009
FT /note="E->Q: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1042
FT /note="C->A: No effect on zinc-binding by serine protease
FT NS3."
FT /evidence="ECO:0000269|PubMed:9060645"
FT MUTAGEN 1058
FT /note="E->Q: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1073
FT /note="C->S: No effect on zinc-binding by serine protease
FT NS3."
FT /evidence="ECO:0000269|PubMed:9060645"
FT MUTAGEN 1078
FT /note="C->L: No effect on zinc-binding by serine protease
FT NS3."
FT /evidence="ECO:0000269|PubMed:9060645"
FT MUTAGEN 1083
FT /note="H->A: Complete loss of serine protease NS3 activity.
FT No effect on zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8389908,
FT ECO:0000269|PubMed:8392606, ECO:0000269|PubMed:9060645"
FT MUTAGEN 1107
FT /note="D->A: Complete loss of serine protease NS3
FT activity."
FT /evidence="ECO:0000269|PubMed:8389908,
FT ECO:0000269|PubMed:8392606"
FT MUTAGEN 1123
FT /note="C->A: Reduced protease NS2 and serine protease NS3
FT activities."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1125
FT /note="C->A: Reduced protease NS2 and serine protease NS3
FT activities."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1136
FT /note="H->A: No effect on polyprotein processing. No effect
FT on zinc-binding by serine protease/helicase NS3."
FT /evidence="ECO:0000269|PubMed:8392606,
FT ECO:0000269|PubMed:9060645"
FT MUTAGEN 1165
FT /note="S->A: Complete loss of serine protease NS3 activity.
FT No effect on zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8389908,
FT ECO:0000269|PubMed:8392606, ECO:0000269|PubMed:9060645"
FT MUTAGEN 1171
FT /note="C->A: Reduced protease NS2 and serine protease NS3
FT activities."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1175
FT /note="H->A: No effect on polyprotein processing. Reduces
FT zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8392606,
FT ECO:0000269|PubMed:9060645"
FT MUTAGEN 1185
FT /note="C->A: No effect on polyprotein processing. No effect
FT on zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8392606,
FT ECO:0000269|PubMed:9060645"
FT MUTAGEN 1199
FT /note="E->Q: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1202
FT /note="E->Q: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:8392606"
FT MUTAGEN 1227
FT /note="H->A: No effect on polyprotein processing. No effect
FT on zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8392606,
FT ECO:0000269|PubMed:9060645"
FT MUTAGEN 1229
FT /note="H->A: No effect on polyprotein processing. No effect
FT on zinc-binding by serine protease NS3."
FT /evidence="ECO:0000269|PubMed:8392606,
FT ECO:0000269|PubMed:9060645"
FT MUTAGEN 2126
FT /note="D->E: Complete loss of nuclear translocation of
FT NS5A."
FT /evidence="ECO:0000269|PubMed:23468497"
FT MUTAGEN 2194
FT /note="S->A: No effect on NS5A hyperphosphorylation and on
FT down-regulation of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2194
FT /note="S->D: No effect on down-regulation of viral
FT translation."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2197
FT /note="S->A: Loss of NS5A hyperphosphorylation; no effect
FT on down-regulation of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2197
FT /note="S->D: No effect on down-regulation of viral
FT translation."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2200
FT /note="S->A: No effect on NS5A hyperphosphorylation."
FT /evidence="ECO:0000269|PubMed:7769656"
FT MUTAGEN 2201
FT /note="S->A: Loss of NS5A hyperphosphorylation. Complete
FT loss of NS5A-induced down-regulation of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2201
FT /note="S->D: No effect on down-regulation of viral
FT translation; increased NS5A dimerization."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2202
FT /note="S->A: No effect on NS5A hyperphosphorylation."
FT /evidence="ECO:0000269|PubMed:7769656"
FT MUTAGEN 2204
FT /note="S->A: Loss of NS5A hyperphosphorylation. No effect
FT on down-regulation of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2204
FT /note="S->D: Complete loss of NS5A-induced down-regulation
FT of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2207
FT /note="S->A: No effect on NS5A hyperphosphorylation. No
FT effect on down-regulation of viral translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2207
FT /note="S->D: No effect on down-regulation of viral
FT translation."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2210
FT /note="S->A: No effect on NS5A hyperphosphorylation.
