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P27958

- POLG_HCVH

UniProt

P27958 - POLG_HCVH

Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1a (isolate H) (HCV)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 168 (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 By similarity.By similarity
    P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine By similarity. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity.By similarity1 Publication
    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 By similarity. Cleaves and inhibits the host antiviral protein MAVS.By similarity1 Publication
    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. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation.1 Publication
    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.1 Publication

    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. Activity is up-regulated by PKN2-mediated phosphorylation.By similarity1 Publication

    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 peptidase
    Sitei809 – 8102Cleavage; by host signal peptidase
    Active sitei952 – 9521For protease NS2-3 activity; shared with dimeric partner
    Active sitei972 – 9721For protease NS2-3 activity; shared with dimeric partner
    Active sitei993 – 9931For protease NS2-3 activity; shared with dimeric partner
    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 – 11231Zinc
    Metal bindingi1125 – 11251Zinc
    Active sitei1165 – 11651Charge relay system; for serine protease NS3 activity
    Metal bindingi1171 – 11711Zinc
    Metal bindingi1175 – 11751Zinc
    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. DEAD/H-box RNA helicase binding Source: AgBase
    5. identical protein binding Source: IntAct
    6. ion channel activity Source: UniProtKB-KW
    7. protein binding Source: IntAct
    8. RNA binding Source: UniProtKB-KW
    9. RNA-directed RNA polymerase activity Source: UniProtKB-KW
    10. serine-type endopeptidase activity Source: InterPro
    11. serine-type exopeptidase activity Source: InterPro
    12. structural molecule activity Source: InterPro
    13. 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. negative regulation of defense response to virus by host Source: AgBase
    7. negative regulation of interleukin-6 production Source: AgBase
    8. negative regulation of toll-like receptor 2 signaling pathway Source: AgBase
    9. negative regulation of toll-like receptor 4 signaling pathway Source: AgBase
    10. negative regulation of toll-like receptor 7 signaling pathway Source: AgBase
    11. negative regulation of toll-like receptor 9 signaling pathway Source: AgBase
    12. pore formation by virus in membrane of host cell Source: UniProtKB-KW
    13. protein oligomerization Source: UniProtKB-KW
    14. regulation of transcription, DNA-templated Source: UniProtKB-KW
    15. suppression by virus of host MAVS activity Source: UniProtKB-KW
    16. suppression by virus of host MAVS activity by MAVS proteolysis Source: AgBase
    17. suppression by virus of host STAT1 activity Source: UniProtKB-KW
    18. suppression by virus of host TRAF activity Source: UniProtKB-KW
    19. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
    20. transcription, DNA-templated Source: UniProtKB-KW
    21. transformation of host cell by virus Source: InterPro
    22. viral protein processing Source: AgBase
    23. viral RNA genome replication Source: InterPro
    24. 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 1a (isolate H) (HCV)
    Taxonomic identifieri11108 [NCBI]
    Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000000518: 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; Single-pass type I membrane protein
    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; Single-pass type I membrane protein
    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 1 Publication; Multi-pass membrane protein 1 Publication. Host cell membrane 1 Publication
    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 4B : Host endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication
    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
    Mutagenesisi720 – 7201V → L: Increases processing between E2 and p7. 1 Publication
    Mutagenesisi779 – 7791K → I: Virus can no longer infect chimpanzee. 1 Publication
    Mutagenesisi781 – 7811R → S: Virus can no longer infect chimpanzee. 1 Publication
    Mutagenesisi952 – 9521H → A: Complete loss of NS2-NS3 cleavage. 2 Publications
    Mutagenesisi993 – 9931C → A: Complete loss of NS2-NS3 cleavage. 2 Publications
    Mutagenesisi1165 – 11651S → A: Complete loss of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B cleavages. 1 Publication
    Mutagenesisi1968 – 19681C → A: Strong decrease in NS4B palmitoylation. 1 Publication
    Mutagenesisi1972 – 19721C → A: Slight decrease in NS4B palmitoylation. 1 Publication
    Mutagenesisi2321 – 23211S → A: Loss of phosphorylation. 1 Publication

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed; by hostBy similarity
    Chaini2 – 191190Core protein p21Sequence AnalysisPRO_0000037566Add
    BLAST
    Chaini2 – 177176Core protein p19By similarityPRO_0000037567Add
    BLAST
    Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityPRO_0000037568Add
    BLAST
    Chaini192 – 383192Envelope glycoprotein E1Sequence AnalysisPRO_0000037569Add
    BLAST
    Chaini384 – 746363Envelope glycoprotein E2Sequence AnalysisPRO_0000037570Add
    BLAST
    Chaini747 – 80963p7PRO_0000037571Add
    BLAST
    Chaini810 – 1026217Protease NS2-3PROSITE-ProRule annotationPRO_0000037572Add
    BLAST
    Chaini1027 – 1657631Serine protease NS3Sequence AnalysisPRO_0000037573Add
    BLAST
    Chaini1658 – 171154Non-structural protein 4ASequence AnalysisPRO_0000037574Add
    BLAST
    Chaini1712 – 1972261Non-structural protein 4BSequence AnalysisPRO_0000037575Add
    BLAST
    Chaini1973 – 2420448Non-structural protein 5ASequence AnalysisPRO_0000037576Add
    BLAST
    Chaini2421 – 3011591RNA-directed RNA polymeraseSequence AnalysisPRO_0000037577Add
    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 host1 Publication
    Lipidationi1972 – 19721S-palmitoyl cysteine; by host; partial1 Publication
    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 host2 Publications

