ID POLG_HCVBK Reviewed; 3010 AA.
AC P26663;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 235.
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:0000269|PubMed:11591719, ECO:0000269|PubMed:9261354};
DE Contains:
DE RecName: Full=Serine protease/helicase NS3;
DE EC=3.4.21.98 {ECO:0000250|UniProtKB:P27958};
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:P27958};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:P27958};
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:20194503, ECO:0000269|PubMed:9343198};
DE AltName: Full=NS5B;
DE AltName: Full=p68;
OS Hepatitis C virus genotype 1b (isolate BK) (HCV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Hepacivirus; Hepacivirus hominis.
OX NCBI_TaxID=11105;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1847440; DOI=10.1128/jvi.65.3.1105-1113.1991;
RA Takamizawa A., Mori C., Fuke I., Manabe S., Murakami S., Fujita J.,
RA Onishi E., Andoh T., Yoshida I., Okayama H.;
RT "Structure and organization of the hepatitis C virus genome isolated from
RT human carriers.";
RL J. Virol. 65:1105-1113(1991).
RN [2]
RP PROTEIN SEQUENCE OF 1487-1500.
RX PubMed=8647104; DOI=10.1111/j.1432-1033.1996.0611p.x;
RA Borowski P., Heiland M., Oehlmann K., Becker B., Korneteky L.;
RT "Non-structural protein 3 of hepatitis C virus inhibits phosphorylation
RT mediated by cAMP-dependent protein kinase.";
RL Eur. J. Biochem. 237:611-618(1996).
RN [3]
RP SUBCELLULAR LOCATION (MATURE CORE PROTEIN), RNA-BINDING ACTIVITY (MATURE
RP CORE PROTEIN), AND FUNCTION (MATURE CORE PROTEIN).
RX PubMed=8189501; DOI=10.1128/jvi.68.6.3631-3641.1994;
RA Santolini E., Migliaccio G., La Monica N.;
RT "Biosynthesis and biochemical properties of the hepatitis C virus core
RT protein.";
RL J. Virol. 68:3631-3641(1994).
RN [4]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), AND GLYCOSYLATION AT ASN-196.
RX PubMed=8862403; DOI=10.1006/viro.1996.0510;
RA Huessy P., Langen H., Mous J., Jacobsen H.;
RT "Hepatitis C virus core protein: carboxy-terminal boundaries of two
RT processed species suggest cleavage by a signal peptide peptidase.";
RL Virology 224:93-104(1996).
RN [5]
RP FUNCTION (PROTEASE NS2), PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN),
RP CATALYTIC ACTIVITY (PROTEASE NS2), BIOPHYSICOCHEMICAL PROPERTIES (PROTEASE
RP NS2), DOMAIN (PROTEASE NS2), AND DOMAIN (SERINE PROTEASE/HELICASE NS3).
RX PubMed=9261354; DOI=10.1128/jvi.71.9.6373-6380.1997;
RA Pieroni L., Santolini E., Fipaldini C., Pacini L., Migliaccio G.,
RA La Monica N.;
RT "In vitro study of the NS2-3 protease of hepatitis C virus.";
RL J. Virol. 71:6373-6380(1997).
RN [6]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE), CATALYTIC ACTIVITY (RNA-DIRECTED
RP RNA POLYMERASE), AND MUTAGENESIS OF ASP-2639; ASP-2644; GLY-2702; THR-2705;
RP THR-2706; ASN-2710; ASP-2737 AND ASP-2738.
RX PubMed=9343198; DOI=10.1128/jvi.71.11.8416-8428.1997;
RA Lohmann V., Koerner F., Herian U., Bartenschlager R.;
RT "Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA
RT polymerase and identification of amino acid sequence motifs essential for
RT enzymatic activity.";
RL J. Virol. 71:8416-8428(1997).
RN [7]
RP FUNCTION (NON-STRUCTURAL PROTEIN 5A), INTERACTION WITH HOST EIF2AK2/PKR
RP (NON-STRUCTURAL PROTEIN 5A), AND DOMAIN (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=9710605; DOI=10.1128/mcb.18.9.5208;
RA Gale M.J. Jr., Blakely C.M., Kwieciszewski B., Tan S.-L., Dossett M.,
RA Tang N.M., Korth M.J., Polyak S.J., Gretch D.R., Katze M.G.;
RT "Control of PKR protein kinase by hepatitis C virus nonstructural 5A
RT protein: molecular mechanisms of kinase regulation.";
RL Mol. Cell. Biol. 18:5208-5218(1998).
RN [8]
RP INTERACTION WITH HOST GRB2 (NON-STRUCTURAL PROTEIN 5A), AND MUTAGENESIS OF
RP PRO-2322; PRO-2323 AND PRO-2326.
RX PubMed=10318918; DOI=10.1073/pnas.96.10.5533;
RA Tan S.-L., Nakao H., He Y., Vijaysri S., Neddermann P., Jacobs B.L.,
RA Mayer B.J., Katze M.G.;
RT "NS5A, a nonstructural protein of hepatitis C virus, binds growth factor
RT receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-
RT dependent manner and perturbs mitogenic signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:5533-5538(1999).
RN [9]
RP PHOSPHORYLATION AT SER-2194, AND MUTAGENESIS OF SER-2194.
RX PubMed=11118372; DOI=10.1006/viro.2000.0662;
RA Katze M.G., Kwieciszewski B., Goodlett D.R., Blakely C.M., Neddermann P.,
RA Tan S.-L., Aebersold R.;
RT "Ser(2194) is a highly conserved major phosphorylation site of the
RT hepatitis C virus nonstructural protein NS5A.";
RL Virology 278:501-513(2000).
RN [10]
RP COFACTOR (PROTEASE NS2), CATALYTIC ACTIVITY (PROTEASE NS2), PROTEOLYTIC
RP CLEAVAGE (GENOME POLYPROTEIN), DOMAIN (SERINE PROTEASE/HELICASE NS3), AND
RP DOMAIN (PROTEASE NS2).
RX PubMed=11591719; DOI=10.1074/jbc.m108266200;
RA Thibeault D., Maurice R., Pilote L., Lamarre D., Pause A.;
RT "In vitro characterization of a purified NS2/3 protease variant of
RT hepatitis C virus.";
RL J. Biol. Chem. 276:46678-46684(2001).
RN [11]
RP INTERACTION WITH HOST PIK3R1 (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=12186904; DOI=10.1128/jvi.76.18.9207-9217.2002;
RA He Y., Nakao H., Tan S.-L., Polyak S.J., Neddermann P., Vijaysri S.,
RA Jacobs B.L., Katze M.G.;
RT "Subversion of cell signaling pathways by hepatitis C virus nonstructural
RT 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-
RT kinase.";
RL J. Virol. 76:9207-9217(2002).
RN [12]
RP DOMAIN (ENVELOPE GLYCOPROTEIN E2).
RX PubMed=12660945; DOI=10.1086/368221;
RA Hofmann W.P., Sarrazin C., Kronenberger B., Schonberger B., Bruch K.,
RA Zeuzem S.;
RT "Mutations within the CD81-binding sites and hypervariable region 2 of the
RT envelope 2 protein: correlation with treatment response in hepatitis C
RT virus-infected patients.";
RL J. Infect. Dis. 187:982-987(2003).
RN [13]
RP PHOSPHORYLATION (NON-STRUCTURAL PROTEIN 5A).
RX PubMed=15016873; DOI=10.1128/jvi.78.7.3502-3513.2004;
RA Coito C., Diamond D.L., Neddermann P., Korth M.J., Katze M.G.;
RT "High-throughput screening of the yeast kinome: identification of human
RT serine/threonine protein kinases that phosphorylate the hepatitis C virus
RT NS5A protein.";
RL J. Virol. 78:3502-3513(2004).
RN [14]
RP PHOSPHORYLATION BY HOST CSNK1A1 (NON-STRUCTURAL PROTEIN 5A).
RC STRAIN=Isolate HCV-AT;
RX PubMed=16943283; DOI=10.1128/jvi.01465-06;
RA Quintavalle M., Sambucini S., Di Pietro C., De Francesco R., Neddermann P.;
RT "The alpha isoform of protein kinase CKI is responsible for hepatitis C
RT virus NS5A hyperphosphorylation.";
RL J. Virol. 80:11305-11312(2006).
RN [15]
RP SUBCELLULAR LOCATION (MATURE CORE PROTEIN).
RX PubMed=17188392; DOI=10.1016/j.jhep.2006.10.019;
RA Jackel-Cram C., Babiuk L.A., Liu Q.;
RT "Up-regulation of fatty acid synthase promoter by hepatitis C virus core
RT protein: genotype-3a core has a stronger effect than genotype-1b core.";
RL J. Hepatol. 46:999-1008(2007).
