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P26664

- POLG_HCV1

UniProt

P26664 - POLG_HCV1

Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1a (isolate 1) (HCV)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 157 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) By similarity.By similarity
    E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection.
    P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity By similarity.By similarity
    Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation.
    NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS By similarity.By similarity
    NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex By similarity.By similarity
    NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication By similarity.By similarity
    NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication.By similarity

    Catalytic activityi

    Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
    Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
    NTP + H2O = NDP + phosphate.
    ATP + H2O = ADP + phosphate.

    Cofactori

    Binds 1 zinc ion per NS3 protease domain.By similarity
    Binds 1 zinc ion per NS5A N-terminal domain.By similarity

    Enzyme regulationi

    Activity of auto-protease NS2-3 is dependent on zinc ions and completely inhibited by EDTA. Serine protease NS3 is also activated by zinc ions By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei177 – 1782Cleavage; by host signal peptidaseBy similarity
    Sitei191 – 1922Cleavage; by host signal peptidaseSequence Analysis
    Sitei383 – 3842Cleavage; by host signal peptidaseSequence Analysis
    Sitei746 – 7472Cleavage; by host signal peptidaseBy similarity
    Sitei809 – 8102Cleavage; by host signal peptidaseBy similarity
    Active sitei952 – 9521For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Active sitei972 – 9721For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Active sitei993 – 9931For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Sitei1026 – 10272Cleavage; by protease NS2-3PROSITE-ProRule annotation
    Active sitei1083 – 10831Charge relay system; for serine protease NS3 activityBy similarity
    Active sitei1107 – 11071Charge relay system; for serine protease NS3 activityBy similarity
    Metal bindingi1123 – 11231ZincBy similarity
    Metal bindingi1125 – 11251ZincBy similarity
    Active sitei1165 – 11651Charge relay system; for serine protease NS3 activityBy similarity
    Metal bindingi1171 – 11711ZincBy similarity
    Metal bindingi1175 – 11751ZincBy similarity
    Sitei1657 – 16582Cleavage; by serine protease NS3Sequence Analysis
    Sitei1711 – 17122Cleavage; by serine protease NS3Sequence Analysis
    Sitei1972 – 19732Cleavage; by serine protease NS3Sequence Analysis
    Metal bindingi2011 – 20111ZincBy similarity
    Metal bindingi2029 – 20291ZincBy similarity
    Metal bindingi2031 – 20311ZincBy similarity
    Metal bindingi2052 – 20521ZincBy similarity
    Sitei2420 – 24212Cleavage; by serine protease NS3Sequence Analysis

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1230 – 12378ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. ATP-dependent helicase activity Source: InterPro
    3. cysteine-type endopeptidase activity Source: InterPro
    4. ion channel activity Source: UniProtKB-KW
    5. protein binding Source: UniProtKB
    6. RNA binding Source: UniProtKB-KW
    7. RNA-directed RNA polymerase activity Source: UniProtKB-KW
    8. serine-type endopeptidase activity Source: InterPro
    9. serine-type exopeptidase activity Source: InterPro
    10. structural molecule activity Source: InterPro
    11. zinc ion binding Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
    3. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
    4. induction by virus of host autophagy Source: UniProtKB-KW
    5. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
    6. pore formation by virus in membrane of host cell Source: UniProtKB-KW
    7. protein oligomerization Source: UniProtKB-KW
    8. regulation of transcription, DNA-templated Source: UniProtKB-KW
    9. suppression by virus of host MAVS activity Source: UniProtKB-KW
    10. suppression by virus of host STAT1 activity Source: UniProtKB-KW
    11. suppression by virus of host TRAF activity Source: UniProtKB-KW
    12. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
    13. transcription, DNA-templated Source: UniProtKB-KW
    14. transformation of host cell by virus Source: InterPro
    15. viral RNA genome replication Source: InterPro
    16. virion attachment to host cell Source: UniProtKB-KW

    Keywords - Molecular functioni

    Helicase, Hydrolase, Ion channel, Nucleotidyltransferase, Protease, Ribonucleoprotein, RNA-directed RNA polymerase, Serine protease, Thiol protease, Transferase, Viral ion channel

    Keywords - Biological processi

    Activation of host autophagy by virus, Apoptosis, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Inhibition of host STAT1 by virus, Inhibition of host TRAFs by virus, Interferon antiviral system evasion, Ion transport, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Transport, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Viral nucleoprotein, Zinc

    Enzyme and pathway databases

    SABIO-RKP26664.