    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.
    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
    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
    NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions.1 Publication

    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. Interacts (via N-terminus finger domain) with human PKN2. 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). Interacts with human ACY3. 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
    P266604EBI-6377335,EBI-6875462From a different organism.
    Q99IB83EBI-8753518,EBI-6858513From a different organism.
    ACTN1P128147EBI-6904388,EBI-351710From a different organism.
    AP2M1Q96CW14EBI-6377335,EBI-297683From a different organism.
    ARAP1Q96P483EBI-8753518,EBI-710003From a different organism.
    ATF6BQ999415EBI-8763498,EBI-2841031From a different organism.
    ATMQ133153EBI-6904388,EBI-495465From a different organism.
    BIN1O0049911EBI-8753518,EBI-719094From a different organism.
    BIN1O00499-72EBI-8753518,EBI-8870146From a different organism.
    C1QBPQ070214EBI-6377335,EBI-347528From a different organism.
    CCDC86Q9H6F53EBI-8753518,EBI-721289From a different organism.
    CD81P600339EBI-6904269,EBI-712921From a different organism.
    CDKN1AP389363EBI-6377335,EBI-375077From a different organism.
    CHEK2O960173EBI-6904388,EBI-1180783From a different organism.
    CIDEBQ9UHD46EBI-6919131,EBI-7062247From a different organism.
    CNXQ920L92EBI-6904269,EBI-9209498From a different organism.
    CRABP1P297623EBI-8753518,EBI-725950From a different organism.
    DDX3XO005714EBI-6377335,EBI-353779From a different organism.
    DDX5P1784412EBI-6904388,EBI-351962From a different organism.
    EIF2AK2P195255EBI-8753518,EBI-640775From a different organism.
    Eif2ak3Q9Z2B55EBI-6904269,EBI-1226344From a different organism.
    EIF4A2Q142404EBI-6904388,EBI-73473From a different organism.
    ERC1Q8IUD2-38EBI-3649474,EBI-9352449From a different organism.
    ERC1Q8IUD2-43EBI-3649474,EBI-9352501From a different organism.
    FGBP026754EBI-6377335,EBI-1034445From a different organism.
    FYNP062414EBI-706378,EBI-515315From a different organism.
    GRB2P629933EBI-706378,EBI-401755From a different organism.
    HCKP086315EBI-706378,EBI-346340From a different organism.
    HNRNPA1P096514EBI-6904388,EBI-352662From a different organism.
    HSPA5P078233EBI-6904269,EBI-371776From a different organism.
    IKBKEQ141642EBI-6919131,EBI-307369From a different organism.
    IPO5O004105EBI-8753518,EBI-356424From a different organism.
    LckP062403EBI-706378,EBI-1401From a different organism.
    LTFP027884EBI-6904269,EBI-1058602From a different organism.
    LYNP079485EBI-706378,EBI-79452From a different organism.
    MAPKAPK3Q166445EBI-6377335,EBI-1384657From a different organism.
    NCLP193384EBI-6904388,EBI-346967From a different organism.
    PI4KAP423567EBI-8753518,EBI-723050From a different organism.
    PMLP295906EBI-6377335,EBI-295890From a different organism.
    PSMB8P280624EBI-3649474,EBI-372294From a different organism.
    SCARB1Q8WTV02EBI-6904269,EBI-78657From a different organism.
    SEPT6Q141414EBI-6904388,EBI-745901From a different organism.
    SNRPD1P623147EBI-3649474,EBI-372177From a different organism.
    STAT1P422242EBI-6377335,EBI-1057697From a different organism.
    TBC1D20Q96BZ911EBI-8753518,EBI-9254454From a different organism.
    TBK1Q9UHD22EBI-6919131,EBI-356402From a different organism.
    TMEM173Q86WV65EBI-8763498,EBI-2800345From a different organism.
    Traf2P394295EBI-8753518,EBI-520016From a different organism.
    VAPAQ9P0L05EBI-6904388,EBI-1059156From a different organism.

    Protein-protein interaction databases

    IntActiP27958. 215 interactions.
    MINTiMINT-106294.