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 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 [18]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE), AND CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE).
RX PubMed=20194503; DOI=10.1074/jbc.m109.082206;
RA Reich S., Golbik R.P., Geissler R., Lilie H., Behrens S.E.;
RT "Mechanisms of activity and inhibition of the hepatitis C virus RNA-
RT dependent RNA polymerase.";
RL J. Biol. Chem. 285:13685-13693(2010).
RN [19] {ECO:0007744|PDB:1A1Q}
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1027-1215 IN COMPLEX WITH ZINC,
RP ACTIVE SITE (SERINE PROTEASE/HELICASE NS3), AND COFACTOR (SERINE
RP PROTEASE/HELICASE NS3).
RX PubMed=8861916; DOI=10.1016/s0092-8674(00)81350-1;
RA Love R.A., Parge H.E., Wickersham J.A., Hostomsky Z., Habuka N.,
RA Moomaw E.W., Adachi T., Hostomska Z.;
RT "The crystal structure of hepatitis C virus NS3 proteinase reveals a
RT trypsin-like fold and a structural zinc binding site.";
RL Cell 87:331-342(1996).
RN [20] {ECO:0007744|PDB:1JXP, ECO:0007744|PDB:1NS3}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1027-1206 AND 1678-1691,
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 4A (SERINE PROTEASE/HELICASE NS3),
RP INTERACTION WITH SERINE PROTEASE/HELICASE NS3 (NON-STRUCTURAL PROTEIN 4A),
RP AND ACTIVE SITE (SERINE PROTEASE/HELICASE NS3).
RX PubMed=9568891; DOI=10.1002/pro.5560070402;
RA Yan Y., Li Y., Munshi S., Sardana V., Cole J.L., Sardana M.,
RA Steinkuehler C., Tomei L., de Francesco R., Kuo L.C., Chen Z.;
RT "Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a
RT 2.2-A resolution structure in a hexagonal crystal form.";
RL Protein Sci. 7:837-847(1998).
RN [21] {ECO:0007744|PDB:8OHM}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1216-1650, DOMAIN (SERINE
RP PROTEASE/HELICASE NS3), RNA-BINDING (SERINE PROTEASE/HELICASE NS3), AND
RP FUNCTION (SERINE PROTEASE/HELICASE NS3).
RX PubMed=9614113; DOI=10.1074/jbc.273.24.15045;
RA Cho H.-S., Ha N.-C., Kang L.-W., Chung K.M., Back S.H., Jang S.K.,
RA Oh B.-H.;
RT "Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A
RT feasible mechanism of unwinding duplex RNA.";
RL J. Biol. Chem. 273:15045-15052(1998).
RN [22] {ECO:0007744|PDB:1CU1}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1013-1657.
RX PubMed=10574797; DOI=10.1016/s0969-2126(00)80025-8;
RA Yao N., Reichert P., Taremi S.S., Prosise W.W., Weber P.C.;
RT "Molecular views of viral polyprotein processing revealed by the crystal
RT structure of the hepatitis C virus bifunctional protease-helicase.";
RL Structure 7:1353-1363(1999).
RN [23] {ECO:0007744|PDB:1BT7}
RP STRUCTURE BY NMR OF 1027-1206 IN COMPLEX WITH ZINC, INTERACTION WITH
RP NON-STRUCTURAL PROTEIN 4A (SERINE PROTEASE/HELICASE NS3), AND INTERACTION
RP WITH SERINE PROTEASE/HELICASE NS3 (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=10366511; DOI=10.1006/jmbi.1999.2745;
RA Barbato G., Cicero D.O., Nardi M.C., Steinkuehler C., Cortese R.,
RA De Francesco R., Bazzo R.;
RT "The solution structure of the N-terminal proteinase domain of the
RT hepatitis C virus (HCV) NS3 protein provides new insights into its
RT activation and catalytic mechanism.";
RL J. Mol. Biol. 289:371-384(1999).
RN [24] {ECO:0007744|PDB:1CSJ}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2420-2950.
RX PubMed=10557268; DOI=10.1073/pnas.96.23.13034;
RA Bressanelli S., Tomei L., Roussel A., Incitti I., Vitale R.L., Mathieu M.,
RA De Francesco R., Rey F.A.;
RT "Crystal structure of the RNA-dependent RNA polymerase of hepatitis C
RT virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:13034-13039(1999).
RN [25] {ECO:0007744|PDB:1C2P}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2414-2989.
RX PubMed=10504728; DOI=10.1038/13305;
RA Lesburg C.A., Cable M.B., Ferrari E., Hong Z., Mannarino A.F., Weber P.C.;
RT "Crystal structure of the RNA-dependent RNA polymerase from hepatitis C
RT virus reveals a fully encircled active site.";
RL Nat. Struct. Biol. 6:937-943(1999).
RN [26] {ECO:0007744|PDB:1QUV}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2420-2999.
RX PubMed=10574802; DOI=10.1016/s0969-2126(00)80031-3;
RA Ago H., Adachi T., Yoshida A., Yamamoto M., Habuka N., Yatsunami K.,
RA Miyano M.;
RT "Crystal structure of the RNA-dependent RNA polymerase of hepatitis C
RT virus.";
RL Structure 7:1417-1426(1999).
RN [27] {ECO:0007744|PDB:1GX5, ECO:0007744|PDB:1GX6}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2420-2955 IN COMPLEX WITH GTP AND
RP MANGANESE, AND COFACTOR.
RX PubMed=11884572; DOI=10.1128/jvi.76.7.3482-3492.2002;
RA Bressanelli S., Tomei L., Rey F.A., De Francesco R.;
RT "Structural analysis of the hepatitis C virus RNA polymerase in complex
RT with ribonucleotides.";
RL J. Virol. 76:3482-3492(2002).
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 (Probable). Modulates viral translation
CC initiation by interacting with viral IRES and 40S ribosomal subunit (By
CC similarity). Affects various cell signaling pathways, host immunity and
CC lipid metabolism (Probable). Prevents the establishment of cellular
CC antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta)
CC and IFN-gamma signaling pathways and by blocking the formation of
CC phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-
CC dependent degradation of STAT1 (By similarity). Activates STAT3 leading
CC to cellular transformation (By similarity). Regulates the activity of
CC cellular genes, including c-myc and c-fos (By similarity). May repress
CC the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in
CC the cytoplasm (By similarity). Represses cell cycle negative regulating
CC factor CDKN1A, thereby interrupting an important check point of normal
CC cell 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:P26662,
CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8,
CC ECO:0000305, ECO:0000305|PubMed:8189501}.
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 (By similarity). 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:0000305}.
CC -!- FUNCTION: [Protease NS2]: Cysteine protease required for the
CC proteolytic auto-cleavage between the non-structural proteins NS2 and
CC NS3 (Probable) (PubMed:11591719). The N-terminus of NS3 is required for
CC the function of NS2 protease (active region NS2-3) (PubMed:11591719).
CC Promotes the initiation of viral particle assembly by mediating the
CC interaction between structural and non-structural proteins (By
CC similarity). {ECO:0000250|UniProtKB:Q9WMX2,
CC ECO:0000269|PubMed:11591719, ECO:0000305|PubMed:9261354}.
CC -!- FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic
CC activities: serine protease with a chymotrypsin-like fold, NTPase and
CC RNA helicase (PubMed:9614113). 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 ECO:0000269|PubMed:9614113}.
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 (By similarity). Zinc is
CC essential for RNA-binding (By similarity). Participates in the viral
CC particle production as a result of its interaction with the viral
CC mature core protein (By similarity). Its interaction with host VAPB may
CC target the viral replication complex to vesicles. Down-regulates viral
CC IRES translation initiation (By similarity). Mediates interferon
CC resistance, presumably by interacting with and inhibiting host
CC 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 (By
CC similarity). Via the interaction with host PACSIN2, modulates lipid
CC droplet formation in order to promote virion assembly (By similarity).
CC Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By
CC similarity). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase
CC that performs primer-template recognition and RNA synthesis during
CC viral replication. Initiates RNA transcription/replication at a flavin
CC adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs.
CC In this way, recognition of viral 5' RNA by host pattern recognition
CC receptors can be bypassed, thereby evading activation of antiviral
CC pathways. {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:0000250|UniProtKB:P27958};
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:0000250|UniProtKB:P27958};
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:0000250|UniProtKB:P27958};
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:20194503, ECO:0000269|PubMed:9343198};
CC -!- COFACTOR: [Protease NS2]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11591719};
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:0000305|PubMed:11591719};
CC -!- COFACTOR: [Serine protease/helicase NS3]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:8861916};
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:8861916). The
CC magnesium ion is essential for the helicase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9WMX2, ECO:0000269|PubMed:8861916};
CC -!- COFACTOR: [RNA-directed RNA polymerase]:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:11884572};
CC Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal
CC center. {ECO:0000305|PubMed:11884572};
CC -!- ACTIVITY REGULATION: Inhibited by the antiviral drug hexamethylene
CC amiloride (By similarity). Inhibition by amantadine appears to be
CC genotype-dependent (By similarity). Also inhibited by long-alkyl-chain
CC iminosugar derivatives (By similarity). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000250|UniProtKB:P27958}.
