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Q9WMX2

- POLG_HCVCO

UniProt

Q9WMX2 - POLG_HCVCO

Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1b (isolate Con1) (HCV)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (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. 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 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 the host antiviral protein MAVS By similarity. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state.By similarity2 Publications
    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.2 Publications

    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 peptidaseBy similarity
    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 – 20111Zinc1 Publication
    Metal bindingi2029 – 20291Zinc1 Publication
    Metal bindingi2031 – 20311Zinc1 Publication
    Metal bindingi2052 – 20521Zinc1 Publication
    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. RNA binding Source: UniProtKB-KW
    7. RNA-directed RNA polymerase activity Source: UniProtKB-KW
    8. serine-type endopeptidase activity Source: InterPro
    9. serine-type exopeptidase activity Source: InterPro
    10. structural molecule activity Source: InterPro
    11. zinc ion binding Source: InterPro

    GO - Biological processi

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

    Keywords - Molecular functioni

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

    Keywords - Biological processi

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

    Keywords - Ligandi

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

    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 (isolate Con1) (HCV)
    Taxonomic identifieri333284 [NCBI]
    Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000007414: Genome

    Subcellular locationi

    Chain Core protein p21 : Host endoplasmic reticulum membrane By similarity; Single-pass membrane protein By similarity. Host mitochondrion membrane By similarity; Single-pass type I membrane protein By similarity. Host lipid droplet By similarity
    Note: The C-terminal transmembrane domain of core protein p21 contains an ER signal leading the nascent polyprotein to the ER membrane. Only a minor proportion of core protein is present in the nucleus and an unknown proportion is secreted.
    Chain Core protein p19 : Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity
    Chain Envelope glycoprotein E1 : Virion membrane Curated; Single-pass type I membrane protein Curated. Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
    Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E1 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
    Chain Envelope glycoprotein E2 : Virion membrane Curated; Single-pass type I membrane protein Curated. Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
    Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E2 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
    Chain p7 : Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity. Host cell membrane By similarity
    Note: The C-terminus of p7 membrane domain acts as a signal sequence. After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. Only a fraction localizes to the plasma membrane.
    Chain Serine protease NS3 : Host endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
    Note: NS3 is associated to the ER membrane through its binding to NS4A.
    Chain Non-structural protein 4A : Host endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated
    Note: Host membrane insertion occurs after processing by the NS3 protease.
    Chain Non-structural protein 5A : Host endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity. Host cytoplasmhost perinuclear region By similarity. Host mitochondrion By similarity
    Note: Host membrane insertion occurs after processing by the NS3 protease.
    Chain RNA-directed RNA polymerase : Host endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated
    Note: Host membrane insertion occurs after processing by the NS3 protease.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2158 – 21581S → A: No effect on replication. 1 Publication
    Mutagenesisi2173 – 21731S → A: No effect on replication. 1 Publication
    Mutagenesisi2179 – 21791S → A: No effect on replication. 1 Publication
    Mutagenesisi2194 – 21941S → A: No effect on replication. No effect on NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2194 – 21941S → E: No effect on replication. No effect on NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2197 – 21971S → A: Enhanced replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2197 – 21971S → E: No effect on replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2200 – 22001S → A: No effect on replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2200 – 22001S → E: No effect on replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2201 – 22011S → A: Enhanced replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2201 – 22011S → E: Enhanced replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2202 – 22021S → A: Enhanced replication.No effect on NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2202 – 22021S → E: No effect on replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2204 – 22041S → A: Enhanced replication. Decreased NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2204 – 22041S → E: No effect on replication. No effect on NS5A hyperphosphorylation. 1 Publication
    Mutagenesisi2207 – 22071S → A: Enhanced replication. No effect on hyperphosphorylation. 1 Publication
    Mutagenesisi2207 – 22071S → E: No effect on replication. 1 Publication
    Mutagenesisi2210 – 22101S → A: No effect on replication. No effect on hyperphosphorylation. 1 Publication
    Mutagenesisi2210 – 22101S → E: No effect on replication. No effect on hyperphosphorylation. 1 Publication
    Mutagenesisi2221 – 22211S → A: No effect on hyperphosphorylation.
    Mutagenesisi2246 – 22461S → A: No effect on replication. 1 Publication
    Mutagenesisi2255 – 22551S → A: No effect on replication. 1 Publication
    Mutagenesisi2269 – 22691S → A: No effect on replication. 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_0000037541Add
    BLAST
    Chaini2 – 177176Core protein p19By similarityPRO_0000037542Add
    BLAST
    Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityPRO_0000037543Add
    BLAST
    Chaini192 – 383192Envelope glycoprotein E1Sequence AnalysisPRO_0000037544Add
    BLAST
    Chaini384 – 746363Envelope glycoprotein E2Sequence AnalysisPRO_0000037545Add
    BLAST
    Chaini747 – 80963p7By similarityPRO_0000037546Add
    BLAST
    Chaini810 – 1026217Protease NS2-3PROSITE-ProRule annotationPRO_0000037547Add
    BLAST
    Chaini1027 – 1657631Serine protease NS3Sequence AnalysisPRO_0000037548Add
    BLAST
    Chaini1658 – 171154Non-structural protein 4ASequence AnalysisPRO_0000037549Add
    BLAST
    Chaini1712 – 1972261Non-structural protein 4BSequence AnalysisPRO_0000037550Add
    BLAST
    Chaini1973 – 2419447Non-structural protein 5ASequence AnalysisPRO_0000037551Add
    BLAST
    Chaini2420 – 3010591RNA-directed RNA polymeraseSequence AnalysisPRO_0000037552Add
    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
    Glycosylationi532 – 5321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi556 – 5561N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi576 – 5761N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi623 – 6231N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi645 – 6451N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi1968 – 19681S-palmitoyl cysteine; by hostBy similarity
    Lipidationi1972 – 19721S-palmitoyl cysteine; by hostBy similarity
    Disulfide bondi2114 ↔ 21621 Publication
    Modified residuei2194 – 21941Phosphoserine; by host; in p562 Publications
    Modified residuei2197 – 21971Phosphoserine; by host; in p582 Publications
    Modified residuei2201 – 22011Phosphoserine; by host; in p582 Publications
    Modified residuei2204 – 22041Phosphoserine; by host; in p582 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.By similarity
    Core protein is phosphorylated by host PKC and PKA.By similarity
    NS5A is phosphorylated in a basal form termed p56. p58 is a hyperphosphorylated form of p56. p56 and p58 coexist in the cell in roughly equivalent amounts. Hyperphosphorylation is dependent on the presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6 and CSNK1A1/CKI-alpha kinases may be responsible for NS5A phosphorylation By similarity.By similarity
    NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions By similarity.By similarity
    The N-terminus of a fraction of NS4B molecules seems to be relocated post-translationally from the cytoplasm to the ER lumen, with a 5th transmembrane segment. The C-terminus of NS2 may be lumenal with a fourth transmembrane segment By similarity.By similarity
    Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity

    Keywords - PTMi

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

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    P266635EBI-6863741,EBI-6874437From a different organism.
    BCKDKO148742EBI-6863741,EBI-1046765From a different organism.
    BIN1O004994EBI-6863748,EBI-719094From a different organism.
    CALCOCO2Q131373EBI-6863741,EBI-739580From a different organism.
    CEP85Q6P2H32EBI-6863741,EBI-2808308From a different organism.
    EFEMP1Q128052EBI-6863748,EBI-536772From a different organism.
    EIF4ENIF1Q9NRA83EBI-6863741,EBI-301024From a different organism.
    FKBP8Q143188EBI-6863748,EBI-724839From a different organism.
    FLNAP213336EBI-6863741,EBI-350432From a different organism.
    FRS3O435593EBI-6863741,EBI-725515From a different organism.
    FYNP062412EBI-710918,EBI-515315From a different organism.
    GBP2P324562EBI-6863741,EBI-714388From a different organism.
    GOLGA2Q083792EBI-6863748,EBI-618309From a different organism.
    GPS2Q132272EBI-6863748,EBI-713355From a different organism.
    ITGALP207012EBI-6863748,EBI-961214From a different organism.
    KPNA1P522942EBI-6863741,EBI-358383From a different organism.
    LYNP079483EBI-710918,EBI-79452From a different organism.
    MOB1AQ9H8S92EBI-6863748,EBI-748229From a different organism.
    NAP1L2Q9ULW62EBI-6863748,EBI-3911716From a different organism.
    NR4A1P227362EBI-9028517,EBI-721550From a different organism.
    PKMP146184EBI-710918,EBI-353408From a different organism.
    PLIN3O606645EBI-6863748,EBI-725795From a different organism.
    PLSCR1O151628EBI-710918,EBI-740019From a different organism.
    PPP1R13LQ8WUF52EBI-6863748,EBI-5550163From a different organism.
    PSMB9P280652EBI-6863748,EBI-603300From a different organism.
    PTPLAD1Q9P0353EBI-6863748,EBI-359013From a different organism.
    RASAL2Q9UJF22EBI-6863741,EBI-359444From a different organism.
    SMURF2Q9HAU42EBI-6863741,EBI-396727From a different organism.
    SORBS2O948752EBI-6863748,EBI-311323From a different organism.
    TXNDC11Q6PKC32EBI-6863748,EBI-749812From a different organism.
    VPS52Q8N1B42EBI-6863748,EBI-2799833From a different organism.