    Structurei

    Secondary structure

    1
    3011
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi10 – 123
    Beta strandi16 – 183
    Turni19 – 235
    Beta strandi30 – 356
    Turni36 – 383
    Beta strandi39 – 413
    Helixi422 – 4243
    Beta strandi425 – 4273
    Turni432 – 4354
    Turni437 – 4426
    Beta strandi496 – 4983
    Helixi499 – 5013
    Beta strandi502 – 5043
    Beta strandi507 – 5159
    Beta strandi532 – 5343
    Beta strandi536 – 5383
    Beta strandi550 – 5567
    Beta strandi561 – 5655
    Helixi568 – 5714
    Turni574 – 5774
    Beta strandi579 – 5813
    Beta strandi602 – 6043
    Beta strandi607 – 6093
    Helixi614 – 6174
    Helixi619 – 6213
    Beta strandi625 – 6339
    Beta strandi636 – 6449
    Helixi911 – 92313
    Turni924 – 9274
    Helixi931 – 94414
    Turni951 – 9533
    Helixi956 – 9583
    Helixi964 – 9674
    Turni971 – 9744
    Beta strandi975 – 9773
    Beta strandi982 – 9843
    Turni988 – 9903
    Beta strandi1000 – 10089
    Beta strandi1010 – 10134
    Turni1016 – 10183
    Helixi1019 – 10213
    Beta strandi1032 – 10354
    Helixi1039 – 104810
    Beta strandi1057 – 10637
    Beta strandi1068 – 10747
    Beta strandi1077 – 10815
    Helixi1082 – 10854
    Beta strandi1090 – 10923
    Beta strandi1095 – 10973
    Beta strandi1100 – 11034
    Turni1104 – 11074
    Beta strandi1108 – 11125
    Beta strandi1128 – 11336
    Beta strandi1139 – 11446
    Beta strandi1146 – 115712
    Helixi1158 – 11603
    Turni1161 – 11633
    Beta strandi1168 – 11703
    Turni1172 – 11743
    Beta strandi1176 – 118611
    Beta strandi1189 – 11979
    Helixi1198 – 12069
    Beta strandi1224 – 12263
    Turni1236 – 12383
    Helixi1239 – 12468
    Beta strandi1251 – 12566
    Helixi1258 – 127114
    Beta strandi1277 – 12804
    Beta strandi1283 – 12853
    Beta strandi1290 – 12956
    Helixi1296 – 13016
    Helixi1304 – 13074
    Beta strandi1311 – 13166
    Turni1317 – 13193
    Helixi1323 – 133513
    Turni1336 – 13405
    Beta strandi1342 – 13476
    Beta strandi1362 – 13665
    Beta strandi1371 – 13755
    Beta strandi1378 – 13803
    Helixi1382 – 13854
    Beta strandi1386 – 13938
    Helixi1397 – 140913
    Beta strandi1414 – 14174
    Helixi1423 – 14253
    Beta strandi1428 – 14369
    Beta strandi1442 – 14443
    Beta strandi1449 – 14535
    Beta strandi1456 – 14638
    Beta strandi1467 – 14693
    Beta strandi1471 – 14788
    Helixi1481 – 14888
    Beta strandi1493 – 14953
    Beta strandi1497 – 15026
    Helixi1514 – 152714
    Helixi1532 – 154413
    Beta strandi1545 – 15484
    Helixi1555 – 156410
    Helixi1570 – 15789
    Helixi1584 – 159714
    Helixi1606 – 16116
    Turni1614 – 16185
    Beta strandi1627 – 16293
    Beta strandi1635 – 16373
    Helixi1640 – 165213
    Beta strandi1680 – 16878
    Helixi1753 – 177725
    Helixi1940 – 196425
    Helixi1976 – 199924
    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
    Helixi2569 – 25713
    Beta strandi2579 – 25824
    Helixi2585 – 260723
    Helixi2608 – 26103
    Helixi2612 – 26143
    Helixi2617 – 262913
    Beta strandi2631 – 26399
    Helixi2644 – 26474
    Helixi2650 – 266011
    Helixi2667 – 267913
    Turni2680 – 26823
    Beta strandi2684 – 26874
    Beta strandi2693 – 26975
    Helixi2707 – 272620
    Beta strandi2729 – 27368
    Beta strandi2739 – 27457
    Helixi2749 – 276517
    Beta strandi2770 – 27723
    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 – 293418
    Helixi2936 – 294510
    Helixi2947 – 29493
    Beta strandi2950 – 29523
    Helixi2960 – 29645
    Turni2968 – 29714

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1A1RX-ray2.50A/B1027-1206[»]
    1A1VX-ray2.20A1193-1657[»]
    1CWXNMR-A2-45[»]
    1HEIX-ray2.10A/B1206-1656[»]
    1JR6NMR-A1353-1456[»]
    A1478-1507[»]
    1N1LX-ray2.60A/B1027-1206[»]
    1ONBNMR-A1353-1456[»]
    A1478-1507[»]
    1R7CNMR-A1973-2003[»]
    1R7DNMR-A1973-2003[»]
    1R7ENMR-A1973-2003[»]
    1R7FNMR-A1973-2003[»]
    1R7GNMR-A1973-2003[»]
    1RGQX-ray2.90A/B1027-1207[»]
    2A4RX-ray2.40A/C1027-1207[»]
    B/D1680-1696[»]
    2F9VX-ray2.60A/C1027-1207[»]
    B/D1678-1696[»]
    2HD0X-ray2.28A/B/C/D/E/F/G/H/I/J/K/L903-1026[»]
    2JXFNMR-A1751-1780[»]
    2KDRNMR-X1938-1965[»]
    2O8MX-ray2.00A/B1027-1207[»]
    C/D1678-1696[»]
    2OBOX-ray2.60A/C1022-1207[»]
    B/D1677-1695[»]
    2OBQX-ray2.50A/C1027-1207[»]
    B/D1678-1696[»]
    2OC0X-ray2.30A/C1027-1207[»]
    B/D1680-1696[»]
    2OC1X-ray2.70A/C1027-1207[»]
    B/D1680-1696[»]
    2OC7X-ray2.70A/C1027-1207[»]
    B/D1680-1696[»]
    2OC8X-ray2.66A/C1027-1207[»]
    B/D1680-1696[»]
    2OINX-ray2.50A/B1027-1207[»]
    C/D1678-1696[»]
    2P59X-ray2.90C/D1678-1696[»]
    2QV1X-ray2.40C/D1678-1696[»]
    2XI2X-ray1.80A/B/C2421-2990[»]
    2XI3X-ray1.70A/B2421-2990[»]
    2XNIX-ray3.30A/B1027-1206[»]
    4CL1X-ray3.50A/B/C/D2005-2174[»]
    4JZNX-ray2.05K434-446[»]
    4JZOX-ray2.22I/J/K/L434-446[»]
    4MWFX-ray2.64C/D412-459[»]
    C/D486-645[»]
    DisProtiDP00588.
    ProteinModelPortaliP27958.
    SMRiP27958. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27958.

