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P26662

- POLG_HCVJA

UniProt

P26662 - POLG_HCVJA

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Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1b (isolate Japanese) (HCV)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.3 Publications
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.3 Publications
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.3 Publications
Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation By similarity.3 Publications
NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS By similarity.3 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.3 Publications
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.3 Publications
NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication By similarity.3 Publications

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).
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.

Cofactori

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

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei177 – 1782Cleavage; by host signal peptidase By similarity
Sitei191 – 1922Cleavage; by host signal peptidase Reviewed prediction
Sitei383 – 3842Cleavage; by host signal peptidase Reviewed prediction
Sitei746 – 7472Cleavage; by host signal peptidase By similarity
Sitei809 – 8102Cleavage; by host signal peptidase By similarity
Active sitei952 – 9521For protease NS2-3 activity; shared with dimeric partner By similarity
Active sitei972 – 9721For protease NS2-3 activity; shared with dimeric partner By similarity
Active sitei993 – 9931For protease NS2-3 activity; shared with dimeric partner By similarity
Sitei1026 – 10272Cleavage; by protease NS2-3 Reviewed prediction
Active sitei1083 – 10831Charge relay system; for serine protease NS3 activity
Active sitei1107 – 11071Charge relay system; for serine protease NS3 activity
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 NS3 Reviewed prediction
Sitei1711 – 17122Cleavage; by serine protease NS3 Reviewed prediction
Sitei1972 – 19732Cleavage; by serine protease NS3 Reviewed prediction
Metal bindingi2011 – 20111Zinc By similarity
Metal bindingi2029 – 20291Zinc By similarity
Metal bindingi2031 – 20311Zinc By similarity
Metal bindingi2052 – 20521Zinc By similarity
Sitei2419 – 24202Cleavage; by serine protease NS3 Reviewed prediction

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1230 – 12378ATP Reviewed prediction

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. RNA helicase activity Source: CACAO
  9. serine-type endopeptidase activity Source: InterPro
  10. serine-type exopeptidase activity Source: InterPro
  11. structural molecule activity Source: InterPro
  12. zinc ion binding Source: InterPro

GO - Biological processi

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

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 Japanese) (HCV)
Taxonomic identifieri11116 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000008095: Genome

Subcellular locationi

Chain Core protein p21 : Host endoplasmic reticulum membrane; Single-pass membrane protein By similarity. Host mitochondrion membrane; 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.5 Publications
Chain Core protein p19 : Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity 5 Publications
Chain Envelope glycoprotein E1 : Virion membrane; Single-pass type I membrane protein Reviewed prediction. Host endoplasmic reticulum membrane; 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.5 Publications
Chain Envelope glycoprotein E2 : Virion membrane; Single-pass type I membrane protein Reviewed prediction. Host endoplasmic reticulum membrane; 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.5 Publications
Chain p7 : Host endoplasmic reticulum membrane; 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.5 Publications
Chain Protease NS2-3 : Host endoplasmic reticulum membrane; Multi-pass membrane protein Reviewed prediction 5 Publications
Chain Serine protease NS3 : Host endoplasmic reticulum membrane; Peripheral membrane protein By similarity
Note: NS3 is associated to the ER membrane through its binding to NS4A.5 Publications
Chain Non-structural protein 4A : Host endoplasmic reticulum membrane; Single-pass type I membrane protein Reviewed prediction
Note: Host membrane insertion occurs after processing by the NS3 protease.5 Publications
Chain Non-structural protein 4B : Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity 5 Publications
Chain Non-structural protein 5A : Host endoplasmic reticulum membrane; Peripheral membrane protein. Host cytoplasmhost perinuclear region. Host mitochondrion
Note: Host membrane insertion occurs after processing by the NS3 protease.5 Publications
Chain RNA-directed RNA polymerase : Host endoplasmic reticulum membrane; Single-pass type I membrane protein Reviewed prediction
Note: Host membrane insertion occurs after processing by the NS3 protease.5 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 168167Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei169 – 18921Helical; Reviewed predictionAdd
BLAST
Topological domaini190 – 358169Lumenal Reviewed predictionAdd
BLAST
Transmembranei359 – 37921Helical; Reviewed predictionAdd
BLAST
Topological domaini380 – 725346Lumenal Reviewed predictionAdd
BLAST
Transmembranei726 – 74621Helical; Reviewed predictionAdd
BLAST
Topological domaini747 – 75711Lumenal Reviewed predictionAdd
BLAST
Transmembranei758 – 77821Helical; Reviewed predictionAdd
BLAST
Topological domaini779 – 7824Cytoplasmic Reviewed prediction
Transmembranei783 – 80321Helical; Reviewed predictionAdd
BLAST
Topological domaini804 – 81310Lumenal Reviewed prediction
Transmembranei814 – 83421Helical; Reviewed predictionAdd
BLAST
Topological domaini835 – 88147Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei882 – 90221Helical; Reviewed predictionAdd
BLAST
Topological domaini903 – 92826Lumenal Reviewed predictionAdd
BLAST
Transmembranei929 – 94921Helical; Reviewed predictionAdd
BLAST
Topological domaini950 – 1657708Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1658 – 167821Helical; Reviewed predictionAdd
BLAST
Topological domaini1679 – 1805127Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1806 – 182621Helical; Reviewed predictionAdd
BLAST
Topological domaini1827 – 18282Lumenal Reviewed prediction
Transmembranei1829 – 184921Helical; Reviewed predictionAdd
BLAST
Topological domaini1850 – 18501Cytoplasmic Reviewed prediction
Transmembranei1851 – 187121Helical; Reviewed predictionAdd
BLAST
Topological domaini1872 – 188110Lumenal Reviewed prediction
Transmembranei1882 – 190221Helical; Reviewed predictionAdd
BLAST
Topological domaini1903 – 197270Cytoplasmic Reviewed predictionAdd
BLAST
Intramembranei1973 – 200230 By similarityAdd
BLAST
Topological domaini2003 – 2989987Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei2990 – 301021Helical; By similarityAdd
BLAST