CC -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Activity is up-
CC regulated by PRK2/PKN2-mediated phosphorylation.
CC {ECO:0000250|UniProtKB:P27958}.
CC -!- ACTIVITY REGULATION: [Protease NS2]: Activity of auto-protease NS2 is
CC dependent on zinc ions and completely inhibited by EDTA, 1,10-
CC phenanthroline, iodocetamide and N-ethylmaleimide. According to
CC PubMed:9261354, completely inhibited by the serine protease inhibitors
CC TLCK and TPCK (PubMed:9261354). According to PubMed:8189501, almost
CC completely inhibited by TPCK and slightly inhibited by TLCK. Not
CC inhibited by antipain, aprotinin, E64, PMSF and pepstatin. Also
CC inhibited by NS2 and NS4A derived peptides. Serine protease/helicase
CC NS3 is also activated by zinc ions. {ECO:0000269|PubMed:9261354}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Protease NS2]:
CC Temperature dependence:
CC Optimum temperature is 20 degrees Celsius.
CC {ECO:0000269|PubMed:9261354};
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 (By
CC similarity). Interacts with host STAT3; this interaction constitutively
CC activates STAT3 (By similarity). Associates with host LTBR receptor (By
CC similarity). Interacts with host TNFRSF1A receptor and possibly induces
CC apoptosis (By similarity). Interacts with host HNRPK (By similarity).
CC Interacts with host YWHAE (By similarity). Interacts with host
CC UBE3A/E6AP (By similarity). Interacts with host DDX3X (By similarity).
CC Interacts with host APOA2 (By similarity). Interacts with host RXRA
CC protein (By similarity). Interacts with host SP110 isoform 3/Sp110b;
CC this interaction sequesters the transcriptional corepressor SP110 away
CC from the nucleus (By similarity). Interacts with host CREB3 nuclear
CC transcription protein; this interaction triggers cell transformation
CC (By similarity). Interacts with host ACY3 (By similarity). Interacts
CC with host C1QR1 (By similarity). Interacts with host RBM24; this
CC interaction, which enhances the interaction of the mature core protein
CC with 5'-UTR, may inhibit viral translation and favor replication (By
CC similarity). Interacts (via N-terminus) with host EIF2AK2/PKR (via N-
CC terminus); this interaction induces the autophosphorylation of EIF2AK2
CC (By similarity). Part of the viral assembly initiation complex composed
CC of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By
CC similarity). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846,
CC ECO:0000250|UniProtKB:Q03463, ECO:0000250|UniProtKB:Q5EG65,
CC ECO:0000250|UniProtKB:Q99IB8}.
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). Interacts with host NEURL3; this
CC interaction prevents E1 binding to glycoprotein E2 (By similarity).
CC {ECO:0000250|UniProtKB:P27958, 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
CC (PubMed:9568891, PubMed:10366511). NS3-NS4A interaction is essential
CC for NS3 activation and allows membrane anchorage of the latter
CC (PubMed:9568891). NS3/NS4A complex also prevents phosphorylation of
CC host IRF3, thus preventing the establishment of dsRNA induced antiviral
CC state (By similarity). Interacts with host MAVS; this interaction leads
CC to the cleavage and inhibition of host MAVS (By similarity). Interacts
CC with host TICAM1; this interaction leads to the cleavage and inhibition
CC of host TICAM1 (By similarity). Interacts with host TANK-binding
CC kinase/TBK1; this interaction results in the inhibition of the
CC association between TBK1 and IRF3, which leads to the inhibition of
CC IRF3 activation (By similarity). Interacts with host RBM24 (By
CC similarity). 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:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2,
CC ECO:0000269|PubMed:10366511, ECO:0000269|PubMed:9568891}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with NS3 serine
CC protease; this interaction stabilizes the folding of NS3 serine
CC protease (PubMed:9568891, PubMed:10366511). NS3-NS4A interaction is
CC essential for NS3 activation and allows membrane anchorage of the
CC latter (PubMed:9568891). Interacts with non-structural protein 5A (via
CC N-terminus) (By similarity). Part of the replication complex composed
CC of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase
CC embedded in an ER-derived membranous web (By similarity). Part of the
CC viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A,
CC NS5A and the mature core protein (By similarity).
CC {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:10366511,
CC ECO:0000269|PubMed:9568891}.
CC -!- SUBUNIT: [Non-structural protein 5A]: Monomer (By similarity).
CC Homodimer; dimerization is required for RNA-binding (By similarity).
CC Interacts with the mature core protein (By similarity). Interacts (via
CC N-terminus) with non-structural protein 4A (By similarity). Interacts
CC with non-structural protein 4B (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 embedded in an ER-derived membranous web (By similarity).
CC Interacts with host GRB2 (PubMed:10318918). Interacts with host BIN1
CC (By similarity). Interacts with host PIK3R1 (PubMed:12186904).
CC Interacts with host SRCAP (By similarity). Interacts with host FKBP8
CC (By similarity). Interacts with host VAPB (By similarity). Interacts
CC with host EIF2AK2/PKR; this interaction leads to disruption of EIF2AK2
CC dimerization by NS5A and probably allows the virus to evade the innate
CC immune response (PubMed:9710605). Interacts (via N-terminus) with host
CC PACSIN2 (via N-terminus); this interaction attenuates protein kinase C
CC alpha-mediated phosphorylation of PACSIN2 by disrupting the interaction
CC between PACSIN2 and PRKCA (By similarity). Interacts (via N-terminus)
CC with host SRC kinase (via SH2 domain) (By similarity). Interacts with
CC most Src-family kinases (By similarity). Interacts with host IFI27 and
CC SKP2; promotes the ubiquitin-mediated proteasomal degradation of NS5A
CC (By similarity). Interacts with host GPS2 (By similarity). Interacts
CC with host TNFRSF21; this interaction allows the modulation by the virus
CC of JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent
CC manner (By similarity). Interacts (via N-terminus) with host CIDEB (via
CC N-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 (By similarity).
CC Interacts (via region D2) with host PPIA/CYPA; the interaction
CC stimulates RNA-binding ability of NS5A and is dependent on the
CC peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA. Interacts
CC with host TRIM14; this interaction induces the degradation of NS5A (By
CC similarity). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958,
CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:10318918,
CC ECO:0000269|PubMed:12186904, ECO:0000269|PubMed:9710605}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Homooligomer. Interacts with
CC non-structural protein 5A (By similarity). Interacts with host VAPB (By
CC similarity). Interacts with host PRK2/PKN2 (By similarity). Interacts
CC with host HNRNPA1 and SEPT6; these interactions facilitate the viral
CC replication (By similarity). Part of the replication complex composed
CC of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase
CC embedded in an ER-derived membranous web (By similarity).
CC {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.
CC -!- INTERACTION:
CC P26663; P52480: Pkm; Xeno; NbExp=3; IntAct=EBI-6857429, EBI-647785;
CC P26663; Q62245: Sos1; Xeno; NbExp=2; IntAct=EBI-6857429, EBI-1693;
CC PRO_0000037536; PRO_0000037537 [P26663]: -; NbExp=6; IntAct=EBI-6838571, EBI-6838576;
CC PRO_0000037536; P04637: TP53; Xeno; NbExp=9; IntAct=EBI-6838571, EBI-366083;
CC PRO_0000037540; PRO_0000037540 [P26663]: -; NbExp=2; IntAct=EBI-6874437, EBI-6874437;
CC PRO_0000037540; PRO_0000037548 [Q9WMX2]; Xeno; NbExp=5; IntAct=EBI-6874437, EBI-6863741;
CC -!- SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane
CC protein {ECO:0000255}. Host mitochondrion membrane
CC {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein
CC {ECO:0000255}. Note=The C-terminal transmembrane domain of the core
CC protein precursor contains an ER signal leading the nascent polyprotein
CC to the ER membrane.
CC -!- SUBCELLULAR LOCATION: [Mature core protein]: Virion
CC {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27958}. Host nucleus
CC {ECO:0000250|UniProtKB:P26662}. Host lipid droplet
CC {ECO:0000269|PubMed:17188392}. 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 (PubMed:17188392).
CC {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:17188392}.