    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 – 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
    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 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)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 – 237724V3Add
    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.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 NS3.1 Publication

    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: P27958-1) [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

    MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
    KTSERSQPRG RRQPIPKARR PEGRTWAQPG YPWPLYGNEG CGWAGWLLSP 100
    RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
    LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTVPAS AYQVRNSSGL 200
    YHVTNDCPNS SVVYEAADAI LHTPGCVPCV REGNASRCWV AVTPTVATRD 250
    GKLPTTQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRHHWT 300
    TQDCNCSIYP GHITGHRMAW NMMMNWSPTA ALVVAQLLRI PQAIMDMIAG 350
    AHWGVLAGIK YFSMVGNWAK VLVVLLLFAG VDAETHVTGG NAGRTTAGLV 400
    GLLTPGAKQN IQLINTNGSW HINSTALNCN ESLNTGWLAG LFYQHKFNSS 450
    GCPERLASCR RLTDFAQGWG PISYANGSGL DERPYCWHYP PRPCGIVPAK 500
    SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ANDTDVFVLN NTRPPLGNWF 550
    GCTWMNSTGF TKVCGAPPCV IGGVGNNTLL CPTDCFRKYP EATYSRCGSG 600
    PRITPRCMVD YPYRLWHYPC TINYTIFKVR MYVGGVEHRL EAACNWTRGE 650
    RCDLEDRDRS ELSPLLLSTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ 700
    YLYGVGSSIA SWAIKWEYVV LLFLLLADAR VCSCLWMMLL ISQAEAALEN 750
    LVILNAASLA GTHGLVSFLV FFCFAWYLKG RWVPGAVYAL YGMWPLLLLL 800
    LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS WCMWWLQYFL 850
    TRVEAQLHVW VPPLNVRGGR DAVILLTCVV HPALVFDITK LLLAIFGPLW 900
    ILQASLLKVP YFVRVQGLLR ICALARKIAG GHYVQMAIIK LGALTGTCVY 950
    NHLAPLRDWA HNGLRDLAVA VEPVVFSRME TKLITWGADT AACGDIINGL 1000
    PVSARRGQEI LLGPADGMVS KGWRLLAPIT AYAQQTRGLL GCIITSLTGR 1050
    DKNQVEGEVQ IVSTATQTFL ATCINGVCWT VYHGAGTRTI ASPKGPVIQT 1100
    YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI PVRRRGDSRG 1150
    SLLSPRPISY LKGSSGGPLL CPTGHAVGLF RAAVCTRGVA KAVDFIPVEN 1200
    LETTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAKGYK 1250
    VLVLNPSVAA TLGFGAYMSK AHGVDPNIRT GVRTITTGSP ITYSTYGKFL 1300
    ADAGCSGGAY DIIICDECHS TDATSISGIG TVLDQAETAG ARLVVLATAT 1350
    PPGSVTVSHP NIEEVALSTT GEIPFYGKAI PLEVIKGGRH LIFCHSKKKC 1400
    DELAAKLVAL GINAVAYYRG LDVSVIPTSG DVVVVSTDAL MTGFTGDFDS 1450
    VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRTQRRGR TGRGKPGIYR 1500
    FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV 1550
    CQDHLGFWEG VFTGLTHIDA HFLSQTKQSG ENFPYLVAYQ ATVCARAQAP 1600
    PPSWDQMRKC LIRLKPTLHG PTPLLYRLGA VQNEVTLTHP ITKYIMTCMS 1650
    ADLEVVTSTW VLVGGVLAAL AAYCLSTGCV VIVGRIVLSG KPAIIPDREV 1700
    LYQEFDEMEE CSQHLPYIEQ GMMLAEQFKQ KALGLLQTAS RHAEVITPAV 1750
    QTNWQKLEVF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTAAVTSP 1800
    LTTGQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAALD SVGLGKVLVD 1850
    ILAGYGAGVA GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALAVGVVFAS 1900
    ILRRRVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTAILSS 1950
    LTVTQLLRRL HQWISSECTT PCSGSWLRDI WDWICEVLSD FKTWLKAKLM 2000
    PQLPGIPFVS CQRGYRGVWR GDGIMHTRCH CGAEITGHVK NGTMRIVGPR 2050
    TCKNMWSGTF FINAYTTGPC TPLPAPNYKF ALWRVSAEEY VEIRRVGDFH 2100
    YVSGMTTDNL KCPCQIPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG 2150
    LHEYPVGSQL PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSMAS 2200
    SSASQLSAPS LKATCTANHD SPDAELIEAN LLWRQEMGGN ITRVESENKV 2250
    VILDSFDPLV AEEDEREVSV PAEILRKSRR FAPALPVWAR PDYNPLLVET 2300
    WKKPDYEPPV VHGCPLPPPR SPPVPPPRKK RTVVLTESTL PTALAELATK 2350
    SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DVESYSSMPP LEGEPGDPDL 2400
    SDGSWSTVSS GADTEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL 2450
    LRHHNLVYST TSRSACQRKK KVTFDRLQVL DSHYQDVLKE VKAAASKVKA 2500
    NLLSVEEACS LAPPHSAKSK FGYGAKDVRC HARKAVAHIN SVWKDLLEDS 2550
    VTPIDTTIMA KNEVFCVQPE KGGRKPARLI VFPDLGVRVC EKMALYDVVS 2600
    KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGLSYD TRCFDSTVTE 2650
    SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR 2700
    ASRVLTTSCG NTLTRYIKAR AACRAAGLQD CTMLVCGDDL VVICESAGVQ 2750
    EDAASLRAFT EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR 2800
    VYYLTRDPTT PLARAAWETA RHTPVNSWLG NIIMFAPTLW ARMILMTHFF 2850
    SVLIARDQLE QALNCEIYGA CYSIEPLDLP PIIQRLHGLS AFSLHSYSPG 2900
    EINRVAACLR KLGVPPLRAW RHRAWSVRAR LLARGGKAAI CGKYLFNWAV 2950
    RTKLKLTPIT AAGRLDLSGW FTAGYSGGDI YHSVSHARPR WFWFCLLLLA 3000
    AGVGIYLLPN R 3011