FT Complete loss of NS5A-induced down-regulation of viral
FT translation."
FT /evidence="ECO:0000269|PubMed:31585734,
FT ECO:0000269|PubMed:7769656"
FT MUTAGEN 2210
FT /note="S->D: No effect on down-regulation of viral
FT translation; increased NS5A dimerization."
FT /evidence="ECO:0000269|PubMed:31585734"
FT MUTAGEN 2221
FT /note="S->A: No effect on NS5A hyperphosphorylation."
FT /evidence="ECO:0000269|PubMed:7769656"
FT MUTAGEN 2448
FT /note="S->A: Partial loss of RNA-directed RNA polymerase
FT phosphorylation. 60% loss of viral RNA replication."
FT /evidence="ECO:0000269|PubMed:25031343"
FT MUTAGEN 2461
FT /note="S->A: Partial loss of RNA-directed RNA polymerase
FT phosphorylation. 30% loss of viral RNA replication."
FT /evidence="ECO:0000269|PubMed:25031343"
FT HELIX 786..801
FT /evidence="ECO:0007829|PDB:2K8J"
FT STRAND 1030..1035
FT /evidence="ECO:0007829|PDB:3P8N"
FT HELIX 1039..1048
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1057..1063
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1068..1074
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1077..1080
FT /evidence="ECO:0007829|PDB:3P8N"
FT HELIX 1082..1085
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1090..1092
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1095..1097
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1100..1103
FT /evidence="ECO:0007829|PDB:3P8N"
FT TURN 1104..1107
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1108..1112
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1128..1133
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1139..1144
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1146..1157
FT /evidence="ECO:0007829|PDB:3P8N"
FT HELIX 1158..1161
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1168..1170
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1176..1186
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1189..1197
FT /evidence="ECO:0007829|PDB:3P8N"
FT HELIX 1198..1206
FT /evidence="ECO:0007829|PDB:3P8N"
FT STRAND 1680..1689
FT /evidence="ECO:0007829|PDB:3P8N"
SQ SEQUENCE 3010 AA; 327021 MW; AA993794F46DB185 CRC64;
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG
RRQPIPKARR PEGRTWAQPG YPWPLYGNEG MGWAGWLLSP RGSRPSWGPT DPRRRSRNLG
KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA
LLSCLTIPAS AYEVRNVSGI YHVTNDCSNS SIVYEAADMI MHTPGCVPCV RESNFSRCWV
ALTPTLAARN SSIPTTTIRR HVDLLVGAAA LCSAMYVGDL CGSVFLVSQL FTFSPRRYET
VQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG AHWGVLAGLA
YYSMVGNWAK VLIVMLLFAG VDGHTHVTGG RVASSTQSLV SWLSQGPSQK IQLVNTNGSW
HINRTALNCN DSLQTGFIAA LFYAHRFNAS GCPERMASCR PIDEFAQGWG PITHDMPESS
DQRPYCWHYA PRPCGIVPAS QVCGPVYCFT PSPVVVGTTD RFGAPTYSWG ENETDVLLLS
NTRPPQGNWF GCTWMNSTGF TKTCGGPPCN IGGVGNNTLV CPTDCFRKHP EATYTKCGSG