    Protein family/group databases

    MEROPSiC18.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Genome polyprotein
    Cleaved into the following 11 chains:
    Alternative name(s):
    Capsid protein C
    p21
    Alternative name(s):
    gp32
    gp35
    Alternative name(s):
    NS1
    gp68
    gp70
    Protease NS2-3 (EC:3.4.22.-)
    Short name:
    p23
    Alternative name(s):
    Hepacivirin
    NS3P
    p70
    Alternative name(s):
    p8
    Alternative name(s):
    p27
    Alternative name(s):
    p56
    Alternative name(s):
    NS5B
    p68
    OrganismiHepatitis C virus genotype 1a (isolate 1) (HCV)
    Taxonomic identifieri11104 [NCBI]
    Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000007410: Genome, UP000008855: Genome

    Subcellular locationi

    Chain Core protein p21 : Host endoplasmic reticulum membrane; Single-pass membrane protein. Host mitochondrion membrane; Single-pass type I membrane protein. Host lipid droplet
    Note: The C-terminal transmembrane domain of core protein p21 contains an ER signal leading the nascent polyprotein to the ER membrane. Only a minor proportion of core protein is present in the nucleus and an unknown proportion is secreted.
    Chain Envelope glycoprotein E1 : Virion membrane Curated; Single-pass type I membrane protein Curated. Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
    Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E1 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
    Chain Envelope glycoprotein E2 : Virion membrane Curated; Single-pass type I membrane protein Curated. Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
    Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E2 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
    Chain p7 : Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity. Host cell membrane By similarity
    Note: The C-terminus of p7 membrane domain acts as a signal sequence. After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. Only a fraction localizes to the plasma membrane.
    Chain Serine protease NS3 : Host endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
    Note: NS3 is associated to the ER membrane through its binding to NS4A.
    Chain Non-structural protein 4A : Host endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated
    Note: Host membrane insertion occurs after processing by the NS3 protease.
    Chain Non-structural protein 5A : Host endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity. Host cytoplasmhost perinuclear region By similarity. Host mitochondrion By similarity
    Note: Host membrane insertion occurs after processing by the NS3 protease.
    Chain RNA-directed RNA polymerase : Host endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated
    Note: Host membrane insertion occurs after processing by the NS3 protease.

    GO - Cellular componenti

    1. host cell endoplasmic reticulum membrane Source: UniProtKB-SubCell
    2. host cell lipid particle Source: UniProtKB-SubCell
    3. host cell mitochondrial membrane Source: UniProtKB-SubCell
    4. host cell nucleus Source: UniProtKB-SubCell
    5. host cell perinuclear region of cytoplasm Source: UniProtKB-SubCell
    6. host cell plasma membrane Source: UniProtKB-SubCell
    7. integral component of membrane Source: UniProtKB-KW
    8. integral to membrane of host cell Source: UniProtKB-KW
    9. ribonucleoprotein complex Source: UniProtKB-KW
    10. viral envelope Source: UniProtKB-KW
    11. viral nucleocapsid Source: UniProtKB-KW
    12. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Capsid protein, Host cell membrane, Host cytoplasm, Host endoplasmic reticulum, Host lipid droplet, Host membrane, Host mitochondrion, Host nucleus, Membrane, Secreted, Viral envelope protein, Virion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2001 – 20044PQLP → AQLA: No effect on binding to Src-family kinases. 1 Publication
    Mutagenesisi2315 – 23184PLPP → ALAA: No effect on binding to Src-family kinases. 1 Publication
    Mutagenesisi2322 – 23265PPVPP → APVAA: Complete loss of binding to GRB2 and Src-family kinases. 1 Publication

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed; by host1 Publication
    Chaini2 – 191190Core protein p21Sequence AnalysisPRO_0000037517Add
    BLAST
    Chaini2 – 177176Core protein p19By similarityPRO_0000037518Add
    BLAST
    Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityPRO_0000037519Add
    BLAST
    Chaini192 – 383192Envelope glycoprotein E1Sequence AnalysisPRO_0000037520Add
    BLAST
    Chaini384 – 746363Envelope glycoprotein E2Sequence AnalysisPRO_0000037521Add
    BLAST
    Chaini747 – 80963p7By similarityPRO_0000037522Add
    BLAST
    Chaini810 – 1026217Protease NS2-3PROSITE-ProRule annotationPRO_0000037523Add
    BLAST
    Chaini1027 – 1657631Serine protease NS3Sequence AnalysisPRO_0000037524Add
    BLAST
    Chaini1658 – 171154Non-structural protein 4ASequence AnalysisPRO_0000037525Add
    BLAST
    Chaini1712 – 1972261Non-structural protein 4BSequence AnalysisPRO_0000037526Add
    BLAST
    Chaini1973 – 2420448Non-structural protein 5ASequence AnalysisPRO_0000037527Add
    BLAST
    Chaini2421 – 3011591RNA-directed RNA polymeraseSequence AnalysisPRO_0000037528Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine; by hostBy similarity
    Modified residuei53 – 531Phosphoserine; by hostBy similarity
    Modified residuei99 – 991Phosphoserine; by hostBy similarity
    Modified residuei116 – 1161Phosphoserine; by host PKABy similarity
    Glycosylationi196 – 1961N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi209 – 2091N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi234 – 2341N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi305 – 3051N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi417 – 4171N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi423 – 4231N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi430 – 4301N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi448 – 4481N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi476 – 4761N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi532 – 5321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi540 – 5401N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi556 – 5561N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi576 – 5761N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi623 – 6231N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi645 – 6451N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi1968 – 19681S-palmitoyl cysteine; by hostBy similarity
    Lipidationi1972 – 19721S-palmitoyl cysteine; by hostBy similarity
    Disulfide bondi2114 ↔ 2162By similarity
    Modified residuei2194 – 21941Phosphoserine; by host; in p56By similarity
    Modified residuei2197 – 21971Phosphoserine; by host; in p58By similarity
    Modified residuei2201 – 22011Phosphoserine; by host; in p58By similarity
    Modified residuei2204 – 22041Phosphoserine; by host; in p58By similarity
    Modified residuei2321 – 23211Phosphoserine; by hostBy similarity