    Note: Produced by conventional translation.

    Length:3,011
    Mass (Da):327,146
    Last modified:January 23, 2007 - v3
    Checksum:i772CBB29CCD94753
    GO
    Isoform F protein (identifier: P0C045-1) [UniParc]FASTAAdd to Basket

    Also known as: Frameshifted protein

    The sequence of this isoform can be found in the external entry P0C045.
    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):17,006
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti212 – 2121V → I in strain: Isolate H77.
    Natural varianti297 – 2971H → R in strain: Isolate H77.
    Natural varianti303 – 3031D → S in strain: Isolate H77.
    Natural varianti321 – 3211N → D in strain: Isolate H77.
    Natural varianti360 – 3601K → A in strain: Isolate H77.
    Natural varianti391 – 3911N → S in strain: Isolate H77.
    Natural varianti394 – 3941R → H in strain: Isolate H77.
    Natural varianti431 – 4311E → D in strain: Isolate H77.
    Natural varianti434 – 4341N → T in strain: Isolate H77.
    Natural varianti444 – 4441Q → R in strain: Isolate H77.
    Natural varianti457 – 4571A → T in strain: Isolate H77.
    Natural varianti564 – 5663CGA → RGV in strain: Isolate H77.
    Natural varianti589 – 5891Y → H in strain: Isolate H77.
    Natural varianti602 – 6021R → W in strain: Isolate H77.
    Natural varianti650 – 6501E → G in strain: Isolate H77.
    Natural varianti773 – 7731C → R in strain: Isolate H77.
    Natural varianti787 – 7871V → A in strain: Isolate H77.
    Natural varianti790 – 7901L → F in strain: Isolate H77.
    Natural varianti877 – 8771T → M in strain: Isolate H77.
    Natural varianti883 – 8831A → T in strain: Isolate H77.
    Natural varianti948 – 9481C → Y in strain: Isolate H77.
    Natural varianti954 – 9541A → T in strain: Isolate H77.
    Natural varianti1026 – 10261L → Q in strain: Isolate H77.
    Natural varianti1033 – 10331A → T in strain: Isolate H77.
    Natural varianti1049 – 10491G → S in strain: Isolate H77.
    Natural varianti1100 – 11001T → M in strain: Isolate H77.
    Natural varianti1121 – 11211T → A in strain: Isolate H77.
    Natural varianti1173 – 11731T → A in strain: Isolate H77.
    Natural varianti1202 – 12021E → G in strain: Isolate H77.
    Natural varianti1214 – 12141S → P in strain: Isolate H77.
    Natural varianti1247 – 12471K → Q in strain: Isolate H77.
    Natural varianti1303 – 13031A → G in strain: Isolate H77.
    Natural varianti1327 – 13271S → L in strain: Isolate H77.
    Natural varianti1556 – 15561G → E in strain: Isolate H77.
    Natural varianti1608 – 16081R → W in strain: Isolate H77.
    Natural varianti1742 – 17421H → Q in strain: Isolate H77.
    Natural varianti1839 – 18402LD → IG in strain: Isolate H77.
    Natural varianti1893 – 18931A → V in strain: Isolate H77.
    Natural varianti1898 – 19003FAS → CAA in strain: Isolate H77.
    Natural varianti1905 – 19051R → H in strain: Isolate H77.
    Natural varianti1940 – 19401A → V in strain: Isolate H77.
    Natural varianti2043 – 20431T → A in strain: Isolate H77.
    Natural varianti2053 – 20531K → R in strain: Isolate H77.
    Natural varianti2061 – 20611F → L in strain: Isolate H77.
    Natural varianti2102 – 21021V → I in strain: Isolate H77.
    Natural varianti2185 – 21851A → E in strain: Isolate H77.
    Natural varianti2283 – 22831P → R in strain: Isolate H77.
    Natural varianti2296 – 22961L → P in strain: Isolate H77.
    Natural varianti2341 – 23411P → S in strain: Isolate H77.
    Natural varianti2355 – 23551S → P in strain: Isolate H77.
    Natural varianti2400 – 24001L → F in strain: Isolate H77.
    Natural varianti2425 – 24251S → T in strain: Isolate H77.
    Natural varianti2469 – 24691K → Q in strain: Isolate H77.
    Natural varianti2512 – 25121A → T in strain: Isolate H77.
    Natural varianti2637 – 26371L → F in strain: Isolate H77.
    Natural varianti2703 – 27031R → G in strain: Isolate H77.
    Natural varianti2715 – 27151R → C in strain: Isolate H77.
    Natural varianti2755 – 27551S → N in strain: Isolate H77.
    Natural varianti2925 – 29251W → R in strain: Isolate H77.
    Natural varianti2933 – 29331A → S in strain: Isolate H77.
    Natural varianti2937 – 29371K → R in strain: Isolate H77.
    Natural varianti2960 – 29601T → A in strain: Isolate H77.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M67463 Genomic RNA. Translation: AAA45534.1.
    AF009606 Genomic RNA. Translation: AAB66324.1.
    AF011751 Genomic RNA. Translation: AAB67036.1.
    AF011752 Genomic RNA. Translation: AAB67037.1.
    AF011753 Genomic RNA. Translation: AAB67038.1.
    PIRiA36814. GNWVCH.