PWLTPRCMVD YPYRLWHYPC TVNFTVFKVR MYVGGVEHRL NAACNWTRGE RCDLEDRDRS
ELSPLLLSTT EWQILPCSFT TLPALSTGLI HLHRNIVDVQ YLYGIGSAVV SFAIKWEYIL
LLFLLLADAR VCACLWMMLL IAQAEATLEN LVVLNAASVA GAHGLLSFLV FFCAAWYIKG
RLVPGAAYAL YGVWPLLLLL LALPPRAYAM DREMAASCGG AVFVGLVLLT LSPYYKVFLA
RLIWWLQYFI TRAEAHLQVW VPPLNVRGGR DAIILLTCAV HPELIFDITK LLLAILGPLM
VLQAGITRVP YFVRAQGLIR ACMLVRKVAG GHYVQMAFMK LAALTGTYVY DHLTPLRDWA
HAGLRDLAVA VEPVVFSDME TKLITWGADT AACGDIISGL PVSARRGKEI LLGPADSFGE
QGWRLLAPIT AYSQQTRGLL GCIITSLTGR DKNQVDGEVQ VLSTATQSFL ATCVNGVCWT
VYHGAGSKTL AGPKGPITQM YTNVDQDLVG WPAPPGARSM TPCTCGSSDL YLVTRHADVV
PVRRRGDSRG SLLSPRPISY LKGSSGGPLL CPSGHVVGIF RAAVCTRGVA KAVDFIPVES
METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK VLVLNPSVAA
TLGFGAYMSK AHGIEPNIRT GVRTITTGGP ITYSTYCKFL ADGGCSGGAY DIIICDECHS
TDSTTILGIG TVLDQAETAG ARLVVLATAT PPGSITVPHP NIEEVALSNT GEIPFYGKAI
PIEAIKGGRH LIFCHSKKKC DELAAKLTGL GLNAVAYYRG LDVSVIPTSG DVVVVATDAL
MTGFTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRAQRRGR TGRGRSGIYR
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV CQDHLEFWES
VFTGLTHIDA HFLSQTKQAG DNLPYLVAYQ ATVCARAQAP PPSWDQMWKC LIRLKPTLHG
PTPLLYRLGA VQNEVTLTHP ITKYIMACMS ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV
VIVGRIILSG RPAVIPDREV LYQEFDEMEE CASHLPYIEQ GMQLAEQFKQ KALGLLQTAT
KQAEAAAPVV ESKWRALEVF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP
LTTQNTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD ILAGYGAGVA
GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA ILRRHVGPGE GAVQWMNRLI
AFASRGNHVS PTHYVPESDA AARVTQILSS LTITQLLKRL HQWINEDCST PCSGSWLKDV
WDWICTVLSD FKTWLQSKLL PRLPGLPFLS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK
NGSMRIVGPK TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH
YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPVCKPL LREEVVFQVG LNQYLVGSQL
PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS SSASQLSAPS LKATCTTHHD
SPDADLIEAN LLWRQEMGGN ITRVESENKV VILDSFDPIR AVEDEREISV PAEILRKPRK
FPPALPIWAR PDYNPPLLES WKDPDYVPPV VHGCPLPSTK APPIPPPRRK RTVVLTESTV
SSALAELATK TFGSSGSSAV DSGTATGPPD QASDDGDKGS DVESYSSMPP LEGEPGDPDL
SDGSWSTVSG EAGEDVVCCS MSYTWTGALI TPCAAEESKL PINPLSNSLL RHHSMVYSTT
SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAR LLSIEEACKL TPPHSAKSKF
GYGAKDVRSL SSRAVNHIRS VWEDLLEDTE TPIDTTIMAK NEVFCVQPEK GGRKPARLIV
FPDLGVRVCE KMALYDVVST LPQAVMGPSY GFQYSPGQRV EFLVNTWKSK KCPMGFSYDT
RCFDSTVTEN DIRTEESIYQ CCDLAPEARQ AIRSLTERLY VGGPLTNSKG QNCGYRRCRA
SGVLTTSCGN TLTCYLKATA ACRAAKLQDC TMLVNGDDLV VICESAGTQE DAAALRAFTE
AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV YYLTRDPTTP LARAAWETVR
HTPVNSWLGN IIMYAPTLWA RMILMTHFFS ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ
IIERLHGLSA FSLHSYSPGE INRVASCLRK LGVPPLRVWR HRARSVRAKL LSQGGRAATC
GKYLFNWAVK TKLKLTPIPA ASQLDLSGWF VAGYNGGDIY HSLSRARPRW FMLCLLLLSV
GVGIYLLPNR
