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O92972

- POLG_HCVJ4

UniProt

O92972 - POLG_HCVJ4

Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 2 (20 Feb 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 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
    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
    Sitei2419 – 24202Cleavage; 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: IntAct
    6. protein kinase binding Source: AgBase
    7. RNA binding Source: UniProtKB-KW
    8. RNA-directed RNA polymerase activity Source: UniProtKB-KW
    9. serine-type endopeptidase activity Source: InterPro
    10. serine-type exopeptidase activity Source: InterPro
    11. structural molecule activity Source: InterPro
    12. 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

    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 1b (strain HC-J4) (HCV)
    Taxonomic identifieri420174 [NCBI]
    Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000008094: 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 cytosol Source: AgBase
    2. host cell endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. host cell lipid particle Source: UniProtKB-SubCell
    4. host cell membrane Source: AgBase
    5. host cell mitochondrial membrane Source: UniProtKB-SubCell
    6. host cell nucleus Source: UniProtKB-SubCell
    7. host cell perinuclear region of cytoplasm Source: UniProtKB-SubCell
    8. host cell plasma membrane Source: UniProtKB-SubCell
    9. integral component of membrane Source: UniProtKB-KW
    10. integral to membrane of host cell Source: UniProtKB-KW
    11. ribonucleoprotein complex Source: UniProtKB-KW
    12. viral envelope Source: UniProtKB-KW
    13. viral nucleocapsid Source: UniProtKB-KW
    14. 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_0000278742Add
    BLAST
    Chaini2 – 177176Core protein p19By similarityPRO_0000278743Add
    BLAST
    Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityPRO_0000278744Add
    BLAST
    Chaini192 – 383192Envelope glycoprotein E1Sequence AnalysisPRO_0000278745Add
    BLAST
    Chaini384 – 746363Envelope glycoprotein E2Sequence AnalysisPRO_0000278746Add
    BLAST
    Chaini747 – 80963p7By similarityPRO_0000278747Add
    BLAST
    Chaini810 – 1026217Protease NS2-3PROSITE-ProRule annotationPRO_0000278748Add
    BLAST
    Chaini1027 – 1657631Serine protease NS3Sequence AnalysisPRO_0000278749Add
    BLAST
    Chaini1658 – 171154Non-structural protein 4ASequence AnalysisPRO_0000278750Add
    BLAST
    Chaini1712 – 1972261Non-structural protein 4BSequence AnalysisPRO_0000278751Add
    BLAST
    Chaini1973 – 2419447Non-structural protein 5ASequence AnalysisPRO_0000278752Add
    BLAST
    Chaini2420 – 3010591RNA-directed RNA polymeraseSequence AnalysisPRO_0000278753Add
    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
    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
    Glycosylationi478 – 4781N-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
    Modified residuei2194 – 21941Phosphoserine; by host; in p56Curated
    Modified residuei2197 – 21971Phosphoserine; by host; in p58By similarity
    Modified residuei2201 – 22011Phosphoserine; by host; in p58By similarity
    Modified residuei2204 – 22041Phosphoserine; 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
    Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.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

    Keywords - PTMi

    Acetylation, 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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EIF2AK2P195252EBI-6918883,EBI-640775From a different organism.
    FYNP062412EBI-710506,EBI-515315From a different organism.
    GRB2P629932EBI-710506,EBI-401755From a different organism.
    HCKP086312EBI-710506,EBI-346340From a different organism.
    LckP062402EBI-710506,EBI-1401From a different organism.
    LYNP079482EBI-710506,EBI-79452From a different organism.
    YWHAEP622585EBI-9213553,EBI-356498From a different organism.

    Protein-protein interaction databases

    IntActiO92972. 10 interactions.