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:P27958}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P27958}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P27958}. Host cell membrane
CC {ECO:0000250|UniProtKB:P27958}. 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:P27958}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P27958}. Host lipid droplet
CC {ECO:0000250|UniProtKB:Q9WMX2}. 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.
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:0000250|UniProtKB:P27958}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host
CC perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P26662}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27958}. Host nucleus
CC {ECO:0000250|UniProtKB:P26662}. Host lipid droplet
CC {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs
CC after processing by the NS3 protease (By similarity). Localizes at the
CC surface of lipid droplets (By similarity).
CC {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.
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 (PubMed:12660945). HVR1
CC is 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:P27958, ECO:0000269|PubMed:12660945}.
CC -!- DOMAIN: [Protease NS2]: The N-terminus of NS3 is required for the
CC catalytic activity of protease NS2 (PubMed:9261354, PubMed:11591719).
CC The minimal catalytic region includes the C-terminus of NS2 and the N-
CC terminus NS3 protease domain (active region NS2-3) (PubMed:11591719).
CC {ECO:0000269|PubMed:11591719, ECO:0000269|PubMed:9261354}.
CC -!- DOMAIN: [Serine protease/helicase NS3]: The N-terminal one-third of
CC serine protease/helicase NS3 contains the protease activity
CC (PubMed:9261354, PubMed:11591719). This region contains a zinc atom
CC that does not belong to the active site, but may play a structural
CC rather than a catalytic role (By similarity). This region is essential
CC for the activity of protease NS2, maybe by contributing to the folding
CC of the latter (By similarity). The NTPase/helicase activity is located
CC in the twothirds C-terminus of NS3, this domain contains the NTPase and
CC RNA-binding regions (PubMed:9614113). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000269|PubMed:11591719, ECO:0000269|PubMed:9261354,
CC ECO:0000269|PubMed:9614113}.
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 (Probable). The C-terminus of NS5A contains a variable
CC region called variable region 3 (V3) (By similarity). ISDR and V3 may
CC be involved in sensitivity and/or resistance to IFN-alpha therapy (By
CC similarity). The C-terminus contains a nuclear localization signal (By
CC similarity). The SH3-binding domain is involved in the interaction with
CC host BIN1, GRB2 and Src-family kinases (By similarity).
CC {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958,
CC ECO:0000305|PubMed:9710605}.
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 precursor is synthesized as a 23 kDa,
CC which is retained in the ER membrane through the hydrophobic signal
CC peptide (PubMed:8862403). Cleavage by the signal peptidase releases the
CC 21 kDa mature core protein (PubMed:8862403). The cleavage of the core
CC protein precursor occurs between aminoacids 176 and 188 but the exact
CC cleavage site is not known (PubMed:8862403). Some degraded forms of the
CC core protein appear as well during the course of infection
CC (PubMed:8862403). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A
CC and NS5B) are cleaved by the viral proteases (By similarity).
CC Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine
CC protease catalytic domain and regulated by the NS3 N-terminal domain
CC (PubMed:11591719). {ECO:0000250|UniProtKB:P27958,
CC ECO:0000269|PubMed:11591719, ECO:0000269|PubMed:8862403}.
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]: Phosphorylated on serines in a basal
CC form termed p56 (PubMed:11118372). p58 is a hyperphosphorylated form of
CC p56 (By similarity). p56 and p58 coexist in the cell in roughly
CC equivalent amounts (By similarity). Hyperphosphorylation is dependent
CC on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or
CC RPS6KB1 kinases may be responsible for NS5A phosphorylation
CC (PubMed:15016873, PubMed:16943283). {ECO:0000250|UniProtKB:P26662,
CC ECO:0000269|PubMed:11118372, ECO:0000269|PubMed:15016873,
CC ECO:0000269|PubMed:16943283}.
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:0000250|UniProtKB:P26662}.
CC -!- MISCELLANEOUS: Viral particle assembly takes place at the surface of
CC ER-derived membranes in close proximity to lipid droplets. NS2
CC associates with E1/E2 glycoproteins, NS3 and NS5A, which interacts with
CC the viral RNA and core protein to promote genome encapsidation. The
CC nucleocapsid buds at the ER membrane where E1/E2 glycoproteins are
CC anchored and afterward associate with nascent lipid droplet to acquire
CC APOE and APOC. Secretion of viral particles is probably regulated by
CC viroporin p7. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Non-structural protein 5A]: Cell culture adaptation of
CC the virus leads to mutations in NS5A, reducing its inhibitory effect on
CC replication. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Mature core protein]: Exerts viral interference on
CC hepatitis B virus when HCV and HBV coinfect the same cell, by
CC suppressing HBV gene expression, RNA encapsidation and budding.
CC {ECO:0000250|UniProtKB:P26662}.
CC -!- SIMILARITY: Belongs to the hepacivirus polyprotein family.
CC {ECO:0000305}.
CC -!- CAUTION: The core gene probably also codes for alternative reading
CC frame proteins (ARFPs). Many functions depicted for the core protein
CC might belong to the ARFPs. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_hcv";
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DR EMBL; M58335; AAA72945.1; -; Genomic_RNA.
DR PIR; A38465; GNWVTC.
DR PDB; 1A1Q; X-ray; 2.40 A; A/B/C=1027-1215.
DR PDB; 1BT7; NMR; -; A=1027-1206.
DR PDB; 1C2P; X-ray; 1.90 A; A/B=2422-2989.
DR PDB; 1CSJ; X-ray; 2.80 A; A/B=2420-2950.
DR PDB; 1CU1; X-ray; 2.50 A; A/B=1029-1657.
DR PDB; 1GX5; X-ray; 1.70 A; A=2420-2955.
DR PDB; 1GX6; X-ray; 1.85 A; A=2420-2950.
DR PDB; 1JXP; X-ray; 2.20 A; A/B=1027-1206, C/D=1678-1691.
DR PDB; 1NHU; X-ray; 2.00 A; A/B=2420-2989.
DR PDB; 1NHV; X-ray; 2.90 A; A/B=2420-2989.
DR PDB; 1NS3; X-ray; 2.80 A; A/B=1029-1206, C/D=1678-1689.
DR PDB; 1OS5; X-ray; 2.20 A; A=2420-2989.
DR PDB; 1QUV; X-ray; 2.50 A; A=2420-2989.
DR PDB; 2AWZ; X-ray; 2.15 A; A/B=2420-2989.
DR PDB; 2AX0; X-ray; 2.00 A; A/B=2420-2989.
DR PDB; 2AX1; X-ray; 2.10 A; A/B=2420-2989.
DR PDB; 2BRK; X-ray; 2.30 A; A=2420-2955.
DR PDB; 2BRL; X-ray; 2.40 A; A=2420-2955.
DR PDB; 2DXS; X-ray; 2.20 A; A/B=2420-2963.
DR PDB; 2GIQ; X-ray; 1.65 A; A/B=2421-2981.
DR PDB; 2GIR; X-ray; 1.90 A; A/B=2421-2981.
DR PDB; 2HAI; X-ray; 1.58 A; A=2420-2988.
DR PDB; 2HWH; X-ray; 2.30 A; A/B=2422-2989.
DR PDB; 2HWI; X-ray; 2.00 A; A/B=2422-2989.
DR PDB; 2I1R; X-ray; 2.20 A; A/B=2422-2989.
DR PDB; 2JC0; X-ray; 2.20 A; A/B=2420-2989.
DR PDB; 2JC1; X-ray; 2.00 A; A/B=2420-2989.
DR PDB; 2O5D; X-ray; 2.20 A; A/B=2422-2989.
DR PDB; 2WCX; X-ray; 2.00 A; A=2420-2955.
DR PDB; 2WHO; X-ray; 2.00 A; A/B=2420-2955.
DR PDB; 2WRM; X-ray; 1.95 A; A=2420-2955.
DR PDB; 2XWY; X-ray; 2.53 A; A=2420-2955.
DR PDB; 2ZKU; X-ray; 1.95 A; A/B/C/D=2420-2989.
DR PDB; 3BR9; X-ray; 2.30 A; A/B=2420-2989.
DR PDB; 3BSA; X-ray; 2.30 A; A/B=2420-2989.
DR PDB; 3BSC; X-ray; 2.65 A; A/B=2420-2989.
DR PDB; 3CDE; X-ray; 2.10 A; A/B=2420-2989.
DR PDB; 3CIZ; X-ray; 1.87 A; A/B=2421-2989.
DR PDB; 3CJ0; X-ray; 1.90 A; A/B=2421-2989.
DR PDB; 3CJ2; X-ray; 1.75 A; A/B=2421-2989.
DR PDB; 3CJ3; X-ray; 1.87 A; A/B=2421-2989.
DR PDB; 3CJ4; X-ray; 2.07 A; A/B=2421-2989.