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
Complete GO annotation...

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
Mutagenesisi139 – 1391L → A: Complete loss of core protein processing by host signal peptidase, no effect on the cleavage at core-E1 junction; when associated with A-140 and A-144. 1 Publication
Mutagenesisi140 – 1401V → A: Complete loss of core protein processing by host signal peptidase, no effect on the cleavage at core-E1 junction; when associated with A-139 and A-144. 1 Publication
Mutagenesisi144 – 1441L → A: Complete loss of core protein processing by host signal peptidase, no effect on the cleavage at core-E1 junction; when associated with A-139 and A-140. 1 Publication
Mutagenesisi176 – 1761I → A: Complete loss of core protein processing by host signal peptidase; when associated with L-177. 1 Publication
Mutagenesisi177 – 1771F → L: Complete loss of core protein processing by host signal peptidase; when associated with A-176. 1 Publication
Mutagenesisi178 – 1781L → V: No effect on processing of the core protein; when associated with V-179. 1 Publication
Mutagenesisi179 – 1791L → V: No effect on processing of the core protein; when associated with V-178. 1 Publication
Mutagenesisi181 – 1811L → V: No effect on processing of the core protein. 1 Publication
Mutagenesisi182 – 1821L → V: No effect on processing of the core protein. 1 Publication
Mutagenesisi183 – 1831S → L: No effect on processing of the core protein; when associated with A-184 or V-184. 1 Publication
Mutagenesisi184 – 1841C → A or V: No effect on processing of the core protein; when associated with L-183. 1 Publication
Mutagenesisi922 – 9221C → A: No effect on polyprotein processing. 1 Publication
Mutagenesisi932 – 9321H → A: No effect on polyprotein processing. 1 Publication
Mutagenesisi952 – 9521H → A or R: Complete loss of protease NS2-3 activity. 1 Publication
Mutagenesisi972 – 9721E → Q: Reduced protease NS2-3 activity. 1 Publication
Mutagenesisi980 – 9801E → Q: No effect on polyprotein processing. 1 Publication
Mutagenesisi993 – 9931C → A: Complete loss of protease NS2-3 activity. 1 Publication
Mutagenesisi1009 – 10091E → Q: No effect on polyprotein processing. 1 Publication
Mutagenesisi1042 – 10421C → A: No effect on zinc-binding by serine protease NS3. 1 Publication
Mutagenesisi1058 – 10581E → Q: No effect on polyprotein processing. 1 Publication
Mutagenesisi1073 – 10731C → S: No effect on zinc-binding by serine protease NS3. 1 Publication
Mutagenesisi1078 – 10781C → L: No effect on zinc-binding by serine protease NS3. 1 Publication
Mutagenesisi1083 – 10831H → A: Complete loss of serine protease NS3 activity. No effect on zinc-binding by serine protease NS3. 3 Publications
Mutagenesisi1107 – 11071D → A: Complete loss of serine protease NS3 activity. 2 Publications
Mutagenesisi1123 – 11231C → A: Reduced protease NS2-3 and serine protease NS3 activities. 1 Publication
Mutagenesisi1125 – 11251C → A: Reduced protease NS2-3 and serine protease NS3 activities. 1 Publication
Mutagenesisi1136 – 11361H → A: No effect on polyprotein processing. No effect on zinc-binding by serine protease NS3. 2 Publications
Mutagenesisi1165 – 11651S → A: Complete loss of serine protease NS3 activity. No effect on zinc-binding by serine protease NS3. 3 Publications
Mutagenesisi1171 – 11711C → A: Reduced protease NS2-3 and serine protease NS3 activities. 1 Publication
Mutagenesisi1175 – 11751H → A: No effect on polyprotein processing. Reduces zinc-binding by serine protease NS3. 2 Publications
Mutagenesisi1185 – 11851C → A: No effect on polyprotein processing. No effect on zinc-binding by serine protease NS3. 2 Publications
Mutagenesisi1199 – 11991E → Q: No effect on polyprotein processing. 1 Publication
