Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O92531

- POLG_HCVVO

UniProt

O92531 - POLG_HCVVO

Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 6k (isolate VN405) (HCV)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 By similarity.By similarity
    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 By similarity.By similarity
    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
    Sitei748 – 7492Cleavage; by host signal peptidaseBy similarity
    Sitei811 – 8122Cleavage; by host signal peptidaseBy similarity
    Active sitei954 – 9541For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Active sitei974 – 9741For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Active sitei995 – 9951For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation
    Sitei1028 – 10292Cleavage; by protease NS2-3PROSITE-ProRule annotation
    Active sitei1085 – 10851Charge relay system; for serine protease NS3 activityBy similarity
    Active sitei1109 – 11091Charge relay system; for serine protease NS3 activityBy similarity
    Metal bindingi1125 – 11251ZincBy similarity
    Metal bindingi1127 – 11271ZincBy similarity
    Active sitei1167 – 11671Charge relay system; for serine protease NS3 activityBy similarity
    Metal bindingi1173 – 11731ZincBy similarity
    Metal bindingi1177 – 11771ZincBy similarity
    Sitei1659 – 16602Cleavage; by serine protease NS3Sequence Analysis
    Sitei1713 – 17142Cleavage; by serine protease NS3Sequence Analysis
    Sitei1974 – 19752Cleavage; by serine protease NS3Sequence Analysis
    Metal bindingi2013 – 20131ZincBy similarity
    Metal bindingi2031 – 20311ZincBy similarity
    Metal bindingi2033 – 20331ZincBy similarity
    Metal bindingi2054 – 20541ZincBy similarity
    Sitei2425 – 24262Cleavage; by serine protease NS3Sequence Analysis

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1232 – 12398ATPPROSITE-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. RNA binding Source: UniProtKB-KW
    6. RNA-directed RNA polymerase activity Source: UniProtKB-KW
    7. serine-type endopeptidase activity Source: InterPro
    8. serine-type exopeptidase activity Source: InterPro
    9. structural molecule activity Source: InterPro
    10. 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

    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 6k (isolate VN405) (HCV)
    Taxonomic identifieri356425 [NCBI]
    Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000002674: Genome

    Subcellular locationi

    Chain Core protein p21 : Host endoplasmic reticulum membrane By similarity; Single-pass membrane protein By similarity. Host mitochondrion membrane By similarity; Single-pass type I membrane protein By similarity. Host lipid droplet By similarity
    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 Core protein p19 : Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity
    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

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed; by hostBy similarity
    Chaini2 – 191190Core protein p21Sequence AnalysisPRO_0000045724Add
    BLAST
    Chaini2 – 177176Core protein p19By similarityPRO_0000045725Add
    BLAST
    Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityPRO_0000045726Add
    BLAST
    Chaini192 – 383192Envelope glycoprotein E1Sequence AnalysisPRO_0000045727Add
    BLAST
    Chaini384 – 748365Envelope glycoprotein E2Sequence AnalysisPRO_0000045728Add
    BLAST
    Chaini749 – 81163p7By similarityPRO_0000045729Add
    BLAST
    Chaini812 – 1028217Protease NS2-3PROSITE-ProRule annotationPRO_0000045730Add
    BLAST
    Chaini1029 – 1659631Serine protease NS3Sequence AnalysisPRO_0000045731Add
    BLAST
    Chaini1660 – 171354Non-structural protein 4ASequence AnalysisPRO_0000045732Add
    BLAST
    Chaini1714 – 1974261Non-structural protein 4BSequence AnalysisPRO_0000045733Add
    BLAST
    Chaini1975 – 2425451Non-structural protein 5ASequence AnalysisPRO_0000045734Add
    BLAST
    Chaini2426 – 3016591RNA-directed RNA polymeraseSequence AnalysisPRO_0000045735Add
    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
    Glycosylationi250 – 2501N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi305 – 3051N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi416 – 4161N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi422 – 4221N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi429 – 4291N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi447 – 4471N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi475 – 4751N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi532 – 5321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi556 – 5561N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi578 – 5781N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi625 – 6251N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi647 – 6471N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi757 – 7571N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi1974 – 19741S-palmitoyl cysteine; by hostBy similarity
    Disulfide bondi2116 ↔ 2164By similarity
    Modified residuei2196 – 21961Phosphoserine; by host; in p56By similarity
    Modified residuei2199 – 21991Phosphoserine; by host; in p58By similarity
    Modified residuei2203 – 22031Phosphoserine; by host; in p58By similarity
    Modified residuei2206 – 22061Phosphoserine; by host; in p58By 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