    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
    M67463 Genomic RNA. Translation: AAA45534.1 .
    AF009606 Genomic RNA. Translation: AAB66324.1 .
    AF011751 Genomic RNA. Translation: AAB67036.1 .
    AF011752 Genomic RNA. Translation: AAB67037.1 .
    AF011753 Genomic RNA. Translation: AAB67038.1 .
    PIRi A36814. GNWVCH.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1A1R X-ray 2.50 A/B 1027-1206 [» ]
    1A1V X-ray 2.20 A 1193-1657 [» ]
    1CWX NMR - A 2-45 [» ]
    1HEI X-ray 2.10 A/B 1206-1656 [» ]
    1JR6 NMR - A 1353-1456 [» ]
    A 1478-1507 [» ]
    1N1L X-ray 2.60 A/B 1027-1206 [» ]
    1ONB NMR - A 1353-1456 [» ]
    A 1478-1507 [» ]
    1R7C NMR - A 1973-2003 [» ]
    1R7D NMR - A 1973-2003 [» ]
    1R7E NMR - A 1973-2003 [» ]
    1R7F NMR - A 1973-2003 [» ]
    1R7G NMR - A 1973-2003 [» ]
    1RGQ X-ray 2.90 A/B 1027-1207 [» ]
    2A4R X-ray 2.40 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    2F9V X-ray 2.60 A/C 1027-1207 [» ]
    B/D 1678-1696 [» ]
    2HD0 X-ray 2.28 A/B/C/D/E/F/G/H/I/J/K/L 903-1026 [» ]
    2JXF NMR - A 1751-1780 [» ]
    2KDR NMR - X 1938-1965 [» ]
    2O8M X-ray 2.00 A/B 1027-1207 [» ]
    C/D 1678-1696 [» ]
    2OBO X-ray 2.60 A/C 1022-1207 [» ]
    B/D 1677-1695 [» ]
    2OBQ X-ray 2.50 A/C 1027-1207 [» ]
    B/D 1678-1696 [» ]
    2OC0 X-ray 2.30 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    2OC1 X-ray 2.70 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    2OC7 X-ray 2.70 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    2OC8 X-ray 2.66 A/C 1027-1207 [» ]
    B/D 1680-1696 [» ]
    2OIN X-ray 2.50 A/B 1027-1207 [» ]
    C/D 1678-1696 [» ]
    2P59 X-ray 2.90 C/D 1678-1696 [» ]
    2QV1 X-ray 2.40 C/D 1678-1696 [» ]
    2XI2 X-ray 1.80 A/B/C 2421-2990 [» ]
    2XI3 X-ray 1.70 A/B 2421-2990 [» ]
    2XNI X-ray 3.30 A/B 1027-1206 [» ]
    4CL1 X-ray 3.50 A/B/C/D 2005-2174 [» ]
    4JZN X-ray 2.05 K 434-446 [» ]
    4JZO X-ray 2.22 I/J/K/L 434-446 [» ]
    4MWF X-ray 2.64 C/D 412-459 [» ]
    C/D 486-645 [» ]
    DisProti DP00588.
    ProteinModelPortali P27958.
    SMRi P27958. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P27958. 215 interactions.
    MINTi MINT-106294.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    euHCVdbi AF009606.
    AF011751.
    AF011752.
    AF011753.
    M67463.

    Miscellaneous databases

    EvolutionaryTracei P27958.