    Post-translational modificationi

    Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases. The core protein is synthesized as a 21 kDa precursor which is retained in the ER membrane through the hydrophobic signal peptide. Cleavage by the signal peptidase releases the 19 kDa mature core protein. The other proteins (p7, NS2-3, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases By similarity.By similarity
    Envelope E1 and E2 glycoproteins are highly N-glycosylated.By similarity
    Core protein is phosphorylated by host PKC and PKA.By similarity
    NS5A is phosphorylated in a basal form termed p56. p58 is a hyperphosphorylated form of p56. p56 and p58 coexist in the cell in roughly equivalent amounts. Hyperphosphorylation is dependent on the presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6 and CSNK1A1/CKI-alpha kinases may be responsible for NS5A phosphorylation By similarity.By similarity
    NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions By similarity.By similarity
    The N-terminus of a fraction of NS4B molecules seems to be relocated post-translationally from the cytoplasm to the ER lumen, with a 5th transmembrane segment. The C-terminus of NS2 may be lumenal with a fourth transmembrane segment By similarity.By similarity
    Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity

    Keywords - PTMi

    Acetylation, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Miscellaneous databases

    PMAP-CutDBP26664.

    Interactioni

    Subunit structurei

    Core protein is a homomultimer that binds the C-terminal part of E1 and interacts with numerous cellular proteins. Interaction with human STAT1 SH2 domain seems to result in decreased STAT1 phosphorylation, leading to decreased IFN-stimulated gene transcription. In addition to blocking the formation of phosphorylated STAT1, the core protein also promotes ubiquitin-mediated proteasome-dependent degradation of STAT1. Interacts with, and constitutively activates human STAT3. Associates with human LTBR and TNFRSF1A receptors and possibly induces apoptosis. Binds to human SP110 isoform 3/Sp110b, HNRPK, C1QR1, YWHAE, UBE3A/E6AP, DDX3X, APOA2 and RXRA proteins. Interacts with human CREB3 nuclear transcription protein, triggering cell transformation. May interact with human p53. Also binds human cytokeratins KRT8, KRT18, KRT19 and VIM (vimentin). E1 and E2 glycoproteins form a heterodimer that binds to human LDLR, CLDN1, CD81 and SCARB1 receptors. E2 binds and inhibits human EIF2AK2/PKR. Also binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR. p7 forms a homoheptamer in vitro. NS2 forms a homodimer containing a pair of composite active sites at the dimerization interface. NS2 seems to interact with all other non-structural (NS) proteins. NS4A interacts with NS3 serine protease and stabilizes its folding. NS3-NS4A complex is essential for the activation of the latter and allows membrane anchorage of NS3. NS3 interacts with human TANK-binding kinase TBK1 and MAVS. NS4B and NS5A form homodimers and seem to interact with all other non-structural (NS) proteins. NS5A also interacts with human EIF2AK2/PKR, FKBP8, GRB2, BIN1, PIK3R1, SRCAP, VAPB and with most Src-family kinases. NS5B is a homooligomer and interacts with human VAPB, HNRNPA1 and SEPT6 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Acy3Q91XE46EBI-6941357,EBI-7378963From a different organism.
    DDX3XO005713EBI-9209740,EBI-353779From a different organism.
    STAT1P422245EBI-6941357,EBI-1057697From a different organism.

    Protein-protein interaction databases

    IntActiP26664. 4 interactions.
    MINTiMINT-97561.