    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

    Structurei

    3D structure databases

    ProteinModelPortaliO92531.
    SMRiO92531. Positions 2-45, 904-1028, 1031-1659, 1975-2005, 2010-2172, 2426-2988.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini2 – 168167CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini190 – 358169LumenalSequence AnalysisAdd
    BLAST
    Topological domaini380 – 727348LumenalSequence AnalysisAdd
    BLAST
    Topological domaini749 – 75911LumenalSequence AnalysisAdd
    BLAST
    Topological domaini781 – 7844CytoplasmicSequence Analysis
    Topological domaini806 – 81510LumenalSequence Analysis
    Topological domaini837 – 88347CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini905 – 93026LumenalSequence AnalysisAdd
    BLAST
    Topological domaini952 – 1659708CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1681 – 1807127CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1829 – 18302LumenalSequence Analysis
    Topological domaini1852 – 18521CytoplasmicSequence Analysis
    Topological domaini1874 – 188310LumenalSequence Analysis
    Topological domaini1905 – 197470CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini2005 – 2995991CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei1975 – 200430By similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei169 – 18921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei359 – 37921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei728 – 74821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei760 – 78021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei785 – 80521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei816 – 83621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei884 – 90421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei931 – 95121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1660 – 168021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1808 – 182821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1831 – 185121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1853 – 187321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1884 – 190421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei2996 – 301621HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini905 – 1028124Peptidase C18PROSITE-ProRule annotationAdd
    BLAST
    Domaini1219 – 1371153Helicase ATP-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini2639 – 2757119RdRp 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 signalBy similarity
    Regioni164 – 1674Important for lipid droplets localizationBy similarity
    Regioni265 – 29632Fusion peptideSequence AnalysisAdd
    BLAST
    Regioni384 – 41027HVR1By similarityAdd
    BLAST
    Regioni482 – 49413CD81-binding 1Sequence AnalysisAdd
    BLAST
    Regioni522 – 55332CD81-binding 2Sequence AnalysisAdd
    BLAST
    Regioni662 – 67312PKR/eIF2-alpha phosphorylation homology domain (PePHD)By similarityAdd
    BLAST
    Regioni1681 – 169212NS3-binding (by NS4A)Sequence AnalysisAdd
    BLAST
    Regioni2122 – 2335214Transcriptional activationSequence AnalysisAdd
    BLAST
    Regioni2122 – 221089FKBP8-bindingSequence AnalysisAdd
    BLAST
    Regioni2202 – 225251Basal phosphorylationBy similarityAdd
    BLAST
    Regioni2212 – 227766PKR-bindingSequence AnalysisAdd
    BLAST
    Regioni2251 – 230959NS4B-bindingSequence AnalysisAdd
    BLAST
    Regioni2354 – 242572Basal phosphorylationBy 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
    Motifi1318 – 13214DECH boxBy similarity
    Motifi2325 – 23284SH3-bindingSequence Analysis
    Motifi2330 – 23389Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi798 – 8058Poly-Leu
    Compositional biasi2279 – 233052Pro-richAdd
    BLAST
    Compositional biasi2998 – 30047Poly-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 a highly variable region called hypervariable region 1 (HVR1). E2 also contains two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. 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 By similarity.By similarity
    The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases.By similarity
    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]

    Sequencei

    Sequence statusi: Complete.