    Structurei

    Secondary structure

    1
    3010
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1224 – 12274
    Beta strandi1232 – 12354
    Turni1236 – 12383
    Helixi1239 – 12457
    Turni1246 – 12483
    Beta strandi1251 – 12566
    Helixi1258 – 127013
    Beta strandi1277 – 12793
    Beta strandi1292 – 12954
    Helixi1296 – 13016
    Turni1302 – 13065
    Beta strandi1311 – 13155
    Helixi1323 – 133513
    Helixi1337 – 13393
    Beta strandi1342 – 13465
    Beta strandi1362 – 13665
    Helixi1382 – 13854
    Beta strandi1386 – 13938
    Helixi1397 – 140812
    Turni1409 – 14113
    Beta strandi1414 – 14174
    Helixi1423 – 14253
    Beta strandi1428 – 14369
    Beta strandi1448 – 14536
    Beta strandi1456 – 14627
    Beta strandi1467 – 14693
    Beta strandi1471 – 14788
    Helixi1483 – 14864
    Helixi1488 – 14903
    Beta strandi1491 – 14955
    Beta strandi1497 – 15037
    Helixi1514 – 152512
    Helixi1532 – 154312
    Helixi1555 – 15639
    Helixi1570 – 15778
    Turni1578 – 15803
    Helixi1584 – 159613
    Helixi1615 – 16173
    Beta strandi1627 – 16293
    Helixi1640 – 16489
    Beta strandi2421 – 24255
    Helixi2444 – 24496
    Helixi2453 – 24553
    Beta strandi2456 – 24583
    Helixi2461 – 24633
    Helixi2464 – 24718
    Helixi2481 – 249414
    Helixi2504 – 25096
    Beta strandi2513 – 25153
    Beta strandi2519 – 25213
    Helixi2524 – 25285
    Helixi2532 – 254716
    Beta strandi2549 – 25513
    Beta strandi2555 – 25595
    Beta strandi2563 – 25653
    Turni2568 – 25703
    Beta strandi2578 – 25814
    Helixi2584 – 260623
    Helixi2607 – 26093
    Helixi2611 – 26133
    Helixi2616 – 262914
    Beta strandi2630 – 26389
    Helixi2643 – 26464
    Helixi2649 – 265911
    Helixi2666 – 267813
    Turni2679 – 26813
    Beta strandi2683 – 26864
    Beta strandi2692 – 26965
    Beta strandi2701 – 27033
    Helixi2706 – 272419
    Beta strandi2728 – 27358
    Beta strandi2738 – 27447
    Helixi2748 – 276417
    Beta strandi2769 – 27713
    Beta strandi2776 – 27783
    Helixi2779 – 27813
    Beta strandi2787 – 27937
    Beta strandi2799 – 28057
    Helixi2808 – 281912
    Helixi2826 – 28349
    Helixi2838 – 28425