    Structurei

    Secondary structure

    1
    3011
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1032 – 10354
    Helixi1039 – 104810
    Beta strandi1057 – 10637
    Beta strandi1068 – 10747
    Beta strandi1077 – 10804
    Helixi1082 – 10854
    Beta strandi1090 – 10923
    Beta strandi1095 – 10973
    Beta strandi1100 – 11034
    Turni1104 – 11074
    Beta strandi1108 – 11125
    Beta strandi1129 – 11335
    Beta strandi1139 – 11446
    Beta strandi1146 – 115712
    Helixi1158 – 11603
    Turni1161 – 11633
    Beta strandi1168 – 11703
    Turni1172 – 11743
    Beta strandi1176 – 118611
    Beta strandi1189 – 11979
    Helixi1198 – 12058
    Beta strandi1680 – 168910
    Beta strandi2422 – 24265
    Helixi2445 – 24506
    Helixi2454 – 24563
    Beta strandi2457 – 24593
    Helixi2462 – 24643
    Helixi2465 – 24728
    Helixi2482 – 249514
    Helixi2505 – 25106
    Helixi2525 – 25295
    Helixi2533 – 254816
    Beta strandi2550 – 25523
    Beta strandi2556 – 25605
    Beta strandi2564 – 25663
    Beta strandi2579 – 25824
    Helixi2585 – 260723
    Helixi2608 – 26103
    Helixi2612 – 26143
    Helixi2617 – 263014
    Beta strandi2631 – 26399
    Helixi2644 – 26474
    Helixi2650 – 266011
    Helixi2667 – 267913
    Turni2680 – 26823
    Beta strandi2684 – 26874
    Beta strandi2693 – 26975
    Helixi2707 – 272519
    Beta strandi2729 – 27368
    Beta strandi2739 – 27457
    Helixi2749 – 276517
    Beta strandi2770 – 27723
    Beta strandi2777 – 27793
    Helixi2780 – 27823
    Beta strandi2788 – 27947
    Beta strandi2800 – 28067
    Helixi2809 – 282012
    Helixi2827 – 28359
    Helixi2839 – 28435
    Helixi2845 – 285511
    Beta strandi2863 – 28675
    Beta strandi2870 – 28745
    Helixi2876 – 28783
    Helixi2879 – 28879
    Helixi2889 – 28924
    Helixi2899 – 291214
    Helixi2917 – 293317
    Helixi2936 – 294510
    Helixi2947 – 29493
    Helixi2960 – 29645
    Turni2968 – 29714
    Beta strandi2972 – 29754

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1RTLX-ray2.75A/B1027-1207[»]
    2A4GX-ray2.50A/C1027-1207[»]
    2GVFX-ray2.50A/C1027-1207[»]
    B/D1680-1696[»]
    3EYDX-ray2.30A/C1027-1207[»]
    B/D1680-1696[»]
    3HKWX-ray1.55A/B/C2421-2990[»]
    3KN2X-ray2.30A/C1027-1207[»]
    3QGHX-ray2.14A2421-2990[»]
    3QGIX-ray1.80A2421-2990[»]
    3RC4X-ray1.50A1030-1208[»]
    3RC5X-ray1.60A1030-1208[»]
    ProteinModelPortaliP26664.
    SMRiP26664. Positions 16-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP26664.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini2 – 168167CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini190 – 358169LumenalSequence AnalysisAdd
    BLAST
    Topological domaini380 – 725346LumenalSequence AnalysisAdd
    BLAST
    Topological domaini747 – 75711LumenalSequence AnalysisAdd
    BLAST
    Topological domaini779 – 7824CytoplasmicSequence Analysis
    Topological domaini804 – 81310LumenalSequence Analysis
    Topological domaini835 – 88147CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini903 – 92826LumenalSequence AnalysisAdd
    BLAST
    Topological domaini950 – 1657708CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1679 – 1805127CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1827 – 18282LumenalSequence Analysis
    Topological domaini1850 – 18501CytoplasmicSequence Analysis
    Topological domaini1872 – 188110LumenalSequence Analysis
    Topological domaini1903 – 197270CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini2003 – 2990988CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei1973 – 200230Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei169 – 18921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei359 – 37921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei726 – 74621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei758 – 77821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei783 – 80321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei814 – 83421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei882 – 90221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei929 – 94921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1658 – 167821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1806 – 182621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1829 – 184921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1851 – 187121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1882 – 190221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei2991 – 301121HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini899 – 1026128Peptidase C18PROSITE-ProRule annotationAdd
    BLAST
    Domaini1217 – 1369153Helicase ATP-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini2634 – 2752119RdRp catalyticPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 5958Interaction with DDX3XBy similarityAdd
    BLAST
    Regioni2 – 2322Interaction with STAT1By similarityAdd
    BLAST
    Regioni122 – 17352Interaction with APOA2By similarityAdd
    BLAST
    Regioni150 – 15910Mitochondrial targeting signalCurated
    Regioni164 – 1674Important for lipid droplets localizationBy similarity
    Regioni265 – 29632Fusion peptideSequence AnalysisAdd
    BLAST
    Regioni385 – 41127HVR1By similarityAdd
    BLAST
    Regioni475 – 4817HVR2By similarity
    Regioni482 – 49413CD81-binding 1Sequence AnalysisAdd
    BLAST
    Regioni522 – 55332CD81-binding 2Sequence AnalysisAdd
    BLAST
    Regioni660 – 67112PKR/eIF2-alpha phosphorylation homology domain (PePHD)Add
    BLAST
    Regioni1679 – 169012NS3-binding (by NS4A)Sequence AnalysisAdd
    BLAST
    Regioni2120 – 2332213Transcriptional activationSequence AnalysisAdd
    BLAST
    Regioni2120 – 220889FKBP8-bindingSequence AnalysisAdd
    BLAST
    Regioni2200 – 225051Basal phosphorylationBy similarityAdd
    BLAST
    Regioni2210 – 227566PKR-bindingSequence AnalysisAdd
    BLAST
    Regioni2249 – 230658NS4B-bindingSequence AnalysisAdd
    BLAST
    Regioni2351 – 242070Basal phosphorylationBy similarityAdd
    BLAST
    Regioni2354 – 237724V3By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi5 – 139Nuclear localization signalSequence Analysis
    Motifi38 – 436Nuclear localization signalSequence Analysis
    Motifi58 – 647Nuclear localization signalSequence Analysis
    Motifi66 – 716Nuclear localization signalSequence Analysis
    Motifi1316 – 13194DECH box
    Motifi2322 – 23254SH3-bindingSequence Analysis
    Motifi2327 – 23359Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi796 – 8038Poly-Leu
    Compositional biasi1432 – 14354Poly-Val
    Compositional biasi2286 – 232742Pro-richAdd
    BLAST
    Compositional biasi2996 – 29994Poly-Leu