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

    O92531-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSTLPKPQRK TKRNTNRRPM DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
    KTSERSQPRG RRQPIPKARQ SQGRHWAQPG YPWPLYGNEG CGWAGWLLSP 100
    RGSRPNWGPN DPRRRSRNLG KVIDTLTCGF ADLMGYIPVV GAPLGGVAAA 150
    LAHGVRAIED GINYATGNLP GCSFSIFLLA LLSCLTTPAS AVHYRNISGI 200
    YHLTNDCPNS SIIYEADNII MHTPGCVPCV KTGNKSQCWV PVAPTLAVAN 250
    ASVPIRGFRS HVDLLVGSAA ACSALYIGDL CGGVFLVGQL FTFRPRQHTT 300
    VQECNCSIYT GHITGHRMAW DMMMNWSPTV TFITSSLLRV PQLLLEIALE 350
    GHWGVIGALL YYSMVANWAK VFAVLLLFAG VDATTHIGSS ASATTNRLTS 400
    FFSPGSKQNV QLIKTNGSWH INRTALNCND SLHTGFIAGL LYAHRFNSSG 450
    CPERLSSCRP LHAFEQGWGP LTYANISGPS NDKPYCWHYP PRPCDIVPAR 500
    SVCGPVYCFT PSPVVVGTTD RKGLPTYTWG ANESDVFLLR STRPPRGSWF 550
    GCTWMNSTGF VKTCGAPPCN TRPVGSGNDT LVCPTDCFRK HPEATYARCG 600
    SGPWLTPRCL VNYPYRLWHY PCTVNYTIHK VRMFVGGIEH RFEAACNWTR 650
    GERCELDDRD RVEMSPLLFS TTQLSILPCS FTTMPALSTG LIHLHQNIVD 700
    VQYLYGVSSA VVSWAVKWEY IVLAFLVLAV ARVCACLWLM FLVGQAEAAL 750
    ENLIVLNATS AAGSQGWVWG VVFICAAWYI RGRAAPITTY AILQLWPLLL 800
    LVLALPRRAY AYNGEEAASL GMLAIVIITI FTLTPAYKTL LISTLWWIQY 850
    YIARAEAMLY VWVPSLQVRG GRDAVILLTC LLHPQLGFEV TKAILALLGP 900
    LYILQYSLLK TPYFVRAHIL LRVCMFLRGV AGGKYVQAAL LRLGAWTGTY 950
    IYDHLTPLSD WACDGLRDLA VAVEPVVFSP MEKKVITWGA DTVACGDIIS 1000
    GLPVSARRGN LIFLGPADDI RDGGWRLLAP ITAYAQQTRG LVGTIVTSLT 1050
    GRDKNEVEGE IQVVSTATQS FLATTVNGVL WTVYHGAGSK TLAGPKGPIC 1100
    QMYTNVDQDL VGWPAPPGAR SLTPCTCGSS DLYLVTRNAD VIPARRRGDT 1150
    RAALLSPRPI STLKGSSGGP MLCPSGHVAG IFRAAVCTRG VAKSLDFVPV 1200
    ENMQSTARSP SFSDNTTPPA VPQTYQVGYL HAPTGSGKST KVPAAYAAQG 1250
    YKVLVLNPSV AATLGFGSYM STAHGIDPNI RTGVRTITTG GAITYSTYGK 1300
    FLADGGCSGG AYDIIICDEC HSTDPTTVLG IGTVLDQAET AGVRLTVLAT 1350
    ATPPGSVTVP HPNITEVALS STGEVPFYGK AIPLEYIKGG RHLIFCHSKK 1400
    KCDELAKQLT SLGLNAVAFY RGVDVSVIPT SGDVVVCATD ALMTGYTGDF 1450
    DSVIDCNVSV TQVVDFSLDP TFTIETTTMP QDAVSRSQRR GRTGRGKHGV 1500
    YRYVSQGERP SGIFDTVVLC EAYDTGCAWY ELTPSETTVR LRAYLNTPGL 1550
    PVCQDHLEFW EGVFTGLTHI DAHLLSQTKQ GGENFAYLVA YQATVCARAK 1600
    APPPSWDTMW KCLIRLKPML TGPTPLLYRL GAVQNEITTT HPITKYIMTC 1650
    MSADLEVITS TWVLVGGVLA ALAAYCLSVG CVVVCGRIST TGKPVLIPDR 1700
    EVLYQQFDEM EECSRHIPYL VEGQHLAEQF KQKVLGLIQT TTRQAEEIEP 1750
    VVHSAWPKLE QFWQKHLWNF VSGIQYLAGL STLPGNPAVA SLMSFSASLT 1800
    SPLSTSTTLL LNILGGWVAS QLANPTASTA FVVSGLAGAT VGSIGLGRVL 1850
    VDIIAGYGAG VSGALVAFKI MSGETPSAED MVNLLPALLS PGALVVGVVC 1900
    AAILRRHAGP AEGATQWMNR LIAFASRGNH VSPTHYVPET DTSRQVMAIL 1950
    SSLTVTSLLR KLHEWINSDW STPCSGSWLR DIWDWVCTVL SDFKVWLKSK 2000
    LVPALPGVPF LSCQRGFRGV WRGDGICRTT CPCGADIVGH VKNGSMRISG 2050
    SRWCSNIWHG TFPINATTTG PSVPIPEPNY KRALWRVSAE EYVEVARVGD 2100
    SHFVVGATNQ DLKCPCQVPA PEFFTEVDGV RLHRFAPACK PLLRDEISFL 2150