DR PDB; 3CJ5; X-ray; 1.92 A; A/B=2421-2989.
DR PDB; 3CO9; X-ray; 2.10 A; A/B=2420-2989.
DR PDB; 3CVK; X-ray; 2.31 A; A/B=2420-2989.
DR PDB; 3CWJ; X-ray; 2.40 A; A/B=2420-2989.
DR PDB; 3D28; X-ray; 2.30 A; A/B=2420-2989.
DR PDB; 3D5M; X-ray; 2.20 A; A/B=2420-2989.
DR PDB; 3E51; X-ray; 1.90 A; A/B=2420-2989.
DR PDB; 3FQK; X-ray; 2.20 A; A/B=2421-2989.
DR PDB; 3FRZ; X-ray; 1.86 A; A=2420-2989.
DR PDB; 3G86; X-ray; 2.20 A; A/B=2421-2989.
DR PDB; 3GYN; X-ray; 2.15 A; A/B=2420-2989.
DR PDB; 3H2L; X-ray; 1.90 A; A/B=2420-2989.
DR PDB; 3H59; X-ray; 2.10 A; A/B=2421-2989.
DR PDB; 3H5S; X-ray; 2.00 A; A/B=2421-2989.
DR PDB; 3H5U; X-ray; 1.95 A; A/B=2421-2989.
DR PDB; 3H98; X-ray; 1.90 A; A/B=2421-2989.
DR PDB; 3IGV; X-ray; 2.60 A; A/B=2420-2989.
DR PDB; 3MF5; X-ray; 2.00 A; A/B=2421-2989.
DR PDB; 3RVB; X-ray; 2.20 A; A=1186-1657.
DR PDB; 3UA7; X-ray; 1.50 A; E/F=2321-2331.
DR PDB; 3UDL; X-ray; 2.17 A; A/B/C/D=2420-2989.
DR PDB; 3VQS; X-ray; 1.90 A; A/B/C/D=2420-2989.
DR PDB; 4A92; X-ray; 2.73 A; A/B=1029-1657, A/B=1678-1690.
DR PDB; 4B6E; X-ray; 2.46 A; A/B=1029-1657.
DR PDB; 4B6F; X-ray; 2.89 A; A/B=1029-1657.
DR PDB; 4B71; X-ray; 2.50 A; A/B=1029-1657.
DR PDB; 4B73; X-ray; 2.50 A; A/B=1029-1657.
DR PDB; 4B74; X-ray; 2.18 A; A/B=1029-1657.
DR PDB; 4B75; X-ray; 2.53 A; A/B=1029-1655.
DR PDB; 4B76; X-ray; 2.14 A; A/B=1029-1657.
DR PDB; 4DGV; X-ray; 1.80 A; A=412-423.
DR PDB; 4DGY; X-ray; 1.80 A; A=412-423.
DR PDB; 4EO6; X-ray; 1.79 A; A/B=2422-2989.
DR PDB; 4EO8; X-ray; 1.80 A; A/B=2422-2989.
DR PDB; 4IH5; X-ray; 1.90 A; A/B=2421-2989.
DR PDB; 4IH6; X-ray; 2.20 A; A/B=2421-2989.
DR PDB; 4IH7; X-ray; 2.30 A; A/B=2421-2989.
DR PDB; 4K8B; X-ray; 2.80 A; C/D=1678-1689.
DR PDB; 4KAI; X-ray; 2.30 A; A/B=2420-2989.
DR PDB; 4KB7; X-ray; 1.85 A; A/B=2420-2989.
DR PDB; 4KBI; X-ray; 2.06 A; A/B=2420-2989.
DR PDB; 4KE5; X-ray; 2.11 A; A/B=2420-2989.
DR PDB; 4MIA; X-ray; 2.80 A; A/B=2421-2989.
DR PDB; 4MIB; X-ray; 2.30 A; A/B=2421-2989.
DR PDB; 4MK7; X-ray; 2.80 A; A/B=2421-2989.
DR PDB; 4MK8; X-ray; 2.09 A; A/B=2421-2989.
DR PDB; 4MK9; X-ray; 2.05 A; A/B=2421-2989.
DR PDB; 4MKA; X-ray; 2.05 A; A/B=2421-2989.
DR PDB; 4MKB; X-ray; 1.90 A; A/B=2421-2989.
DR PDB; 4TN2; X-ray; 2.70 A; A=2422-2989.
DR PDB; 4WXP; X-ray; 2.08 A; A=1206-1656.
DR PDB; 5FPS; X-ray; 2.68 A; A/B=1029-1657.
DR PDB; 5FPT; X-ray; 2.72 A; A/B=1029-1657.
DR PDB; 5FPY; X-ray; 2.52 A; A/B=1029-1657.
DR PDB; 5KZP; X-ray; 2.26 A; A/B/C/D=412-423.
DR PDB; 5W2E; X-ray; 2.80 A; A/B=2422-2989.
DR PDB; 6MVP; X-ray; 2.00 A; A/B=2420-2989.
DR PDB; 6W4G; X-ray; 1.95 A; A/B=2421-2981.
DR PDB; 8OHM; X-ray; 2.30 A; A=1216-1650.
DR PDBsum; 1A1Q; -.
DR PDBsum; 1BT7; -.
DR PDBsum; 1C2P; -.
DR PDBsum; 1CSJ; -.
DR PDBsum; 1CU1; -.
DR PDBsum; 1GX5; -.
DR PDBsum; 1GX6; -.
DR PDBsum; 1JXP; -.
DR PDBsum; 1NHU; -.
DR PDBsum; 1NHV; -.
DR PDBsum; 1NS3; -.
DR PDBsum; 1OS5; -.
DR PDBsum; 1QUV; -.
DR PDBsum; 2AWZ; -.
DR PDBsum; 2AX0; -.
DR PDBsum; 2AX1; -.
DR PDBsum; 2BRK; -.
DR PDBsum; 2BRL; -.
DR PDBsum; 2DXS; -.
DR PDBsum; 2GIQ; -.
DR PDBsum; 2GIR; -.
DR PDBsum; 2HAI; -.
DR PDBsum; 2HWH; -.
DR PDBsum; 2HWI; -.
DR PDBsum; 2I1R; -.
DR PDBsum; 2JC0; -.
DR PDBsum; 2JC1; -.
DR PDBsum; 2O5D; -.
DR PDBsum; 2WCX; -.
DR PDBsum; 2WHO; -.
DR PDBsum; 2WRM; -.
DR PDBsum; 2XWY; -.
DR PDBsum; 2ZKU; -.
DR PDBsum; 3BR9; -.
DR PDBsum; 3BSA; -.
DR PDBsum; 3BSC; -.
DR PDBsum; 3CDE; -.
DR PDBsum; 3CIZ; -.
DR PDBsum; 3CJ0; -.
DR PDBsum; 3CJ2; -.
DR PDBsum; 3CJ3; -.
DR PDBsum; 3CJ4; -.
DR PDBsum; 3CJ5; -.
DR PDBsum; 3CO9; -.
DR PDBsum; 3CVK; -.
DR PDBsum; 3CWJ; -.
DR PDBsum; 3D28; -.
DR PDBsum; 3D5M; -.
DR PDBsum; 3E51; -.
DR PDBsum; 3FQK; -.
DR PDBsum; 3FRZ; -.
DR PDBsum; 3G86; -.
DR PDBsum; 3GYN; -.
DR PDBsum; 3H2L; -.
DR PDBsum; 3H59; -.
DR PDBsum; 3H5S; -.
DR PDBsum; 3H5U; -.
DR PDBsum; 3H98; -.
DR PDBsum; 3IGV; -.
DR PDBsum; 3MF5; -.
DR PDBsum; 3RVB; -.
DR PDBsum; 3UA7; -.
DR PDBsum; 3UDL; -.
DR PDBsum; 3VQS; -.
DR PDBsum; 4A92; -.
DR PDBsum; 4B6E; -.
DR PDBsum; 4B6F; -.
DR PDBsum; 4B71; -.
DR PDBsum; 4B73; -.
DR PDBsum; 4B74; -.
DR PDBsum; 4B75; -.
DR PDBsum; 4B76; -.
DR PDBsum; 4DGV; -.
DR PDBsum; 4DGY; -.
DR PDBsum; 4EO6; -.
DR PDBsum; 4EO8; -.
DR PDBsum; 4IH5; -.
DR PDBsum; 4IH6; -.
DR PDBsum; 4IH7; -.
DR PDBsum; 4K8B; -.
DR PDBsum; 4KAI; -.
DR PDBsum; 4KB7; -.
DR PDBsum; 4KBI; -.
DR PDBsum; 4KE5; -.
DR PDBsum; 4MIA; -.
DR PDBsum; 4MIB; -.
DR PDBsum; 4MK7; -.