    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. "Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates."
      Inchauspe G., Zebedee S., Lee D.H.H., Sugitani M., Nasoff M., Prince A.M.
      Proc. Natl. Acad. Sci. U.S.A. 88:10292-10296(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], DOMAIN V3 REGION.
    2. "Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA."
      Kolykhalov A.A., Agapov E.V., Blight K.J., Mihalik K., Feinstone S.M., Rice C.M.
      Science 277:570-574(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate H77.
    3. "Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee."
      Yanagi M., Purcell R.H., Emerson S.U., Bukh J.
      Proc. Natl. Acad. Sci. U.S.A. 94:8738-8743(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate H77.
    4. Cited for: IDENTIFICATION OF THE CYSTEINE PROTEASE, MUTAGENESIS OF HIS-952; CYS-993 AND SER-1165.
    5. "Expression and identification of hepatitis C virus polyprotein cleavage products."
      Grakoui A., Wychowski C., Lin C., Feinstone S.M., Rice C.M.
      J. Virol. 67:1385-1395(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
    6. "Characterization of the nuclear localization signal and subcellular distribution of hepatitis C virus nonstructural protein NS5A."
      Ide Y., Zhang L., Chen M., Inchauspe G., Bahl C., Sasaguri Y., Padmanabhan R.
      Gene 182:203-211(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION OF NS5A, NUCLEAR LOCALIZATION SIGNAL.
    7. "Identification of the major phosphorylation site of the hepatitis C virus H strain NS5A protein as serine 2321."
      Reed K.E., Rice C.M.
      J. Biol. Chem. 274:28011-28018(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-2321, MUTAGENESIS OF SER-2321.
    8. "Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP."
      Ghosh A.K., Majumder M., Steele R., Yaciuk P., Chrivia J., Ray R., Ray R.B.
      J. Biol. Chem. 275:7184-7188(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF NS5A WITH SRCAP, SUBCELLULAR LOCATION OF NS5A.
    9. "Charged residues in the transmembrane domains of hepatitis C virus glycoproteins play a major role in the processing, subcellular localization, and assembly of these envelope proteins."
      Cocquerel L., Wychowski C., Minner F., Penin F., Dubuisson J.
      J. Virol. 74:3623-3633(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION OF E1 AND E2, ROLE OF TRANSMEMBRANE DOMAINS.
    10. "Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation."
      Kittlesen D.J., Chianese-Bullock K.A., Yao Z.Q., Braciale T.J., Hahn Y.S.
      J. Clin. Invest. 106:1239-1249(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF CORE PROTEIN WITH HUMAN C1QR1.
    11. "Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment."
      Penin F., Combet C., Germanidis G., Frainais P.-O., Deleage G., Pawlotsky J.-M.
      J. Virol. 75:5703-5710(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF HVR1 REGION.
    12. "Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase."
      Schmidt-Mende J., Bieck E., Huegle T., Penin F., Rice C.M., Blum H.E., Moradpour D.
      J. Biol. Chem. 276:44052-44063(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY OF NS5B.
    13. "Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins."
      Cocquerel L., Op de Beeck A., Lambot M., Roussel J., Delgrange D., Pillez A., Wychowski C., Penin F., Dubuisson J.
      EMBO J. 21:2893-2902(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY OF ENVELOPE GLYCOPROTEINS E1 AND E2.
    14. "Subcellular localization and topology of the p7 polypeptide of hepatitis C virus."
      Carrere-Kremer S., Montpellier-Pala C., Cocquerel L., Wychowski C., Penin F., Dubuisson J.
      J. Virol. 76:3720-3730(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY, SUBCELLULAR LOCATION OF P7.
    15. "An amino-terminal amphipathic alpha-helix mediates membrane association of the hepatitis C virus nonstructural protein 5A."
      Brass V., Bieck E., Montserret R., Woelk B., Hellings J.A., Blum H.E., Penin F., Moradpour D.
      J. Biol. Chem. 277:8130-8139(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY OF NS5A.
    16. "Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex."
      Egger D., Woelk B., Gosert R., Bianchi L., Blum H.E., Moradpour D., Bienz K.
      J. Virol. 76:5974-5984(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REPLICATION COMPLEX.
    17. "Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons."
      Gosert R., Egger D., Lohmann V., Bartenschlager R., Blum H.E., Bienz K., Moradpour D.
      J. Virol. 77:5487-5492(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REPLICATION COMPLEX.
    18. "The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives."
      Pavlovic D., Neville D.C., Argaud O., Blumberg B., Dwek R.A., Fischer W.B., Zitzmann N.
      Proc. Natl. Acad. Sci. U.S.A. 100:6104-6108(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION OF P7 BY LONG-ALKYL-CHAIN IMINOSUGAR DERIVATIVES.
    19. "The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences."
      Sakai A., Claire M.S., Faulk K., Govindarajan S., Emerson S.U., Purcell R.H., Bukh J.
      Proc. Natl. Acad. Sci. U.S.A. 100:11646-11651(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF LYS-779 AND ARG-781.
      Strain: Isolate H77.
    20. "Protein-protein interactions between hepatitis C virus nonstructural proteins."
      Dimitrova M., Imbert I., Kieny M.P., Schuster C.
      J. Virol. 77:5401-5414(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION BETWEEN NON-STRUCTURAL PROTEINS.
    21. "Topology of the membrane-associated hepatitis C virus protein NS4B."
      Lundin M., Monne M., Widell A., Von Heijne G., Persson M.A.A.
      J. Virol. 77:5428-5438(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY, SUBCELLULAR LOCATION OF NS4B.
      Strain: Isolate H77.
    22. "CD81-dependent binding of hepatitis C virus E1E2 heterodimers."
      Cocquerel L., Kuo C.-C., Dubuisson J., Levy S.
      J. Virol. 77:10677-10683(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81.
    23. "Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes."
      Bartosch B., Dubuisson J., Cosset F.-L.
      J. Exp. Med. 197:633-642(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81; LDLR AND SCARB1.
    24. "Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor."
      Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F.-L.