    Helixi2844 – 285411
    Beta strandi2858 – 28603
    Beta strandi2862 – 28665
    Beta strandi2869 – 28735
    Helixi2875 – 28773
    Helixi2878 – 28869
    Helixi2888 – 28914
    Helixi2898 – 291114
    Helixi2916 – 293318
    Helixi2935 – 294410
    Helixi2946 – 29483
    Beta strandi2949 – 29513
    Helixi2959 – 29635
    Turni2967 – 29704

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1NB4X-ray2.00A/B2420-2989[»]
    1NB6X-ray2.60A/B2420-2989[»]
    1NB7X-ray2.90A/B2420-2989[»]
    2F55X-ray3.30A/B/C1216-1650[»]
    2XHUX-ray2.29A/B2420-2989[»]
    2XHVX-ray1.90A/B2420-2989[»]
    2XHWX-ray2.66A2420-2989[»]
    2YOJX-ray1.76A/B2420-2989[»]
    3CSOX-ray2.71A/B2420-2989[»]
    3GNVX-ray2.75A/B2420-2989[»]
    3GNWX-ray2.39A/B2420-2989[»]
    3GOLX-ray2.85A/B2420-2989[»]
    3HKYX-ray1.90A/B2420-2989[»]
    3LKHX-ray2.05A/B2420-2989[»]
    3MWVX-ray2.20A/B2420-2989[»]
    3MWWX-ray2.80A/B2420-2989[»]
    3SKAX-ray1.73A/B2420-2989[»]
    3SKEX-ray1.97A/B2420-2989[»]
    3SKHX-ray2.50A/B2420-2989[»]
    3TYQX-ray1.60A/B2420-2989[»]
    3TYVX-ray1.65A/B2420-2989[»]
    3U4OX-ray1.77A/B2420-2989[»]
    3U4RX-ray2.00A/B2420-2989[»]
    3UPHX-ray2.00A/B2420-2989[»]
    3UPIX-ray2.00A/B2420-2989[»]
    4DRUX-ray2.10A/B2420-2982[»]
    4EAWX-ray2.00A/B2420-2981[»]
    4GMCX-ray2.70A/B2420-2989[»]
    4IZ0X-ray2.22A/B2420-2989[»]
    4J02X-ray2.00A/B2420-2989[»]
    4J04X-ray2.00A/B2420-2989[»]
    4J06X-ray2.00A/B2420-2989[»]
    4J08X-ray2.10A/B2420-2989[»]
    4J0AX-ray2.40A/B2420-2989[»]
    4JJSX-ray2.20A/B2420-2989[»]
    4JJUX-ray1.91A/B2420-2989[»]
    4JTWX-ray3.00A/B2420-2989[»]
    4JTYX-ray2.60A/B2420-2989[»]
    4JTZX-ray2.80A/B2420-2989[»]
    4JU1X-ray2.90A/B2420-2989[»]
    4JU2X-ray2.70A/B2420-2989[»]
    4JU3X-ray2.00A/B2420-2989[»]
    4JU4X-ray2.40A/B2420-2989[»]
    4JU6X-ray2.20A/B2420-2989[»]
    4JU7X-ray2.20A/B2420-2989[»]
    4JVQX-ray2.40A/B2420-2989[»]
    4JY0X-ray2.20A/B2420-2989[»]
    4JY1X-ray2.60A/B2420-2989[»]
    4MZ4X-ray1.63A/B2420-2989[»]
    ProteinModelPortaliO92972.
    SMRiO92972. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2985.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO92972.