    Domaini

    The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2). E2 also contain two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2 and CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy By similarity.By similarity
    The N-terminus of NS5A acts as membrane anchor. The central part of NS5A seems to be intrinsically disordered and interacts with NS5B and host PKR. The C-terminus of NS5A contains a variable region called variable region 3 (V3) By similarity.By similarity
    The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases.
    The N-terminal one-third of serine protease NS3 contains the protease activity. This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role. This region is essential for the activity of protease NS2-3, maybe by contributing to the folding of the latter. The helicase activity is located in the C-terminus of NS3 By similarity.By similarity

    Sequence similaritiesi

    Belongs to the hepacivirus polyprotein family.Curated
    Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
    Contains 1 peptidase C18 domain.PROSITE-ProRule annotation
    Contains 1 peptidase S29 domain.Curated
    Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH3-binding, Transmembrane, Transmembrane helix

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    InterProiIPR011492. DEAD_Flavivir.
    IPR002521. HCV_core_C.
    IPR002522. HCV_core_N.
    IPR002519. HCV_env.
    IPR002531. HCV_NS1.
    IPR002518. HCV_NS2.
    IPR000745. HCV_NS4a.
    IPR001490. HCV_NS4b.
    IPR002868. HCV_NS5a.
    IPR013193. HCV_NS5a_1B_dom.
    IPR024350. HCV_NS5a_C.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR013192. NS5A_1a.
    IPR027417. P-loop_NTPase.
    IPR004109. Peptidase_S29.
    IPR007094. RNA-dir_pol_PSvirus.
    IPR002166. RNA_pol_HCV.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view]
    PfamiPF07652. Flavi_DEAD. 1 hit.
    PF01543. HCV_capsid. 1 hit.
    PF01542. HCV_core. 1 hit.
    PF01539. HCV_env. 1 hit.
    PF01560. HCV_NS1. 1 hit.
    PF01538. HCV_NS2. 1 hit.
    PF01006. HCV_NS4a. 1 hit.
    PF01001. HCV_NS4b. 1 hit.
    PF01506. HCV_NS5a. 1 hit.
    PF08300. HCV_NS5a_1a. 1 hit.
    PF08301. HCV_NS5a_1b. 1 hit.
    PF12941. HCV_NS5a_C. 1 hit.
    PF02907. Peptidase_S29. 1 hit.
    PF00998. RdRP_3. 1 hit.
    [Graphical view]
    ProDomiPD001388. HCV_env. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00487. DEXDc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    SSF52540. SSF52540. 2 hits.
    PROSITEiPS51693. HCV_NS2_PRO. 1 hit.
    PS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS50507. RDRP_SSRNA_POS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by ribosomal frameshifting. Align

    Note: The exact location of the ribosomal frameshift is unknown. The F protein seems to be generated by a -2 ribosomal frameshift located in the vicinity of codon 11 of the core protein coding sequence. However, some F proteins may also be generated by +1 ribosomal frameshift. Since the core gene encodes alternative reading frame proteins (ARFPs), many functions depicted for the core protein might belong to the ARFPs.