Mutagenesisi1202 – 12021E → Q: No effect on polyprotein processing. 1 Publication
Mutagenesisi1227 – 12271H → A: No effect on polyprotein processing. No effect on zinc-binding by serine protease NS3. 2 Publications
Mutagenesisi1229 – 12291H → A: No effect on polyprotein processing. No effect on zinc-binding by serine protease NS3. 2 Publications
Mutagenesisi2194 – 21941S → A: No effect on NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2197 – 21971S → A: Loss of NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2200 – 22001S → A: No effect on NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2201 – 22011S → A: Loss of NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2202 – 22021S → A: No effect on NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2204 – 22041S → A: Loss of NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2207 – 22071S → A: No effect on NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2210 – 22101S → A: No effect on NS5A hyperphosphorylation. 1 Publication
Mutagenesisi2221 – 22211S → A: No effect on NS5A hyperphosphorylation. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed; by host By similarity
Chaini2 – 191190Core protein p21 Reviewed predictionPRO_0000037637Add
BLAST
Chaini2 – 177176Core protein p19 By similarityPRO_0000037638Add
BLAST
Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarityPRO_0000037639Add
BLAST
Chaini192 – 383192Envelope glycoprotein E1 Reviewed predictionPRO_0000037640Add
BLAST
Chaini384 – 746363Envelope glycoprotein E2 Reviewed predictionPRO_0000037641Add
BLAST
Chaini747 – 80963p7 By similarityPRO_0000037642Add
BLAST
Chaini810 – 1026217Protease NS2-3 Reviewed predictionPRO_0000037643Add
BLAST
Chaini1027 – 1657631Serine protease NS3 Reviewed predictionPRO_0000037644Add
BLAST
Chaini1658 – 171154Non-structural protein 4A Reviewed predictionPRO_0000037645Add
BLAST
Chaini1712 – 1972261Non-structural protein 4B Reviewed predictionPRO_0000037646Add
BLAST
Chaini1973 – 2419447Non-structural protein 5A Reviewed predictionPRO_0000037647Add
BLAST
Chaini2420 – 3010591RNA-directed RNA polymerase Reviewed predictionPRO_0000037648Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine; by host By similarity
Modified residuei53 – 531Phosphoserine; by host By similarity
Modified residuei99 – 991Phosphoserine; by host By similarity
Modified residuei116 – 1161Phosphoserine; by host PKA By similarity
Glycosylationi196 – 1961N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi209 – 2091N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi234 – 2341N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi250 – 2501N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi305 – 3051N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi417 – 4171N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi423 – 4231N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi430 – 4301N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi448 – 4481N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi532 – 5321N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi556 – 5561N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi576 – 5761N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi623 – 6231N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi645 – 6451N-linked (GlcNAc...); by host Reviewed prediction
Lipidationi1968 – 19681S-palmitoyl cysteine; by host By similarity
Lipidationi1972 – 19721S-palmitoyl cysteine; by host By similarity
Disulfide bondi2114 ↔ 2162 By similarity
Modified residuei2194 – 21941Phosphoserine; by host; in p56
Modified residuei2197 – 21971Phosphoserine; by host; in p58
Modified residuei2201 – 22011Phosphoserine; by host; in p58
Modified residuei2204 – 22041Phosphoserine; by host; in p58