    Protein-protein interaction databases

    IntActiQ9WMX2. 363 interactions.
    MINTiMINT-6548770.

    Structurei

    Secondary structure

    1
    3010
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi843 – 85715
    Helixi873 – 8797
    Helixi882 – 89413
    Helixi898 – 9014
    Turni902 – 9054
    Beta strandi1224 – 12296
    Turni1236 – 12383
    Helixi1239 – 12468
    Beta strandi1251 – 12566
    Helixi1258 – 127114
    Beta strandi1277 – 12793
    Beta strandi1290 – 12956
    Helixi1296 – 13016
    Beta strandi1311 – 13155
    Turni1316 – 13194
    Helixi1323 – 133513
    Turni1336 – 13405
    Beta strandi1342 – 13509
    Beta strandi1362 – 13665
    Beta strandi1371 – 13755
    Beta strandi1378 – 13803
    Helixi1382 – 13843
    Beta strandi1386 – 13938
    Helixi1397 – 140913
    Beta strandi1414 – 14174
    Helixi1423 – 14253
    Beta strandi1428 – 14369
    Helixi1438 – 14403
    Beta strandi1441 – 14433
    Beta strandi1448 – 14536
    Beta strandi1456 – 14638
    Beta strandi1467 – 14693
    Beta strandi1471 – 14788
    Helixi1481 – 14888
    Beta strandi1493 – 14953
    Beta strandi1497 – 15037
    Beta strandi1509 – 15113
    Helixi1514 – 152613
    Helixi1532 – 154312
    Helixi1555 – 15639
    Helixi1570 – 157910
    Helixi1584 – 159714
    Helixi1606 – 161712
    Beta strandi1626 – 16294
    Helixi1640 – 16489
    Beta strandi1680 – 168910
    Turni2007 – 20093
    Beta strandi2017 – 20215
    Beta strandi2023 – 20286
    Beta strandi2034 – 20407
    Beta strandi2043 – 20475
    Helixi2053 – 20575
    Beta strandi2067 – 20693
    Beta strandi2071 – 20733
    Beta strandi2079 – 20868
    Beta strandi2089 – 20968
    Beta strandi2099 – 21079
    Helixi2119 – 21213
    Beta strandi2123 – 21253
    Beta strandi2146 – 21494
    Beta strandi2152 – 21554
    Beta strandi2421 – 24255
    Helixi2444 – 24474
    Helixi2453 – 24553
    Beta strandi2456 – 24583
    Helixi2461 – 24633
    Helixi2464 – 24718
    Helixi2481 – 249414
    Helixi2504 – 25096
    Turni2519 – 25213
    Helixi2524 – 25285
    Helixi2532 – 254716
    Beta strandi2549 – 25513
    Beta strandi2555 – 25595
    Beta strandi2563 – 25653
    Beta strandi2569 – 25713
    Beta strandi2578 – 25814
    Helixi2584 – 260623
    Helixi2607 – 26093
    Helixi2611 – 26133
    Helixi2616 – 262914
    Beta strandi2630 – 264011
    Helixi2643 – 26464
    Helixi2649 – 265911
    Helixi2666 – 267813
    Turni2679 – 26813
    Beta strandi2683 – 26864
    Beta strandi2688 – 26903
    Beta strandi2692 – 26965
    Helixi2706 – 272520
    Beta strandi2728 – 27358
    Beta strandi2738 – 27447
    Helixi2748 – 276417
    Beta strandi2769 – 27713
    Beta strandi2776 – 27783
    Helixi2779 – 27813
    Beta strandi2787 – 27937
    Beta strandi2799 – 28046
    Helixi2808 – 281912
    Helixi2826 – 28338
    Turni2834 – 28363
    Helixi2838 – 28425
    Helixi2844 – 285512
    Beta strandi2858 – 28603
    Beta strandi2862 – 28665
    Beta strandi2869 – 28735
    Helixi2875 – 28773
    Helixi2878 – 28869
    Helixi2888 – 28914
    Helixi2898 – 291114
    Helixi2916 – 293217
    Helixi2935 – 294410
    Helixi2946 – 29483
    Beta strandi2949 – 29513
    Helixi2959 – 29635
    Turni2967 – 29704
    Turni2974 – 29763
    Beta strandi2980 – 29823
    Beta strandi2984 – 29874