    Isoform Genome polyprotein (identifier: P26664-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSTNPKPQKK NKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
    KTSERSQPRG RRQPIPKARR PEGRTWAQPG YPWPLYGNEG CGWAGWLLSP 100
    RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
    LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTVPAS AYQVRNSTGL 200
    YHVTNDCPNS SIVYEAADAI LHTPGCVPCV REGNASRCWV AMTPTVATRD 250
    GKLPATQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRRHWT 300
    TQGCNCSIYP GHITGHRMAW DMMMNWSPTT ALVMAQLLRI PQAILDMIAG 350
    AHWGVLAGIA YFSMVGNWAK VLVVLLLFAG VDAETHVTGG SAGHTVSGFV 400
    SLLAPGAKQN VQLINTNGSW HLNSTALNCN DSLNTGWLAG LFYHHKFNSS 450
    GCPERLASCR PLTDFDQGWG PISYANGSGP DQRPYCWHYP PKPCGIVPAK 500
    SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ENDTDVFVLN NTRPPLGNWF 550
    GCTWMNSTGF TKVCGAPPCV IGGAGNNTLH CPTDCFRKHP DATYSRCGSG 600
    PWITPRCLVD YPYRLWHYPC TINYTIFKIR MYVGGVEHRL EAACNWTRGE 650
    RCDLEDRDRS ELSPLLLTTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ 700
    YLYGVGSSIA SWAIKWEYVV LLFLLLADAR VCSCLWMMLL ISQAEAALEN 750
    LVILNAASLA GTHGLVSFLV FFCFAWYLKG KWVPGAVYTF YGMWPLLLLL 800
    LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS WCLWWLQYFL 850
    TRVEAQLHVW IPPLNVRGGR DAVILLMCAV HPTLVFDITK LLLAVFGPLW 900
    ILQASLLKVP YFVRVQGLLR FCALARKMIG GHYVQMVIIK LGALTGTYVY 950
    NHLTPLRDWA HNGLRDLAVA VEPVVFSQME TKLITWGADT AACGDIINGL 1000
    PVSARRGREI LLGPADGMVS KGWRLLAPIT AYAQQTRGLL GCIITSLTGR 1050
    DKNQVEGEVQ IVSTAAQTFL ATCINGVCWT VYHGAGTRTI ASPKGPVIQM 1100
    YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI PVRRRGDSRG 1150
    SLLSPRPISY LKGSSGGPLL CPAGHAVGIF RAAVCTRGVA KAVDFIPVEN 1200
    LETTMRSPVF TDNSSPPVVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK 1250
    VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGSP ITYSTYGKFL 1300
    ADGGCSGGAY DIIICDECHS TDATSILGIG TVLDQAETAG ARLVVLATAT 1350
    PPGSVTVPHP NIEEVALSTT GEIPFYGKAI PLEVIKGGRH LIFCHSKKKC 1400
    DELAAKLVAL GINAVAYYRG LDVSVIPTSG DVVVVATDAL MTGYTGDFDS 1450
    VIDCNTCVTQ TVDFSLDPTF TIETITLPQD AVSRTQRRGR TGRGKPGIYR 1500
    FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV 1550
    CQDHLEFWEG VFTGLTHIDA HFLSQTKQSG ENLPYLVAYQ ATVCARAQAP 1600
    PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEITLTHP VTKYIMTCMS 1650
    ADLEVVTSTW VLVGGVLAAL AAYCLSTGCV VIVGRVVLSG KPAIIPDREV 1700
    LYREFDEMEE CSQHLPYIEQ GMMLAEQFKQ KALGLLQTAS RQAEVIAPAV 1750
    QTNWQKLETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTAAVTSP 1800
    LTTSQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAAIG SVGLGKVLID 1850
    ILAGYGAGVA GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALVVGVVCAA 1900
    ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTAILSS 1950
    LTVTQLLRRL HQWISSECTT PCSGSWLRDI WDWICEVLSD FKTWLKAKLM 2000
    PQLPGIPFVS CQRGYKGVWR VDGIMHTRCH CGAEITGHVK NGTMRIVGPR 2050
    TCRNMWSGTF PINAYTTGPC TPLPAPNYTF ALWRVSAEEY VEIRQVGDFH 2100
    YVTGMTTDNL KCPCQVPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG 2150
    LHEYPVGSQL PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSVAS 2200
    SSASQLSAPS LKATCTANHD SPDAELIEAN LLWRQEMGGN ITRVESENKV 2250
    VILDSFDPLV AEEDEREISV PAEILRKSRR FAQALPVWAR PDYNPPLVET 2300
    WKKPDYEPPV VHGCPLPPPK SPPVPPPRKK RTVVLTESTL STALAELATR 2350
    SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DAESYSSMPP LEGEPGDPDL 2400
    SDGSWSTVSS EANAEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL 2450
    LRHHNLVYST TSRSACQRQK KVTFDRLQVL DSHYQDVLKE VKAAASKVKA 2500
    NLLSVEEACS LTPPHSAKSK FGYGAKDVRC HARKAVTHIN SVWKDLLEDN 2550
    VTPIDTTIMA KNEVFCVQPE KGGRKPARLI VFPDLGVRVC EKMALYDVVT 2600
    KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGFSYD TRCFDSTVTE 2650
    SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR 2700
    ASGVLTTSCG NTLTCYIKAR AACRAAGLQD CTMLVCGDDL VVICESAGVQ 2750
    EDAASLRAFT EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR 2800
    VYYLTRDPTT PLARAAWETA RHTPVNSWLG NIIMFAPTLW ARMILMTHFF 2850
    SVLIARDQLE QALDCEIYGA CYSIEPLDLP PIIQRLHGLS AFSLHSYSPG 2900
    EINRVAACLR KLGVPPLRAW RHRARSVRAR LLARGGRAAI CGKYLFNWAV 2950
    RTKLKLTPIA AAGQLDLSGW FTAGYSGGDI YHSVSHARPR WIWFCLLLLA 3000
    AGVGIYLLPN R 3011