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.2 Publications
Envelope E1 and E2 glycoproteins are highly N-glycosylated By similarity.
Core protein is phosphorylated by host PKC and PKA By similarity.1 Publication
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.1 Publication
NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions 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.
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 transcription. In addition to blocking the formation of phosphorylated STAT1, the core protein also promotes ubiquitin-mediated proteasome-dependent degradation of STAT1. Interacts 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.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAXQ078123EBI-9099462,EBI-516580From a different organism.
GRB2P629933EBI-9099462,EBI-401755From a different organism.

Protein-protein interaction databases

IntActiP26662. 5 interactions.
MINTiMINT-6803641.

Structurei

Secondary structure

1
3010
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi786 – 80116
Beta strandi1030 – 10356
Helixi1039 – 104810
Beta strandi1057 – 10637
Beta strandi1068 – 10747
Beta strandi1077 – 10804
Helixi1082 – 10854
Beta strandi1090 – 10923
Beta strandi1095 – 10973
Beta strandi1100 – 11034
Turni1104 – 11074
Beta strandi1108 – 11125
Beta strandi1128 – 11336
Beta strandi1139 – 11446
Beta strandi1146 – 115712
Helixi1158 – 11614
Beta strandi1168 – 11703
Beta strandi1176 – 118611
Beta strandi1189 – 11979
Helixi1198 – 12069
Beta strandi1680 – 168910

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DXPX-ray2.40A/B1027-1213[»]
C/D1678-1691[»]
1DY8X-ray2.40A/B1027-1213[»]
C/D1678-1692[»]
1DY9X-ray2.10A/B1027-1213[»]
C/D1678-1692[»]
1W3CX-ray2.30A/B1027-1213[»]
C/D1678-1692[»]
2K8JNMR-X781-809[»]
3OYPX-ray2.76A/B1027-1213[»]
C/D1678-1691[»]
3P8NX-ray1.90A/B1027-1206[»]
C/D1678-1691[»]
3P8OX-ray2.30A/B1027-1206[»]
C/D1678-1691[»]
4A1TX-ray2.05A/B1028-1206[»]
A/B1678-1690[»]
4A1VX-ray2.20A/B1028-1206[»]
A/B1678-1690[»]
4A1XX-ray1.90A/B1028-1206[»]
4I31X-ray1.93A/B1027-1206[»]
C/D1678-1691[»]
4I32X-ray2.30A/B1027-1206[»]
C/D1678-1691[»]
4I33X-ray1.90A/B1027-1206[»]
C/D1678-1691[»]
4JMYX-ray1.95C/D1678-1691[»]
4KTCX-ray2.30A/C1028-1213[»]
ProteinModelPortaliP26662.
SMRiP26662. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2985.