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ZH1X-ray2.50A/B2008-2170[»]
    2JY0NMR-A810-836[»]
    2KWTNMR-A836-868[»]
    2KWZNMR-A869-908[»]
    3FQLX-ray1.80A2421-2989[»]
    3FQMX-ray1.90A/B2005-2174[»]
    3FQQX-ray2.20A/B2005-2174[»]
    3KN2X-ray2.30B/D1678-1696[»]
    3KQHX-ray2.40A/B1215-1650[»]
    3KQKX-ray2.80A/B1215-1650[»]
    3KQLX-ray2.50A/B1215-1650[»]
    3KQNX-ray2.05A1215-1650[»]
    3KQUX-ray2.40A/B/C/D/E/F1215-1650[»]
    3Q0ZX-ray2.29A/B2420-2992[»]
    3QGDX-ray2.60A/B2420-2992[»]
    3QGEX-ray3.00A/B2420-2992[»]
    3QGFX-ray2.45A/B2420-2992[»]
    3QGGX-ray3.22A/B2420-2992[»]
    4NLDX-ray2.75A2420-2992[»]
    DisProtiDP00615.
    ProteinModelPortaliQ9WMX2.
    SMRiQ9WMX2. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2982.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9WMX2.

    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 biasi2282 – 232746Pro-richAdd
    BLAST
    Compositional biasi2718 – 27214Poly-Ala
    Compositional biasi2995 – 29984Poly-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 contains a variable region called interferon sensitivity determining region (ISDR) and 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). ISDR and V3 may be involved in sensitivity and/or resistance to IFN-alpha therapy 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.