DR PDBsum; 4MK8; -.
DR PDBsum; 4MK9; -.
DR PDBsum; 4MKA; -.
DR PDBsum; 4MKB; -.
DR PDBsum; 4TN2; -.
DR PDBsum; 4WXP; -.
DR PDBsum; 5FPS; -.
DR PDBsum; 5FPT; -.
DR PDBsum; 5FPY; -.
DR PDBsum; 5KZP; -.
DR PDBsum; 5W2E; -.
DR PDBsum; 6MVP; -.
DR PDBsum; 6W4G; -.
DR PDBsum; 8OHM; -.
DR BMRB; P26663; -.
DR SASBDB; P26663; -.
DR SMR; P26663; -.
DR IntAct; P26663; 6.
DR MINT; P26663; -.
DR BindingDB; P26663; -.
DR ChEMBL; CHEMBL6040; -.
DR DrugBank; DB08706; (2S)-({(5Z)-5-[(5-Ethyl-2-furyl)methylene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl}amino)(4-fluorophenyl)acetic acid.
DR DrugBank; DB03605; (2s)-2-[(2,4-Dichloro-Benzoyl)-(3-Trifluoromethyl-Benzyl)-Amino]-3-Phenyl-Propionic Acid.
DR DrugBank; DB02331; (2s)-2-[(5-Benzofuran-2-Yl-Thiophen-2-Ylmethyl)-(2,4-Dichloro-Benzoyl)-Amino]-3-Phenyl-Propionic Acid.
DR DrugBank; DB07199; (2S,4S,5R)-1-(4-TERT-BUTYLBENZOYL)-2-ISOBUTYL-5-(1,3-THIAZOL-2-YL)PYRROLIDINE-2,4-DICARBOXYLIC ACID.
DR DrugBank; DB07200; (2S,4S,5R)-2-ISOBUTYL-5-(2-THIENYL)-1-[4-(TRIFLUOROMETHYL)BENZOYL]PYRROLIDINE-2,4-DICARBOXYLIC ACID.
DR DrugBank; DB07414; (5S)-1-benzyl-3-(1,1-dioxido-1,2-benzisothiazol-3-yl)-4-hydroxy-5-(1-methylethyl)-1,5-dihydro-2H-pyrrol-2-one.
DR DrugBank; DB08710; (5Z)-5-[(5-ethylfuran-2-yl)methylidene]-2-[[(S)-(4-fluorophenyl)-(2H-tetrazol-5-yl)methyl]amino]-1,3-thiazol-4-one.
DR DrugBank; DB08390; (6S)-6-CYCLOPENTYL-6-[2-(3-FLUORO-4-ISOPROPOXYPHENYL)ETHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE.
DR DrugBank; DB08278; 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone.
DR DrugBank; DB08701; 2-(3-BROMOPHENYL)-6-[(2-HYDROXYETHYL)AMINO]-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONE.
DR DrugBank; DB04298; 3-(4-Amino-2-Tert-Butyl-5-Methyl-Phenylsulfanyl)-6-Cyclopentyl-4-Hydroxy-6-[2-(4-Hydroxy-Phenyl)-Ethyl]-5,6-Dihydro-Pyran-2-One.
DR DrugBank; DB07570; 3-CYCLOHEXYL-1-(2-MORPHOLIN-4-YL-2-OXOETHYL)-2-PHENYL-1H-INDOLE-6-CARBOXYLIC ACID.
DR DrugBank; DB08279; 3-{ISOPROPYL[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]AMINO}-5-PHENYLTHIOPHENE-2-CARBOXYLIC ACID.
DR DrugBank; DB08581; 4-[(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)amino]-4-oxobutanoic acid.
DR DrugBank; DB08578; 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoic acid.
DR DrugBank; DB08580; 4-bromo-2-{[(2R)-2-(2-chlorobenzyl)pyrrolidin-1-yl]carbonyl}aniline.
DR DrugBank; DB08579; 4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}aniline.
DR DrugBank; DB08481; 4-Methyl-N-[5-(5-methyl-furan-2-ylmethylene)-4-oxo-thiazolidin-2-ylidene]-benzenesulfonamide.
DR DrugBank; DB06974; 5-hydroxy-4-(7-methoxy-1,1-dioxido-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one.
DR DrugBank; DB07169; 5R-(3,4-DICHLOROPHENYLMETHYL)-3-(2-THIOPHENESULFONYLAMINO)-4-OXO-2-THIONOTHIAZOLIDINE.
DR DrugBank; DB11586; Asunaprevir.
DR DrugBank; DB04137; Guanosine-5'-Triphosphate.
DR DrugBank; DB08582; N-(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)-4-morpholin-4-yl-4-oxobutanamide.
DR DrugBank; DB08031; N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE.
DR DrugBank; DB07062; N-{3-[4-Hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydropyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide.
DR DrugBank; DB07238; Nesbuvir.
DR DrugBank; DB04005; Uridine 5'-triphosphate.
DR DrugCentral; P26663; -.
DR MEROPS; S29.001; -.
DR iPTMnet; P26663; -.
DR ABCD; P26663; 5 sequenced antibodies.
DR euHCVdb; M58335; -.
DR BRENDA; 3.4.21.98; 17002.
DR EvolutionaryTrace; P26663; -.
DR Proteomes; UP000007413; Segment.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044186; C:host cell lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO: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:0039563; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039527; P:disruption by virus of host TRAF-mediated signal transduction; IEA:UniProtKB-KW.
DR GO; GO: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:perturbation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; 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 GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
DR CDD; cd17931; DEXHc_viral_Ns3; 1.
DR CDD; cd20903; HCV_p7; 1.
DR CDD; cd23202; Hepacivirus_RdRp; 1.
DR CDD; cd18806; SF2_C_viral; 1.
DR Gene3D; 2.40.10.120; -; 1.
DR Gene3D; 3.30.70.270; -; 2.
DR Gene3D; 6.10.250.1610; -; 1.
DR Gene3D; 6.10.250.1750; -; 1.
DR Gene3D; 6.10.250.2920; -; 1.
DR Gene3D; 2.20.25.210; Hepatitis C NS5A, domain 1B; 1.
DR Gene3D; 3.30.160.890; Hepatitis C virus envelope glycoprotein E1, chain C; 1.
DR Gene3D; 2.30.30.710; Hepatitis C virus non-structural protein NS2, C-terminal domain; 1.
DR Gene3D; 1.20.1280.150; Hepatitis C virus non-structural protein NS2, N-terminal domain; 1.
DR Gene3D; 2.20.25.220; Hepatitis C virus NS5A, 1B domain; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR Gene3D; 1.10.820.10; RNA Helicase Chain A , domain 3; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR011492; Flavi_DEAD.
DR InterPro; IPR002521; HCV_Core_C.
DR InterPro; IPR044896; HCV_core_chain_A.
DR InterPro; IPR002522; HCV_core_N.
DR InterPro; IPR002519; HCV_Env.
DR InterPro; IPR002531; HCV_NS1.
DR InterPro; IPR002518; HCV_NS2.
DR InterPro; IPR042205; HCV_NS2_C.
DR InterPro; IPR042209; HCV_NS2_N.
DR InterPro; IPR000745; HCV_NS4a.
DR InterPro; IPR001490; HCV_NS4b.
DR InterPro; IPR002868; HCV_NS5a.
DR InterPro; IPR013192; HCV_NS5A_1a.
DR InterPro; IPR013193; HCV_NS5a_1B_dom.
DR InterPro; IPR038568; HCV_NS5A_1B_sf.
DR InterPro; IPR024350; HCV_NS5a_C.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR004109; HepC_NS3_protease.
DR InterPro; IPR038170; NS5A_1a_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002166; RNA_pol_HCV.
DR Pfam; PF07652; Flavi_DEAD; 1.
DR Pfam; PF01543; HCV_capsid; 1.
DR Pfam; PF01542; HCV_core; 1.
DR Pfam; PF01539; HCV_env; 1.
DR Pfam; PF01560; HCV_NS1; 1.
DR Pfam; PF01538; HCV_NS2; 1.
DR Pfam; PF01006; HCV_NS4a; 1.
DR Pfam; PF01001; HCV_NS4b; 1.
DR Pfam; PF01506; HCV_NS5a; 1.
DR Pfam; PF08300; HCV_NS5a_1a; 1.
DR Pfam; PF08301; HCV_NS5a_1b; 1.
DR Pfam; PF12941; HCV_NS5a_C; 1.
DR Pfam; PF02907; Peptidase_S29; 1.
DR Pfam; PF00998; RdRP_3; 1.