    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 – 2989987CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei1973 – 200230By similarityAdd
    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
    Transmembranei2990 – 301021HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini903 – 1026124Peptidase C18PROSITE-ProRule annotationAdd
    BLAST
    Domaini1217 – 1369153Helicase ATP-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini2633 – 2751119RdRp 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
    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)By similarityAdd
    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
    Regioni2210 – 224940ISDRBy similarityAdd
    BLAST
    Regioni2249 – 230658NS4B-bindingSequence AnalysisAdd
    BLAST
    Regioni2351 – 241969Basal 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 biasi2282 – 232746Pro-richAdd
    BLAST
    Compositional biasi2993 – 29986Poly-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.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.

    O92972-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
    KASERSQPRG RRQPIPKARR PEGRAWAQPG YPWPLYGNEG LGWAGWLLSP 100
    RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
    LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTIPAS AYEVRNVSGI 200
    YHVTNDCSNS SIVYEAADVI MHTPGCVPCV REGNSSRCWV ALTPTLAARN 250
    ASVPTTTIRR HVDLLVGTAA FCSAMYVGDL CGSIFLVSQL FTFSPRRHET 300
    VQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG 350
    AHWGVLAGLA YYSMVGNWAK VLIVALLFAG VDGETHTTGR VAGHTTSGFT 400
    SLFSSGASQK IQLVNTNGSW HINRTALNCN DSLQTGFFAA LFYAHKFNSS 450
    GCPERMASCR PIDWFAQGWG PITYTKPNSS DQRPYCWHYA PRPCGVVPAS 500
    QVCGPVYCFT PSPVVVGTTD RSGVPTYSWG ENETDVMLLN NTRPPQGNWF 550
    GCTWMNSTGF TKTCGGPPCN IGGVGNRTLI CPTDCFRKHP EATYTKCGSG 600
    PWLTPRCLVD YPYRLWHYPC TLNFSIFKVR MYVGGVEHRL NAACNWTRGE 650
    RCNLEDRDRS ELSPLLLSTT EWQILPCAFT TLPALSTGLI HLHQNIVDVQ 700
    YLYGVGSAFV SFAIKWEYIL LLFLLLADAR VCACLWMMLL IAQAEAALEN 750
    LVVLNAASVA GAHGILSFLV FFCAAWYIKG RLAPGAAYAF YGVWPLLLLL 800
    LALPPRAYAL DREMAASCGG AVLVGLVFLT LSPYYKVFLT RLIWWLQYFI 850
    TRAEAHMQVW VPPLNVRGGR DAIILLTCAV HPELIFDITK LLLAILGPLM 900
    VLQAGITRVP YFVRAQGLIR ACMLVRKVAG GHYVQMAFMK LGALTGTYVY 950
    NHLTPLRDWA HAGLRDLAVA VEPVVFSAME TKVITWGADT AACGDIILGL 1000
    PVSARRGKEI FLGPADSLEG QGWRLLAPIT AYSQQTRGVL GCIITSLTGR 1050
    DKNQVEGEVQ VVSTATQSFL ATCINGVCWT VYHGAGSKTL AGPKGPITQM 1100
    YTNVDLDLVG WQAPPGARSM TPCSCGSSDL YLVTRHADVI PVRRRGDSRG 1150
    SLLSPRPVSY LKGSSGGPLL CPSGHVVGVF RAAVCTRGVA KAVDFIPVES 1200
    METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK 1250
    VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGGS ITYSTYGKFL 1300
    ADGGCSGGAY DIIICDECHS TDSTTILGIG TVLDQAETAG ARLVVLATAT 1350
    PPGSVTVPHP NIEEIGLSNN GEIPFYGKAI PIEAIKGGRH LIFCHSKKKC 1400
    DELAAKLTGL GLNAVAYYRG LDVSVIPPIG DVVVVATDAL MTGFTGDFDS 1450
    VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRSGIYR 1500
    FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV 1550
    CQDHLEFWES VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP 1600
    PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEVILTHP ITKYIMACMS 1650
    ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV VIVGRIILSG KPAVVPDREV 1700
    LYQEFDEMEE CASQLPYIEQ GMQLAEQFKQ KALGLLQTAT KQAEAAAPVV 1750
    ESKWRALETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP 1800
    LTTQNTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD 1850
    ILAGYGAGVA GALVAFKVMS GEVPSTEDLV NLLPAILSPG ALVVGVVCAA 1900
    ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTQILSS 1950
    LTITQLLKRL HQWINEDCST PCSGSWLRDV WDWICTVLTD FKTWLQSKLL 2000
    PRLPGVPFLS CQRGYKGVWR GDGIMQTTCP CGAQIAGHVK NGSMRIVGPR 2050
    TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH 2100
    YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPACKPL LREDVTFQVG 2150