    Note: Produced by conventional translation.

    Length:3,011
    Mass (Da):327,202
    Last modified:January 23, 2007 - v3
    Checksum:i65F8C9447FCE5AF9
    GO
    Isoform F protein (identifier: P0C044-1) [UniParc]FASTAAdd to Basket

    Also known as: Frameshifted protein

    The sequence of this isoform can be found in the external entry P0C044.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

    Note: Produced by ribosomal frameshifting.

    Length:162
    Mass (Da):17,002
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti9 – 113KKN → RKT in infectious clone pHCV-1/SF.
    Natural varianti399 – 3991F → S in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti402 – 4021L → F in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti929 – 9291I → A in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti1703 – 17031R → Q in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti2021 – 20211V → G in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti2349 – 23502TR → IK in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti2378 – 23781P → R in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti2413 – 24131N → S in strain: Isolate infectious clone pHCV-1/SF.
    Natural varianti2992 – 29921I → F in strain: Isolate infectious clone pHCV-1/SF.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M62321 Genomic RNA. Translation: AAA45676.1.
    AF271632 Genomic RNA. Translation: AAF81759.1.
    PIRiA39166. GNWVC3.

    Keywords - Coding sequence diversityi

    Ribosomal frameshifting

    Cross-referencesi

    Web resourcesi

    euHCVdb

    The European HCV database

    Virus Pathogen Resource

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M62321 Genomic RNA. Translation: AAA45676.1 .
    AF271632 Genomic RNA. Translation: AAF81759.1 .
    PIRi A39166. GNWVC3.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1RTL X-ray 2.75 A/B 1027-1207 [» ]
    2A4G X-ray 2.50 A/C 1027-1207 [» ]
    2GVF X-ray 2.50 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    3EYD X-ray 2.30 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    3HKW X-ray 1.55 A/B/C 2421-2990 [» ]
    3KN2 X-ray 2.30 A/C 1027-1207 [» ]
    3QGH X-ray 2.14 A 2421-2990 [» ]
    3QGI X-ray 1.80 A 2421-2990 [» ]
    3RC4 X-ray 1.50 A 1030-1208 [» ]
    3RC5 X-ray 1.60 A 1030-1208 [» ]
    ProteinModelPortali P26664.
    SMRi P26664. Positions 16-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P26664. 4 interactions.
    MINTi MINT-97561.

    Chemistry

    ChEMBLi CHEMBL4620.

    Protein family/group databases

    MEROPSi C18.001.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    euHCVdbi AF271632.
    M62321.

    Enzyme and pathway databases

    SABIO-RK P26664.