    Q9WMX2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
    KTSERSQPRG RRQPIPKARQ PEGRAWAQPG YPWPLYGNEG LGWAGWLLSP 100
    RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
    LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTIPAS AYEVRNVSGV 200
    YHVTNDCSNA SIVYEAADMI MHTPGCVPCV RENNSSRCWV ALTPTLAARN 250
    ASVPTTTIRR HVDLLVGAAA LCSAMYVGDL CGSVFLVAQL FTFSPRRHET 300
    VQDCNCSIYP GHVTGHRMAW DMMMNWSPTA ALVVSQLLRI PQAVVDMVAG 350
    AHWGVLAGLA YYSMVGNWAK VLIVMLLFAG VDGGTYVTGG TMAKNTLGIT 400
    SLFSPGSSQK IQLVNTNGSW HINRTALNCN DSLNTGFLAA LFYVHKFNSS 450
    GCPERMASCS PIDAFAQGWG PITYNESHSS DQRPYCWHYA PRPCGIVPAA 500
    QVCGPVYCFT PSPVVVGTTD RFGVPTYSWG ENETDVLLLN NTRPPQGNWF 550
    GCTWMNSTGF TKTCGGPPCN IGGIGNKTLT CPTDCFRKHP EATYTKCGSG 600
    PWLTPRCLVH YPYRLWHYPC TVNFTIFKVR MYVGGVEHRL EAACNWTRGE 650
    RCNLEDRDRS ELSPLLLSTT EWQVLPCSFT TLPALSTGLI HLHQNVVDVQ 700
    YLYGIGSAVV SFAIKWEYVL LLFLLLADAR VCACLWMMLL IAQAEAALEN 750
    LVVLNAASVA GAHGILSFLV FFCAAWYIKG RLVPGAAYAL YGVWPLLLLL 800
    LALPPRAYAM DREMAASCGG AVFVGLILLT LSPHYKLFLA RLIWWLQYFI 850
    TRAEAHLQVW IPPLNVRGGR DAVILLTCAI HPELIFTITK ILLAILGPLM 900
    VLQAGITKVP YFVRAHGLIR ACMLVRKVAG GHYVQMALMK LAALTGTYVY 950
    DHLTPLRDWA HAGLRDLAVA VEPVVFSDME TKVITWGADT AACGDIILGL 1000
    PVSARRGREI HLGPADSLEG QGWRLLAPIT AYSQQTRGLL GCIITSLTGR 1050
    DRNQVEGEVQ VVSTATQSFL ATCVNGVCWT VYHGAGSKTL AGPKGPITQM 1100
    YTNVDQDLVG WQAPPGARSL TPCTCGSSDL YLVTRHADVI PVRRRGDSRG 1150
    SLLSPRPVSY LKGSSGGPLL CPSGHAVGIF RAAVCTRGVA KAVDFVPVES 1200
    METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK 1250
    VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGAP ITYSTYGKFL 1300
    ADGGCSGGAY DIIICDECHS TDSTTILGIG TVLDQAETAG ARLVVLATAT 1350
    PPGSVTVPHP NIEEVALSST GEIPFYGKAI PIETIKGGRH LIFCHSKKKC 1400
    DELAAKLSGL GLNAVAYYRG LDVSVIPTSG DVIVVATDAL MTGFTGDFDS 1450
    VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRMGIYR 1500
    FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV 1550
    CQDHLEFWES VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP 1600
    PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEVTTTHP ITKYIMACMS 1650
    ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV VIVGRIILSG KPAIIPDREV 1700
    LYREFDEMEE CASHLPYIEQ GMQLAEQFKQ KAIGLLQTAT KQAEAAAPVV 1750
    ESKWRTLEAF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP 1800
    LTTQHTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD 1850
    ILAGYGAGVA GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA 1900
    ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTQILSS 1950
    LTITQLLKRL HQWINEDCST PCSGSWLRDV WDWICTVLTD FKTWLQSKLL 2000
    PRLPGVPFFS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK NGSMRIVGPR 2050
    TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH 2100
    YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPACKPL LREEVTFLVG 2150
    LNQYLVGSQL PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS 2200
    SSASQLSAPS LKATCTTRHD SPDADLIEAN LLWRQEMGGN ITRVESENKV 2250
    VILDSFEPLQ AEEDEREVSV PAEILRRSRK FPRAMPIWAR PDYNPPLLES 2300
    WKDPDYVPPV VHGCPLPPAK APPIPPPRRK RTVVLSESTV SSALAELATK 2350
    TFGSSESSAV DSGTATASPD QPSDDGDAGS DVESYSSMPP LEGEPGDPDL 2400
    SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEETKL PINALSNSLL 2450
    RHHNLVYATT SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK 2500
    LLSVEEACKL TPPHSARSKF GYGAKDVRNL SSKAVNHIRS VWKDLLEDTE 2550
    TPIDTTIMAK NEVFCVQPEK GGRKPARLIV FPDLGVRVCE KMALYDVVST 2600
    LPQAVMGSSY GFQYSPGQRV EFLVNAWKAK KCPMGFAYDT RCFDSTVTEN 2650
    DIRVEESIYQ CCDLAPEARQ AIRSLTERLY IGGPLTNSKG QNCGYRRCRA 2700
    SGVLTTSCGN TLTCYLKAAA ACRAAKLQDC TMLVCGDDLV VICESAGTQE 2750
    DEASLRAFTE AMTRYSAPPG DPPKPEYDLE LITSCSSNVS VAHDASGKRV 2800
    YYLTRDPTTP LARAAWETAR HTPVNSWLGN IIMYAPTLWA RMILMTHFFS 2850
    ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ IIQRLHGLSA FSLHSYSPGE 2900
    INRVASCLRK LGVPPLRVWR HRARSVRARL LSQGGRAATC GKYLFNWAVR 2950
    TKLKLTPIPA ASQLDLSSWF VAGYSGGDIY HSLSRARPRW FMWCLLLLSV 3000
    GVGIYLLPNR 3010
    Length:3,010
    Mass (Da):326,906
    Last modified:January 23, 2007 - v3
    Checksum:i37B3448DAFA9A10B
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2204 – 22041S → I.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ238799 Genomic RNA. Translation: CAB46677.1.
    PIRiA61196.
    PQ0246.
    PS0329.