    LNQYLVGSQL PCEPEPDVTV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS 2200
    SSASQLSAPS LKATCTTHHD SPDADLIEAN LLWRQEMGGN ITRVESENKV 2250
    VILDSFEPLH AEGDEREISV AAEILRKSRK FPSALPIWAR PDYNPPLLES 2300
    WKDPDYVPPV VHGCPLPPTK APPIPPPRRK RTVVLTESNV SSALAELATK 2350
    TFGSSGSSAV DSGTATALPD LASDDGDKGS DVESYSSMPP LEGEPGDPDL 2400
    SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEESKL PINPLSNSLL 2450
    RHHNMVYATT SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK 2500
    LLSIEEACKL TPPHSAKSKF GYGAKDVRNL SSRAVNHIRS VWEDLLEDTE 2550
    TPIDTTIMAK SEVFCVQPEK GGRKPARLIV FPDLGVRVCE KMALYDVVST 2600
    LPQAVMGSSY GFQYSPKQRV EFLVNTWKSK KCPMGFSYDT RCFDSTVTES 2650
    DIRVEESIYQ CCDLAPEARQ AIRSLTERLY IGGPLTNSKG QNCGYRRCRA 2700
    SGVLTTSCGN TLTCYLKATA ACRAAKLQDC TMLVNGDDLV VICESAGTQE 2750
    DAAALRAFTE AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV 2800
    YYLTRDPTTP LARAAWETAR HTPINSWLGN IIMYAPTLWA RMILMTHFFS 2850
    ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ IIERLHGLSA FTLHSYSPGE 2900
    INRVASCLRK LGVPPLRTWR HRARSVRAKL LSQGGRAATC GRYLFNWAVR 2950
    TKLKLTPIPA ASQLDLSGWF VAGYSGGDIY HSLSRARPRW FPLCLLLLSV 3000
    GVGIYLLPNR 3010
    Length:3,010
    Mass (Da):326,767
    Last modified:February 20, 2007 - v2
    Checksum:i0480D428ABDE9847
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti52 – 521A → T in strain: Isolate pCV-J4L4S and Isolate HC-J4/91.
    Natural varianti70 – 701R → Q in strain: Isolate HC-J4/91.
    Natural varianti231 – 2311R → Q in strain: Isolate pCV-J4L2S and Isolate pCV-J4L6S.
    Natural varianti250 – 2501N → D in strain: Isolate HC-J4/91 and Isolate pCV-J4L4S.
    Natural varianti304 – 3041C → Y in strain: Isolate pCV-J4L2S.
    Natural varianti384 – 3907ETHTTGR → ATYTSGG in strain: Isolate HC-J4/91.
    Natural varianti394 – 3941H → R in strain: Isolate HC-J4/91 and Isolate pCV-J4L4S.
    Natural varianti434 – 4341Q → H in strain: Isolate HC-J4/91.
    Natural varianti438 – 4381F → L in strain: Isolate pCV-J4L4S.
    Natural varianti444 – 4441A → T in strain: Isolate pCV-J4L4S and Isolate HC-J4/91.
    Natural varianti450 – 4501S → P in strain: Isolate pCV-J4L4S.
    Natural varianti464 – 4641W → G in strain: Isolate HC-J4/91.
    Natural varianti476 – 4761K → E in strain: Isolate pCV-J4L4S and Isolate HC-J4/91.
    Natural varianti480 – 4801S → P in strain: Isolate HC-J4/91.
    Natural varianti496 – 4961V → I in strain: Isolate pCV-J4L4S and Isolate HC-J4/91.
    Natural varianti536 – 5361V → M in strain: Isolate pCV-J4L2S.
    Natural varianti934 – 9341V → I in strain: Isolate pCV-J4L2S.
    Natural varianti937 – 9371A → V in strain: Isolate pCV-J4L6S.
    Natural varianti1043 – 10431I → V in strain: Isolate pCV-J4L2S and Isolate pCV-J4L4S.
    Natural varianti1215 – 12151S → T in strain: Isolate pCV-J4L6S.
    Natural varianti1223 – 12231F → S in strain: Isolate pCV-J4L2S.
    Natural varianti1528 – 15281Y → H in strain: Isolate pCV-J4L4S.
    Natural varianti1662 – 16621L → P in strain: Isolate pCV-J4L2S.
    Natural varianti1753 – 17531K → R in strain: Isolate pCV-J4L2S.
    Natural varianti1805 – 18051N → H in strain: Isolate pCV-J4L2S.
    Natural varianti1949 – 19491S → P in strain: Isolate pCV-J4L4S.
    Natural varianti2138 – 21381K → R in strain: Isolate pCV-J4L4S.
    Natural varianti2385 – 23851Y → H in strain: Isolate pCV-J4L4S.
    Natural varianti2785 – 27851C → R in strain: Isolate pCV-J4L2S.
    Natural varianti2824 – 28241I → V in strain: Isolate pCV-J4L2S.
    Natural varianti2999 – 29991S → F in strain: Isolate HC-J4/91.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10750 Genomic RNA. Translation: BAA01583.1.
    AF054247 Genomic RNA. Translation: AAC15722.1.
    AF054248 Genomic RNA. Translation: AAC15723.1.
    AF054249 Genomic RNA. Translation: AAC15724.1.
    AF054250 Genomic RNA. Translation: AAC15725.1.
    PIRiA61196.
    PQ0246.
    PQ0804.
    PS0329.