DR SMART; SM00487; DEXDc; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS51693; HCV_NS2_PRO; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51822; HV_PV_NS3_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activation of host autophagy by virus;
KW Apoptosis; ATP-binding; Capsid protein;
KW Clathrin-mediated endocytosis of virus by host; Direct protein sequencing;
KW Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane;
KW G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein;
KW Helicase; Host cell membrane; Host cytoplasm; Host endoplasmic reticulum;
KW Host lipid droplet; Host membrane; Host mitochondrion; Host nucleus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host STAT1 by virus; Inhibition of host TRAFs by virus;
KW Interferon antiviral system evasion; Ion channel; Ion transport;
KW Isopeptide bond; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Modulation of host cell cycle by virus; Multifunctional enzyme;
KW Nucleotide-binding; Nucleotidyltransferase; Oncogene; Palmitate;
KW Phosphoprotein; Protease; Ribonucleoprotein; RNA-binding;
KW RNA-directed RNA polymerase; Serine protease; SH3-binding; 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_0000450852"
FT CHAIN 2..191
FT /note="Core protein precursor"
FT /id="PRO_0000037529"
FT CHAIN 2..177
FT /note="Mature core protein"
FT /id="PRO_0000037530"
FT PROPEP 178..191
FT /note="ER anchor for the core protein, removed in mature
FT form by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT /id="PRO_0000037531"
FT CHAIN 192..383
FT /note="Envelope glycoprotein E1"
FT /id="PRO_0000037532"
FT CHAIN 384..746
FT /note="Envelope glycoprotein E2"
FT /id="PRO_0000037533"
FT CHAIN 747..809
FT /note="Viroporin p7"
FT /id="PRO_0000037534"
FT CHAIN 810..1026
FT /note="Protease NS2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT /id="PRO_0000037535"
FT CHAIN 1027..1657
FT /note="Serine protease/helicase NS3"
FT /id="PRO_0000037536"
FT CHAIN 1658..1711
FT /note="Non-structural protein 4A"
FT /id="PRO_0000037537"
FT CHAIN 1712..1972
FT /note="Non-structural protein 4B"
FT /id="PRO_0000037538"
FT CHAIN 1973..2419
FT /note="Non-structural protein 5A"
FT /id="PRO_0000037539"
FT CHAIN 2420..3010
FT /note="RNA-directed RNA polymerase"
FT /id="PRO_0000037540"
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..2003
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT TOPO_DOM 2004..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:0000305|PubMed:8189501"
FT REGION 2..59
FT /note="Interaction with DDX3X"
FT /evidence="ECO:0000250|UniProtKB:Q5EG65"
FT REGION 2..58
FT /note="Interaction with EIF2AK2/PKR"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT REGION 2..23
FT /note="Interaction with STAT1"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT REGION 112..152
FT /note="Important for endoplasmic reticulum and
FT mitochondrial localization"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT REGION 122..173
FT /note="Interaction with APOA2"
FT /evidence="ECO:0000250|UniProtKB:P29846"
FT REGION 164..167
FT /note="Important for lipid droplets localization"
FT /evidence="ECO: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..494
FT /note="CD81-binding 1"
FT /evidence="ECO:0000269|PubMed:12660945"
FT REGION 544..552
FT /note="CD81-binding 2"
FT /evidence="ECO:0000269|PubMed:12660945"
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:0000269|PubMed:11591719"
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:0000269|PubMed:9614113"
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:0000250|UniProtKB:P26662"
FT REGION 2135..2139
FT /note="Interaction with non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT REGION 2189..2441
FT /note="Interaction with host SKP2"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT REGION 2210..2275
FT /note="EIF2AK2/PKR-binding"
FT /evidence="ECO:0000269|PubMed:9710605"
FT REGION 2210..2249
FT /note="ISDR"
FT /evidence="ECO:0000269|PubMed:9710605"
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..2407
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:0000250|UniProtKB:P26662"
FT COMPBIAS 47..69
FT /note="Basic and acidic 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 ACT_SITE 1083
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT ECO:0000269|PubMed:8861916"
FT ACT_SITE 1107
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT ECO:0000269|PubMed:8861916"
FT ACT_SITE 1165
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01166,
FT ECO:0000269|PubMed:8861916, ECO:0000269|PubMed:9568891"
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:10366511, ECO:0000269|PubMed:8861916,
FT ECO:0000269|PubMed:9568891"
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:10366511, ECO:0000269|PubMed:8861916,
FT ECO:0000269|PubMed:9568891"
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:10366511, ECO:0000269|PubMed:8861916"
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:10366511, ECO:0000269|PubMed:8861916"
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:0000305|PubMed:10557268,
FT ECO:0000305|PubMed:11884572"
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:0000305|PubMed:10557268,
FT ECO:0000305|PubMed:11884572"
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:0000305|PubMed:10557268,
FT ECO:0000305|PubMed:11884572"
FT SITE 177..178
FT /note="Cleavage; by host signal peptide peptidase"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT SITE 191..192
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT SITE 383..384
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P26662"
FT SITE 746..747
FT /note="Cleavage; by host signal peptidase"
FT /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:11118372"
FT MOD_RES 2197
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT MOD_RES 2201
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000250|UniProtKB:Q9WMX2"
FT MOD_RES 2204
FT /note="Phosphoserine; by host; in p58"
FT /evidence="ECO:0000250|UniProtKB:Q9WMX2"
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:0000250|UniProtKB:P26662"
FT MOD_RES 2461
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P26662"
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:0000269|PubMed:8862403"
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 250
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:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
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 532
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000250|UniProtKB:P27958"
FT CARBOHYD 540
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 MUTAGEN 2194
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:11118372"
FT MUTAGEN 2322
FT /note="P->A: Complete loss of binding to GRB2."
FT /evidence="ECO:0000269|PubMed:10318918"
FT MUTAGEN 2323
FT /note="P->A: Complete loss of binding to GRB2."
FT /evidence="ECO:0000269|PubMed:10318918"
FT MUTAGEN 2326
FT /note="P->A: Complete loss of binding to GRB2."
FT /evidence="ECO:0000269|PubMed:10318918"
FT MUTAGEN 2639
FT /note="D->C,G,N: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2644
FT /note="D->G,N: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2702
FT /note="G->D,L,R: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2705
FT /note="T->V: Almost complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2706
FT /note="T->C: Almost complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2706
FT /note="T->K: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2710
FT /note="N->K: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2736
FT /note="G->A,C: Almost complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2737
FT /note="D->E,H,N: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT MUTAGEN 2738
FT /note="D->H: Complete loss of RdRp activity."