    VGLNSYAIGS QLPCEPEPDV TVVTSMLVDP SHLTAEAAAR RLARGSPPSC 2200
    ASSLASQLSA PSLKATCTTH CAHPDADLIE ANLLWRQEVG GNITRVESEN 2250
    KVIVLDSFDP LVPEYDDREP SVPAECHRPN RPKFPPALPI WARPDYNPPL 2300
    LETWKKPDYA PPLVHGCALP SPVQPPVPPP RRKSVVHLDD STVATALAEL 2350
    AEKSFPTQPA STPDSDSGHP TTSKSSDQAD EGEDTPSEAG SYSSMPPLEG 2400
    EPGDPDLSSG SWSTVSEEGD SVVCCSMSYS WTGALVTPCA AEEEKLPINP 2450
    LSNSLIRHHN LVYSTTTRSA AMRQKKVTFD RLQILDQHYN NVVKEVKLRA 2500
    SGVTAKLLSV EEACSLTPPH SARSKFGYGA KDVRSHTSKA INHINSVWED 2550
    LLEDNQTPIP TTIMAKNEVF CADVSKGGRK PARLIVYPDL GVRVCEKRAL 2600
    YDVTRKLPTA IMGDAYGFQY SPKQRVDQLL KMWRSKKTPM GFSYDTRCFD 2650
    STVTEHDIKT ERDVYLSCKL DPVARKAIES LTERLYIGGP MYNSRGQLCG 2700
    TRRCRASGVL TTSLGNTMTC FIKAEAACRA AGLTNYDMLV CGDDLVVIAE 2750
    SAGVQEDASN LRAFTEAMTR YSAPPGDEPH PAYDLELITS CSSNVSVAHD 2800
    HTGQRYYYLT RDPTTPLSRA AWETARHTPV NSWLGNIIMY APAIWVRMVL 2850
    MTHFFQILQA QEQLDKVLDF DMYGVTYSVS PLQLPAIIQR LHGMAAFSLH 2900
    GYSPTELNRV GACLRKLGAP PLRAWRHRAR AVRAKLIAQG GGAAICGKYL 2950
    FNWAVKTKLK LTPIPDAARL DLSGWFISGF SGGDIYHSVS RARPRIFLLC 3000
    LLLLSVGVGI FLLPAR 3016
    Length:3,016
    Mass (Da):328,035
    Last modified:January 23, 2007 - v3
    Checksum:i4E5CFF96258BCE3B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D84264 Genomic RNA. Translation: BAA32666.1.
    PIRiPQ0804.

    Cross-referencesi

    Web resourcesi

    euHCVdb

    The European HCV database

    Virus Pathogen Resource

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D84264 Genomic RNA. Translation: BAA32666.1 .
    PIRi PQ0804.

    3D structure databases

    ProteinModelPortali O92531.
    SMRi O92531. Positions 2-45, 904-1028, 1031-1659, 1975-2005, 2010-2172, 2426-2988.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi C18.001.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    euHCVdbi D84264.

    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. "The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups."
      Tokita H., Okamoto H., Iizuka H., Kishimoto J., Tsuda F., Miyakawa Y., Mayumi M.
      J. Gen. Virol. 79:1847-1857(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "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.
    3. Cited for: REVIEW, SUBCELLULAR LOCATION.
    4. "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_HCVVO
    AccessioniPrimary (citable) accession number: O92531
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 10, 2006
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 114 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

    Caution

    The core gene probably also codes for alternative reading frame proteins (ARFPs). Many functions depicted for the core protein might belong to the ARFPs.Curated

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme

    Documents

    1. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3