      J. Biol. Chem. 278:41624-41630(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81.
    25. "Characterization of functional hepatitis C virus envelope glycoproteins."
      Op De Beeck A., Voisset C., Bartosch B., Ciczora Y., Cocquerel L., Keck Z., Foung S., Cosset F.-L., Dubuisson J.
      J. Virol. 78:2994-3002(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF E1 AND E2.
    26. "Regulation of hepatitis C virus polyprotein processing by signal peptidase involves structural determinants at the p7 sequence junctions."
      Carrere-Kremer S., Montpellier C., Lorenzo L., Brulin B., Cocquerel L., Belouzard S., Penin F., Dubuisson J.
      J. Biol. Chem. 279:41384-41392(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
    27. "L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus."
      Cormier E.G., Durso R.J., Tsamis F., Boussemart L., Manix C., Olson W.C., Gardner J.P., Dragic T.
      Proc. Natl. Acad. Sci. U.S.A. 101:14067-14072(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CD209/DC-SIGN AND CLEC4M/DC-SIGNR.
      Strain: Isolate H77.
    28. "Analysis of the processing and transmembrane topology of the E2p7 protein of hepatitis C virus."
      Isherwood B.J., Patel A.H.
      J. Gen. Virol. 86:667-676(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CLEAVAGE BETWEEN E2 AND P7, TOPOLOGY OF P7, MUTAGENESIS OF VAL-720.
    29. "Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity."
      Li X.D., Sun L., Seth R.B., Pineda G., Chen Z.J.
      Proc. Natl. Acad. Sci. U.S.A. 102:17717-17722(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF NS3 PROTEASE WITH HUMAN MAVS.
    30. "Palmitoylation and polymerization or in protein-protein interactions of hepatitis C virus NS4B protein."
      Yu G.-Y., Lee K.-J., Gao L., Lai M.M.C.
      J. Virol. 80:6013-6023(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-1968 AND CYS-1972 (NS4B) BY HOST, MUTAGENESIS OF CYS-1968 AND CYS-1972.
      Strain: Isolate H77.
    31. "Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis."
      Codran A., Royer C., Jaeck D., Bastien-Valle M., Baumert T.F., Kieny M.P., Pereira C.A., Martin J.P.
      J. Gen. Virol. 87:2583-2593(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF E1 AND E2.
      Strain: Isolate H77.
    32. "The membrane-active regions of the hepatitis C virus E1 and E2 envelope glycoproteins."
      Perez-Berna A.J., Moreno M.R., Guillen J., Bernabeu A., Villalain J.
      Biochemistry 45:3755-3768(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF THE FUSION PEPTIDE.
      Strain: Isolate H77.
    33. "Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein."
      Lundin M., Lindstrom H., Groenwall C., Persson M.A.
      J. Gen. Virol. 87:3263-3272(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY OF NS4B.
      Strain: Isolate H77.
    34. "Molecular and structural characterization of the domain 2 of hepatitis C virus non-structural protein 5A."
      Liang Y., Kang C.B., Yoon H.S.
      Mol. Cells 22:13-20(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION OF NS5A WITH NS5B AND HOST PKR.
    35. "Conserved determinants for membrane association of nonstructural protein 5A from hepatitis C virus and related viruses."
      Brass V., Pal Z., Sapay N., Deleage G., Blum H.E., Penin F., Moradpour D.
      J. Virol. 81:2745-2757(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION OF NS5A.
    36. "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.
    37. "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.
    38. "Protein kinase C-related kinase 2 regulates hepatitis C virus RNA polymerase function by phosphorylation."
      Kim S.J., Kim J.H., Kim Y.G., Lim H.S., Oh J.W.
      J. Biol. Chem. 279:50031-50041(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, PHOSPHORYLATION, INTERACTION WITH PKN2.
    39. Cited for: REVIEW, SUBCELLULAR LOCATION.
    40. "Identification of a novel protein binding to hepatitis C virus core protein."
      Chen Y.R., Chen T.Y., Zhang S.L., Lin S.M., Zhao Y.R., Ye F., Zhang X., Shi L., Dang S.S., Liu M.
      J. Gastroenterol. Hepatol. 24:1300-1304(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ACY3.
    41. "Structure of the hepatitis C virus RNA helicase domain."
      Yao N., Hesson T., Cable M.B., Hong Z., Kwong A.D., Le H.V., Weber P.C.
      Nat. Struct. Biol. 4:463-467(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1206-1656.
    42. "Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide."
      Kim J.L., Morgenstern K.A., Lin C., Fox T., Dwyer M.D., Landro J.A., Chambers S.P., Markland W., Lepre C.A., O'Malley E.T., Harbeson S.L., Rice C.M., Murcko M.A., Caron P.R., Thomson J.A.
      Cell 87:343-355(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1027-1206 IN COMPLEX WITH NS4A.
    43. "Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding."
      Kim J.L., Morgenstern K.A., Griffith J.P., Dwyer M.D., Thomson J.A., Murcko M.A., Lin C., Caron P.R.
      Structure 6:89-100(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1192-1657.
    44. "Solution structure and backbone dynamics of an engineered arginine-rich subdomain 2 of the hepatitis C virus NS3 RNA helicase."
      Liu D., Wang Y.-S., Gesell J.J., Wyss D.F.
      J. Mol. Biol. 314:543-561(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1353-1507.
    45. "Pyrrolidine-5,5-trans-lactams. 2. The use of X-ray crystal structure data in the optimization of P3 and P4 substituents."
      Andrews D.M., Chaignot H., Coomber B.A., Good A.C., Hind S.L., Johnson M.R., Jones P.S., Mills G., Robinson J.E., Skarzynski T., Slater M.J., Somers D.O.
      Org. Lett. 4:4479-4482(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1027-1207.
    46. "Structure of the catalytic domain of the hepatitis C virus NS2-3 protease."
      Lorenz I.C., Marcotrigiano J., Dentzer T.G., Rice C.M.
      Nature 442:831-835(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 903-1026, MUTAGENESIS OF HIS-952 AND CYS-993.

    Entry informationi

    Entry nameiPOLG_HCVH
    AccessioniPrimary (citable) accession number: P27958
    Secondary accession number(s): O36579
    , O36608, O36609, O36610
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 168 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, Multifunctional enzyme, Reference proteome

    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