    Cross-referencesi

    Web resourcesi

    euHCVdb

    The European HCV database

    Virus Pathogen Resource

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10750 Genomic RNA. Translation: BAA01583.1 .
    AF054247 Genomic RNA. Translation: AAC15722.1 .
    AF054248 Genomic RNA. Translation: AAC15723.1 .
    AF054249 Genomic RNA. Translation: AAC15724.1 .
    AF054250 Genomic RNA. Translation: AAC15725.1 .
    PIRi A61196.
    PQ0246.
    PQ0804.
    PS0329.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1NB4 X-ray 2.00 A/B 2420-2989 [» ]
    1NB6 X-ray 2.60 A/B 2420-2989 [» ]
    1NB7 X-ray 2.90 A/B 2420-2989 [» ]
    2F55 X-ray 3.30 A/B/C 1216-1650 [» ]
    2XHU X-ray 2.29 A/B 2420-2989 [» ]
    2XHV X-ray 1.90 A/B 2420-2989 [» ]
    2XHW X-ray 2.66 A 2420-2989 [» ]
    2YOJ X-ray 1.76 A/B 2420-2989 [» ]
    3CSO X-ray 2.71 A/B 2420-2989 [» ]
    3GNV X-ray 2.75 A/B 2420-2989 [» ]
    3GNW X-ray 2.39 A/B 2420-2989 [» ]
    3GOL X-ray 2.85 A/B 2420-2989 [» ]
    3HKY X-ray 1.90 A/B 2420-2989 [» ]
    3LKH X-ray 2.05 A/B 2420-2989 [» ]
    3MWV X-ray 2.20 A/B 2420-2989 [» ]
    3MWW X-ray 2.80 A/B 2420-2989 [» ]
    3SKA X-ray 1.73 A/B 2420-2989 [» ]
    3SKE X-ray 1.97 A/B 2420-2989 [» ]
    3SKH X-ray 2.50 A/B 2420-2989 [» ]
    3TYQ X-ray 1.60 A/B 2420-2989 [» ]
    3TYV X-ray 1.65 A/B 2420-2989 [» ]
    3U4O X-ray 1.77 A/B 2420-2989 [» ]
    3U4R X-ray 2.00 A/B 2420-2989 [» ]
    3UPH X-ray 2.00 A/B 2420-2989 [» ]
    3UPI X-ray 2.00 A/B 2420-2989 [» ]
    4DRU X-ray 2.10 A/B 2420-2982 [» ]
    4EAW X-ray 2.00 A/B 2420-2981 [» ]
    4GMC X-ray 2.70 A/B 2420-2989 [» ]
    4IZ0 X-ray 2.22 A/B 2420-2989 [» ]
    4J02 X-ray 2.00 A/B 2420-2989 [» ]
    4J04 X-ray 2.00 A/B 2420-2989 [» ]
    4J06 X-ray 2.00 A/B 2420-2989 [» ]
    4J08 X-ray 2.10 A/B 2420-2989 [» ]
    4J0A X-ray 2.40 A/B 2420-2989 [» ]
    4JJS X-ray 2.20 A/B 2420-2989 [» ]
    4JJU X-ray 1.91 A/B 2420-2989 [» ]
    4JTW X-ray 3.00 A/B 2420-2989 [» ]
    4JTY X-ray 2.60 A/B 2420-2989 [» ]
    4JTZ X-ray 2.80 A/B 2420-2989 [» ]
    4JU1 X-ray 2.90 A/B 2420-2989 [» ]
    4JU2 X-ray 2.70 A/B 2420-2989 [» ]
    4JU3 X-ray 2.00 A/B 2420-2989 [» ]
    4JU4 X-ray 2.40 A/B 2420-2989 [» ]
    4JU6 X-ray 2.20 A/B 2420-2989 [» ]
    4JU7 X-ray 2.20 A/B 2420-2989 [» ]
    4JVQ X-ray 2.40 A/B 2420-2989 [» ]
    4JY0 X-ray 2.20 A/B 2420-2989 [» ]
    4JY1 X-ray 2.60 A/B 2420-2989 [» ]
    4MZ4 X-ray 1.63 A/B 2420-2989 [» ]
    ProteinModelPortali O92972.
    SMRi O92972. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2985.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O92972. 10 interactions.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    euHCVdbi AF054247.
    AF054248.
    AF054249.
    AF054250.
    D10750.

    Miscellaneous databases

    EvolutionaryTracei O92972.

    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. "Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability."
      Okamoto H., Kojima M., Okada S., Yoshizawa H., Iizuka H., Tanaka T., Muchmore E.E., Peterson D.A., Ito Y., Mishiro S.
      Virology 190:894-899(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate HC-J4/91.
    2. "Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo."
      Yanagi M., St Claire M., Shapiro M., Emerson S.U., Purcell R.H., Bukh J.
      Virology 244:161-172(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: HC-J4, Isolate pCV-J4L2S, Isolate pCV-J4L4S and Isolate pCV-J4L6S.
    3. "Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro."
      Clarke D., Griffin S., Beales L., Gelais C.S., Burgess S., Harris M., Rowlands D.
      J. Biol. Chem. 281:37057-37068(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    4. "Biochemical and pre-steady-state kinetic characterization of the hepatitis C virus RNA polymerase (NS5BDelta21, HC-J4)."
      Cramer J., Jaeger J., Restle T.
      Biochemistry 45:3610-3619(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF NS5B, SUBUNIT.
      Strain: Isolate pCV-J4L6S.
    5. "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.
    6. "Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation."
      O'Farrell D., Trowbridge R., Rowlands D., Jager J.
      J. Mol. Biol. 326:1025-1035(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2420-2989.

    Entry informationi

    Entry nameiPOLG_HCVJ4
    AccessioniPrimary (citable) accession number: O92972
    Secondary accession number(s): O92969
    , O92970, O92971, Q02828
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 20, 2007
    Last sequence update: February 20, 2007
    Last modified: October 1, 2014
    This is version 118 of the entry and version 2 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

    3D-structure, Complete proteome, 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