Miscellaneous databases

EvolutionaryTraceiP26662.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini903 – 1026124Peptidase C18Add
BLAST
Domaini1217 – 1369153Helicase ATP-bindingAdd
BLAST
Domaini2633 – 2751119RdRp catalyticAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 5958Interaction with DDX3X By similarityAdd
BLAST
Regioni2 – 2322Interaction with STAT1Add
BLAST
Regioni122 – 17352Interaction with APOA2 By similarityAdd
BLAST
Regioni150 – 15910Mitochondrial targeting signal By similarity
Regioni164 – 1674Important for lipid droplets localization By similarity
Regioni265 – 29632Fusion peptide Reviewed predictionAdd
BLAST
Regioni385 – 41127HVR1 By similarityAdd
BLAST
Regioni475 – 4817HVR2 By similarity
Regioni482 – 49413CD81-binding 1 Reviewed predictionAdd
BLAST
Regioni522 – 55332CD81-binding 2 Reviewed predictionAdd
BLAST
Regioni660 – 67112PKR/eIF2-alpha phosphorylation homology domain (PePHD)Add
BLAST
Regioni1679 – 169012NS3-binding (by NS4A) Reviewed predictionAdd
BLAST
Regioni2120 – 2332213Transcriptional activation Reviewed predictionAdd
BLAST
Regioni2120 – 220889FKBP8-binding Reviewed predictionAdd
BLAST
Regioni2200 – 225051Basal phosphorylationAdd
BLAST
Regioni2210 – 227566PKR-binding Reviewed predictionAdd
BLAST
Regioni2210 – 224940ISDR By similarityAdd
BLAST
Regioni2249 – 230658NS4B-binding Reviewed predictionAdd
BLAST
Regioni2351 – 241969Basal phosphorylationAdd
BLAST
Regioni2354 – 237724V3 By similarityAdd
BLAST

Motif

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi796 – 8038Poly-Leu
Compositional biasi1432 – 14354Poly-Val
Compositional biasi2282 – 232746Pro-richAdd
BLAST
Compositional biasi2993 – 29986Poly-Leu

Domaini

The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2). E2 also contain two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2 and CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy By similarity.1 Publication
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.1 Publication
The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases By similarity.1 Publication
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

Keywords - Domaini

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.