    Cross-referencesi

    Web resourcesi

    euHCVdb

    The European HCV database

    HCV database

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ238799 Genomic RNA. Translation: CAB46677.1 .
    PIRi A61196.
    PQ0246.
    PS0329.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ZH1 X-ray 2.50 A/B 2008-2170 [» ]
    2JY0 NMR - A 810-836 [» ]
    2KWT NMR - A 836-868 [» ]
    2KWZ NMR - A 869-908 [» ]
    3FQL X-ray 1.80 A 2421-2989 [» ]
    3FQM X-ray 1.90 A/B 2005-2174 [» ]
    3FQQ X-ray 2.20 A/B 2005-2174 [» ]
    3KN2 X-ray 2.30 B/D 1678-1696 [» ]
    3KQH X-ray 2.40 A/B 1215-1650 [» ]
    3KQK X-ray 2.80 A/B 1215-1650 [» ]
    3KQL X-ray 2.50 A/B 1215-1650 [» ]
    3KQN X-ray 2.05 A 1215-1650 [» ]
    3KQU X-ray 2.40 A/B/C/D/E/F 1215-1650 [» ]
    3Q0Z X-ray 2.29 A/B 2420-2992 [» ]
    3QGD X-ray 2.60 A/B 2420-2992 [» ]
    3QGE X-ray 3.00 A/B 2420-2992 [» ]
    3QGF X-ray 2.45 A/B 2420-2992 [» ]
    3QGG X-ray 3.22 A/B 2420-2992 [» ]
    4NLD X-ray 2.75 A 2420-2992 [» ]
    DisProti DP00615.
    ProteinModelPortali Q9WMX2.
    SMRi Q9WMX2. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2982.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9WMX2. 363 interactions.
    MINTi MINT-6548770.

    Chemistry

    BindingDBi Q9WMX2.
    ChEMBLi CHEMBL5536.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    euHCVdbi AJ238799.

    Miscellaneous databases

    EvolutionaryTracei Q9WMX2.

    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. "Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line."
      Lohmann V., Koerner F., Koch J.O., Herian U., Theilmann L., Bartenschlager R.
      Science 285:110-113(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease."
      Foy E., Li K., Wang C., Sumpter R. Jr., Ikeda M., Lemon S.M., Gale M. Jr.
      Science 300:1145-1148(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF NS3 AND NS4A.
    3. "Reduction of hepatitis C virus NS5A hyperphosphorylation by selective inhibition of cellular kinases activates viral RNA replication in cell culture."
      Neddermann P., Quintavalle M., Di Pietro C., Clementi A., Cerretani M., Altamura S., Bartholomew L., De Francesco R.
      J. Virol. 78:13306-13314(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF NS5A.
    4. "Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain."
      Appel N., Pietschmann T., Bartenschlager R.
      J. Virol. 79:3187-3194(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-2194; SER-2197; SER-2201 AND SER-2204, MUTAGENESIS OF SER-2158; SER-2173; SER-2179; SER-2194; SER-2197; SER-2200; SER-2201; SER-2202; SER-2204; SER-2207; SER-2210; SER-2246; SER-2255 AND SER-2269.
    5. "Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses."
      Otsuka M., Kato N., Moriyama M., Taniguchi H., Wang Y., Dharel N., Kawabe T., Omata M.
      Hepatology 41:1004-1012(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN TBK1.
    6. "The alpha isoform of protein kinase CKI is responsible for hepatitis C virus NS5A hyperphosphorylation."
      Quintavalle M., Sambucini S., Di Pietro C., De Francesco R., Neddermann P.
      J. Virol. 80:11305-11312(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY HOST CSNK1A1.
      Strain: Isolate HCV-AT.
    7. "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.
    8. Cited for: REVIEW, SUBCELLULAR LOCATION.
    9. "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.
    10. "Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase."
      Tellinghuisen T.L., Marcotrigiano J., Rice C.M.
      Nature 435:374-379(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2008-2170, DISULFIDE BOND, COFACTOR (NS5A).
    11. "Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus."
      Love R.A., Brodsky O., Hickey M.J., Wells P.A., Cronin C.N.
      J. Virol. 83:4395-4403(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2005-2174 IN COMPLEX WITH ZINC, COFACTOR (NS5A).

    Entry informationi

    Entry nameiPOLG_HCVCO
    AccessioniPrimary (citable) accession number: Q9WMX2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 129 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

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

    Caution

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

    Keywords - Technical termi

    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