    Miscellaneous databases

    EvolutionaryTracei P26664.
    PMAP-CutDB P26664.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    InterProi IPR011492. DEAD_Flavivir.
    IPR002521. HCV_core_C.
    IPR002522. HCV_core_N.
    IPR002519. HCV_env.
    IPR002531. HCV_NS1.
    IPR002518. HCV_NS2.
    IPR000745. HCV_NS4a.
    IPR001490. HCV_NS4b.
    IPR002868. HCV_NS5a.
    IPR013193. HCV_NS5a_1B_dom.
    IPR024350. HCV_NS5a_C.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR013192. NS5A_1a.
    IPR027417. P-loop_NTPase.
    IPR004109. Peptidase_S29.
    IPR007094. RNA-dir_pol_PSvirus.
    IPR002166. RNA_pol_HCV.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view ]
    Pfami PF07652. Flavi_DEAD. 1 hit.
    PF01543. HCV_capsid. 1 hit.
    PF01542. HCV_core. 1 hit.
    PF01539. HCV_env. 1 hit.
    PF01560. HCV_NS1. 1 hit.
    PF01538. HCV_NS2. 1 hit.
    PF01006. HCV_NS4a. 1 hit.
    PF01001. HCV_NS4b. 1 hit.
    PF01506. HCV_NS5a. 1 hit.
    PF08300. HCV_NS5a_1a. 1 hit.
    PF08301. HCV_NS5a_1b. 1 hit.
    PF12941. HCV_NS5a_C. 1 hit.
    PF02907. Peptidase_S29. 1 hit.
    PF00998. RdRP_3. 1 hit.
    [Graphical view ]
    ProDomi PD001388. HCV_env. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00487. DEXDc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50494. SSF50494. 1 hit.
    SSF52540. SSF52540. 2 hits.
    PROSITEi PS51693. HCV_NS2_PRO. 1 hit.
    PS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS50507. RDRP_SSRNA_POS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Infectious cDNA clone of the hepatitis C virus genotype 1 prototype sequence."
      Lanford R.E., Lee H., Chavez D., Guerra B., Brasky K.M.
      J. Gen. Virol. 82:1291-1297(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Infectious clone pHCV-1/SF.
    3. "Differential subcellular localization of hepatitis C virus core gene products."
      Lo S.-Y., Masiarz F., Hwang S.B., Lai M.M.C., Ou J.-H.
      Virology 213:455-461(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION OF CORE PROTEIN.
    4. "Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein."
      Ray R.B., Lagging L.M., Meyer K., Steele R., Ray R.
      Virus Res. 37:209-220(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF CORE PROTEIN.
    5. "Interaction between hepatitis C virus core protein and E1 envelope protein."
      Lo S.-Y., Selby M.J., Ou J.-H.
      J. Virol. 70:5177-5182(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF CORE PROTEIN WITH E1 PROTEIN.
    6. "Suppression of apoptotic cell death by hepatitis C virus core protein."
      Ray R.B., Meyer K., Ray R.
      Virology 226:176-182(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF CORE PROTEIN.
    7. "Transcriptional repression of p53 promoter by hepatitis C virus core protein."
      Ray R.B., Steele R., Meyer K., Ray R.
      J. Biol. Chem. 272:10983-10986(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF CORE PROTEIN.
    8. "Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein."
      Gale M.J. Jr., Korth M.J., Tang N.M., Tan S.-L., Hopkins D.A., Dever T.E., Polyak S.J., Gretch D.R., Katze M.G.
      Virology 230:217-227(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF NS5A WITH HUMAN EIF2AK2/PKR.
    9. "Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity."
      Ray R.B., Steele R., Meyer K., Ray R.
      Gene 208:331-336(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF CORE PROTEIN.
    10. "Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors."
      Shrivastava A., Manna S.K., Ray R., Aggarwal B.B.
      J. Virol. 72:9722-9728(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF CORE PROTEIN.
    11. "Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein."
      Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M.C.
      Science 285:107-110(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF E2 WITH HUMAN EIF2AK2/PKR.
    12. "Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain."
      Taylor D.R., Tian B., Romano P.R., Hinnebusch A.G., Lai M.M.C., Mathews M.B.
      J. Virol. 75:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF E2.
    13. "Membrane topology of the hepatitis C virus NS2 protein."
      Yamaga A.K., Ou J.-H.
      J. Biol. Chem. 277:33228-33234(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY OF NS2 PROTEIN.
    14. "The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity."
      Macdonald A., Crowder K., Street A., McCormick C., Harris M.
      J. Gen. Virol. 85:721-729(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF NS5A WITH HUMAN SRC-FAMILY KINASES, MUTAGENESIS OF 2001-PRO--PRO-2004; 2315-PRO--PRO-2318 AND 2322-PRO--PRO-2326.
    15. "Targeting of hepatitis C virus core protein to mitochondria through a novel C-terminal localization motif."
      Schwer B., Ren S., Pietschmann T., Kartenbeck J., Kaehlcke K., Bartenschlager R., Yen T.S.B., Ott M.
      J. Virol. 78:7958-7968(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN.
    16. "Hepatitis C virus (HCV) NS5A protein downregulates HCV IRES-dependent translation."
      Kalliampakou K.I., Kalamvoki M., Mavromara P.
      J. Gen. Virol. 86:1015-1025(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF NS5A.
    17. "Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes."
      McLauchlan J.
      J. Viral Hepat. 7:2-14(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    18. Cited for: REVIEW, SUBCELLULAR LOCATION.
    19. "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication."
      Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.
      J. Virol. 81:3852-3865(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HNRNPA1 AND SEPT6.

    Entry informationi

    Entry nameiPOLG_HCV1
    AccessioniPrimary (citable) accession number: P26664
    Secondary accession number(s): Q9IFE5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 157 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Cell culture adaptation of the virus leads to mutations in NS5A, reducing its inhibitory effect on replication.By similarity
    Core protein exerts viral interference on hepatitis B virus when HCV and HBV coinfect the same cell, by suppressing HBV gene expression, RNA encapsidation and budding.By similarity

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3