FT /evidence="ECO:0000269|PubMed:9343198"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:4DGY"
FT STRAND 419..422
FT /evidence="ECO:0007829|PDB:4DGY"
FT STRAND 1017..1023
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1031..1035
FT /evidence="ECO:0007829|PDB:4B76"
FT HELIX 1039..1048
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1057..1063
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1068..1074
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1077..1080
FT /evidence="ECO:0007829|PDB:4B76"
FT HELIX 1082..1085
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1090..1092
FT /evidence="ECO:0007829|PDB:1JXP"
FT STRAND 1095..1097
FT /evidence="ECO:0007829|PDB:1JXP"
FT STRAND 1100..1103
FT /evidence="ECO:0007829|PDB:4B76"
FT TURN 1104..1107
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1108..1112
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1128..1133
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1135..1137
FT /evidence="ECO:0007829|PDB:1BT7"
FT STRAND 1139..1144
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1146..1157
FT /evidence="ECO:0007829|PDB:4B76"
FT HELIX 1158..1161
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1168..1170
FT /evidence="ECO:0007829|PDB:4B76"
FT TURN 1172..1174
FT /evidence="ECO:0007829|PDB:1JXP"
FT STRAND 1176..1186
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1189..1197
FT /evidence="ECO:0007829|PDB:4B76"
FT HELIX 1198..1206
FT /evidence="ECO:0007829|PDB:4B76"
FT STRAND 1224..1229
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1232..1235
FT /evidence="ECO:0007829|PDB:1CU1"
FT TURN 1236..1238
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1239..1246
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1251..1256
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1258..1272
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1277..1279
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1290..1295
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1296..1301
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1307..1309
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1311..1315
FT /evidence="ECO:0007829|PDB:4WXP"
FT TURN 1316..1319
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1323..1335
FT /evidence="ECO:0007829|PDB:4WXP"
FT TURN 1336..1340
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1342..1350
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1362..1366
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1371..1375
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1378..1380
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1382..1384
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1386..1393
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1397..1409
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1414..1417
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1419..1421
FT /evidence="ECO:0007829|PDB:8OHM"
FT HELIX 1423..1425
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1428..1430
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1432..1436
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1438..1441
FT /evidence="ECO:0007829|PDB:4WXP"
FT TURN 1442..1444
FT /evidence="ECO:0007829|PDB:8OHM"
FT STRAND 1448..1453
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1456..1463
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1467..1469
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1471..1478
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1481..1488
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1493..1495
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1497..1503
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1509..1511
FT /evidence="ECO:0007829|PDB:4B76"
FT HELIX 1514..1526
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1532..1544
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1555..1563
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1570..1579
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1584..1596
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1606..1611
FT /evidence="ECO:0007829|PDB:4WXP"
FT TURN 1612..1614
FT /evidence="ECO:0007829|PDB:4WXP"
FT HELIX 1615..1617
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1625..1629
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1635..1637
FT /evidence="ECO:0007829|PDB:8OHM"
FT HELIX 1640..1650
FT /evidence="ECO:0007829|PDB:4WXP"
FT TURN 1653..1655
FT /evidence="ECO:0007829|PDB:4WXP"
FT STRAND 1680..1688
FT /evidence="ECO:0007829|PDB:1JXP"
FT STRAND 2421..2425
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2446..2449
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2453..2455
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2456..2458
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2461..2463
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2464..2471
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2481..2494
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2504..2509
FT /evidence="ECO:0007829|PDB:2GIQ"
FT TURN 2519..2521
FT /evidence="ECO:0007829|PDB:2WRM"
FT HELIX 2524..2528
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2532..2547
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2549..2551
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2555..2559
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2563..2565
FT /evidence="ECO:0007829|PDB:2GIQ"
FT TURN 2568..2571
FT /evidence="ECO:0007829|PDB:1GX5"
FT STRAND 2578..2581
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2584..2606
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2607..2609
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2611..2613
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2616..2629
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2630..2638
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2643..2646
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2649..2659
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2666..2678
FT /evidence="ECO:0007829|PDB:2GIQ"
FT TURN 2679..2681
FT /evidence="ECO:0007829|PDB:1GX6"
FT STRAND 2683..2686
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2688..2690
FT /evidence="ECO:0007829|PDB:1CSJ"
FT STRAND 2692..2696
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2701..2703
FT /evidence="ECO:0007829|PDB:2HWI"
FT HELIX 2706..2724
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2728..2735
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2738..2744
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2748..2764
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2769..2771
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2776..2778
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2779..2781
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2787..2793
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2795..2797
FT /evidence="ECO:0007829|PDB:3CVK"
FT STRAND 2799..2804
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2808..2819
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2826..2833
FT /evidence="ECO:0007829|PDB:2GIQ"
FT TURN 2834..2836
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2838..2842
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2844..2854
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2858..2860
FT /evidence="ECO:0007829|PDB:3BSA"
FT STRAND 2862..2866
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2869..2873
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2875..2877
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2878..2886
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2888..2891
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2898..2911
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2916..2933
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2935..2944
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2946..2948
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2949..2951
FT /evidence="ECO:0007829|PDB:2GIQ"
FT HELIX 2959..2962
FT /evidence="ECO:0007829|PDB:2GIQ"
FT TURN 2967..2970
FT /evidence="ECO:0007829|PDB:2GIQ"
FT STRAND 2976..2978
FT /evidence="ECO:0007829|PDB:4KE5"
FT STRAND 2980..2982
FT /evidence="ECO:0007829|PDB:4EO6"
SQ SEQUENCE 3010 AA; 327194 MW; F8422D5ECCFDFD9C CRC64;
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRAPR KTSERSQPRG
RRQPIPKARR PEGRTWAQPG YPWPLYGNEG LGWAGWLLSP RGSRPSWGPT DPRRRSRNLG
KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA
LLSCLTTPAS AYEVHNVSGI YHVTNDCSNA SIVYEAADLI MHTPGCVPCV REGNSSRCWV
ALTPTLAARN VTIPTTTIRR HVDLLVGAAA FCSAMYVGDL CGSVFLVSQL FTFSPRRHVT
LQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG AHWGVLAGLA
YYSMAGNWAK VLIVMLLFAG VDGDTHVTGG AQAKTTNRLV SMFASGPSQK IQLINTNGSW
HINRTALNCN DSLQTGFLAA LFYTHSFNSS GCPERMAQCR TIDKFDQGWG PITYAESSRS
DQRPYCWHYP PPQCTIVPAS EVCGPVYCFT PSPVVVGTTD RFGVPTYRWG ENETDVLLLN
NTRPPQGNWF GCTWMNSTGF TKTCGGPPCN IGGVGNNTLT CPTDCFRKHP EATYTKCGSG
PWLTPRCMVD YPYRLWHYPC TVNFTIFKVR MYVGGVEHRL NAACNWTRGE RCDLEDRDRP
ELSPLLLSTT EWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGIGSAVV SFAIKWEYVL
LLFLLLADAR VCACLWMMLL IAQAEAALEN LVVLNSASVA GAHGILSFLV FFCAAWYIKG
RLVPGATYAL YGVWPLLLLL LALPPRAYAM DREMAASCGG AVFVGLVLLT LSPYYKVFLA
RLIWWLQYFT TRAEADLHVW IPPLNARGGR DAIILLMCAV HPELIFDITK LLIAILGPLM
VLQAGITRVP YFVRAQGLIH ACMLVRKVAG GHYVQMAFMK LGALTGTYIY NHLTPLRDWP
RAGLRDLAVA VEPVVFSDME TKIITWGADT AACGDIILGL PVSARRGKEI LLGPADSLEG
RGLRLLAPIT AYSQQTRGLL GCIITSLTGR DKNQVEGEVQ VVSTATQSFL ATCVNGVCWT
VYHGAGSKTL AAPKGPITQM YTNVDQDLVG WPKPPGARSL TPCTCGSSDL YLVTRHADVI
PVRRRGDSRG SLLSPRPVSY LKGSSGGPLL CPFGHAVGIF RAAVCTRGVA KAVDFVPVES
METTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK VLVLNPSVAA
TLGFGAYMSK AHGIDPNIRT GVRTITTGAP VTYSTYGKFL ADGGCSGGAY DIIICDECHS
TDSTTILGIG TVLDQAETAG ARLVVLATAT PPGSVTVPHP NIEEVALSNT GEIPFYGKAI
PIEAIRGGRH LIFCHSKKKC DELAAKLSGL GINAVAYYRG LDVSVIPTIG DVVVVATDAL
MTGYTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRRGIYR
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV CQDHLEFWES
VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP PPSWDQMWKC LIRLKPTLHG
PTPLLYRLGA VQNEVTLTHP ITKYIMACMS ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV
VIVGRIILSG RPAIVPDREL LYQEFDEMEE CASHLPYIEQ GMQLAEQFKQ KALGLLQTAT
KQAEAAAPVV ESKWRALETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP
LTTQSTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD ILAGYGAGVA
GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA ILRRHVGPGE GAVQWMNRLI
AFASRGNHVS PTHYVPESDA AARVTQILSS LTITQLLKRL HQWINEDCST PCSGSWLRDV
WDWICTVLTD FKTWLQSKLL PQLPGVPFFS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK
NGSMRIVGPK TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH
YVTGMTTDNV KCPCQVPAPE FFSEVDGVRL HRYAPACRPL LREEVTFQVG LNQYLVGSQL
PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS SSASQLSAPS LKATCTTHHV
SPDADLIEAN LLWRQEMGGN ITRVESENKV VVLDSFDPLR AEEDEREVSV PAEILRKSKK
FPAAMPIWAR PDYNPPLLES WKDPDYVPPV VHGCPLPPIK APPIPPPRRK RTVVLTESSV
SSALAELATK TFGSSESSAV DSGTATALPD QASDDGDKGS DVESYSSMPP LEGEPGDPDL
SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEESKL PINALSNSLL RHHNMVYATT
SRSAGLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK LLSVEEACKL TPPHSAKSKF
GYGAKDVRNL SSKAVNHIHS VWKDLLEDTV TPIDTTIMAK NEVFCVQPEK GGRKPARLIV
FPDLGVRVCE KMALYDVVST LPQVVMGSSY GFQYSPGQRV EFLVNTWKSK KNPMGFSYDT
RCFDSTVTEN DIRVEESIYQ CCDLAPEARQ AIKSLTERLY IGGPLTNSKG QNCGYRRCRA
SGVLTTSCGN TLTCYLKASA ACRAAKLQDC TMLVNGDDLV VICESAGTQE DAASLRVFTE
AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV YYLTRDPTTP LARAAWETAR
HTPVNSWLGN IIMYAPTLWA RMILMTHFFS ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ
IIERLHGLSA FSLHSYSPGE INRVASCLRK LGVPPLRVWR HRARSVRARL LSQGGRAATC
GKYLFNWAVK TKLKLTPIPA ASRLDLSGWF VAGYSGGDIY HSLSRARPRW FMLCLLLLSV
GVGIYLLPNR
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