P26662-1 [UniParc]FASTAAdd to Basket

« Hide

MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
KTSERSQPRG RRQPIPKARR PEGRTWAQPG YPWPLYGNEG MGWAGWLLSP 100
RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTIPAS AYEVRNVSGI 200
YHVTNDCSNS SIVYEAADMI MHTPGCVPCV RESNFSRCWV ALTPTLAARN 250
SSIPTTTIRR HVDLLVGAAA LCSAMYVGDL CGSVFLVSQL FTFSPRRYET 300
VQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG 350
AHWGVLAGLA YYSMVGNWAK VLIVMLLFAG VDGHTHVTGG RVASSTQSLV 400
SWLSQGPSQK IQLVNTNGSW HINRTALNCN DSLQTGFIAA LFYAHRFNAS 450
GCPERMASCR PIDEFAQGWG PITHDMPESS DQRPYCWHYA PRPCGIVPAS 500
QVCGPVYCFT PSPVVVGTTD RFGAPTYSWG ENETDVLLLS NTRPPQGNWF 550
GCTWMNSTGF TKTCGGPPCN IGGVGNNTLV CPTDCFRKHP EATYTKCGSG 600
PWLTPRCMVD YPYRLWHYPC TVNFTVFKVR MYVGGVEHRL NAACNWTRGE 650
RCDLEDRDRS ELSPLLLSTT EWQILPCSFT TLPALSTGLI HLHRNIVDVQ 700
YLYGIGSAVV SFAIKWEYIL LLFLLLADAR VCACLWMMLL IAQAEATLEN 750
LVVLNAASVA GAHGLLSFLV FFCAAWYIKG RLVPGAAYAL YGVWPLLLLL 800
LALPPRAYAM DREMAASCGG AVFVGLVLLT LSPYYKVFLA RLIWWLQYFI 850
TRAEAHLQVW VPPLNVRGGR DAIILLTCAV HPELIFDITK LLLAILGPLM 900
VLQAGITRVP YFVRAQGLIR ACMLVRKVAG GHYVQMAFMK LAALTGTYVY 950
DHLTPLRDWA HAGLRDLAVA VEPVVFSDME TKLITWGADT AACGDIISGL 1000
PVSARRGKEI LLGPADSFGE QGWRLLAPIT AYSQQTRGLL GCIITSLTGR 1050
DKNQVDGEVQ VLSTATQSFL ATCVNGVCWT VYHGAGSKTL AGPKGPITQM 1100
YTNVDQDLVG WPAPPGARSM TPCTCGSSDL YLVTRHADVV PVRRRGDSRG 1150
SLLSPRPISY LKGSSGGPLL CPSGHVVGIF RAAVCTRGVA KAVDFIPVES 1200
METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK 1250
VLVLNPSVAA TLGFGAYMSK AHGIEPNIRT GVRTITTGGP ITYSTYCKFL 1300
ADGGCSGGAY DIIICDECHS TDSTTILGIG TVLDQAETAG ARLVVLATAT 1350
PPGSITVPHP NIEEVALSNT GEIPFYGKAI PIEAIKGGRH LIFCHSKKKC 1400
DELAAKLTGL GLNAVAYYRG LDVSVIPTSG DVVVVATDAL MTGFTGDFDS 1450
VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRAQRRGR TGRGRSGIYR 1500
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV 1550
CQDHLEFWES VFTGLTHIDA HFLSQTKQAG DNLPYLVAYQ ATVCARAQAP 1600
PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEVTLTHP ITKYIMACMS 1650
ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV VIVGRIILSG RPAVIPDREV 1700
LYQEFDEMEE CASHLPYIEQ GMQLAEQFKQ KALGLLQTAT KQAEAAAPVV 1750
ESKWRALEVF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP 1800
LTTQNTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD 1850
ILAGYGAGVA GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA 1900
ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTQILSS 1950
LTITQLLKRL HQWINEDCST PCSGSWLKDV WDWICTVLSD FKTWLQSKLL 2000
PRLPGLPFLS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK NGSMRIVGPK 2050
TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH 2100
YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPVCKPL LREEVVFQVG 2150
LNQYLVGSQL PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS 2200
SSASQLSAPS LKATCTTHHD SPDADLIEAN LLWRQEMGGN ITRVESENKV 2250
VILDSFDPIR AVEDEREISV PAEILRKPRK FPPALPIWAR PDYNPPLLES 2300
WKDPDYVPPV VHGCPLPSTK APPIPPPRRK RTVVLTESTV SSALAELATK 2350
TFGSSGSSAV DSGTATGPPD QASDDGDKGS DVESYSSMPP LEGEPGDPDL 2400
SDGSWSTVSG EAGEDVVCCS MSYTWTGALI TPCAAEESKL PINPLSNSLL 2450
RHHSMVYSTT SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAR 2500
LLSIEEACKL TPPHSAKSKF GYGAKDVRSL SSRAVNHIRS VWEDLLEDTE 2550
TPIDTTIMAK NEVFCVQPEK GGRKPARLIV FPDLGVRVCE KMALYDVVST 2600
LPQAVMGPSY GFQYSPGQRV EFLVNTWKSK KCPMGFSYDT RCFDSTVTEN 2650
DIRTEESIYQ CCDLAPEARQ AIRSLTERLY VGGPLTNSKG QNCGYRRCRA 2700
SGVLTTSCGN TLTCYLKATA ACRAAKLQDC TMLVNGDDLV VICESAGTQE 2750
DAAALRAFTE AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV 2800
YYLTRDPTTP LARAAWETVR HTPVNSWLGN IIMYAPTLWA RMILMTHFFS 2850
ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ IIERLHGLSA FSLHSYSPGE 2900
INRVASCLRK LGVPPLRVWR HRARSVRAKL LSQGGRAATC GKYLFNWAVK 2950
TKLKLTPIPA ASQLDLSGWF VAGYNGGDIY HSLSRARPRW FMLCLLLLSV 3000
GVGIYLLPNR 3010
Length:3,010
Mass (Da):327,021
Last modified:January 23, 2007 - v3
Checksum:iAA993794F46DB185
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti464 – 4641E → K.
Natural varianti475 – 4795DMPES → VVPNI.
Natural varianti492 – 4921R → Q.
Natural varianti522 – 5243FGA → SGV.
Natural varianti538 – 5403LLS → VLN.
Natural varianti580 – 5801V → I.
Natural varianti608 – 6081M → L.
Natural varianti622 – 6221V → I.
Natural varianti626 – 6261V → I.
Natural varianti674 – 6741I → V.
Natural varianti694 – 6941R → Q.
Natural varianti705 – 7051I → V.
Natural varianti708 – 7081A → V.
Natural varianti712 – 7132FA → VV.
Natural varianti719 – 7191I → V.
Natural varianti906 – 9061I → M.
Natural varianti983 – 9831L → I.
Natural varianti1140 – 11401V → I.
Natural varianti1158 – 11581I → V.
Natural varianti1252 – 12521L → R.
Natural varianti1297 – 12971C → G.
Natural varianti1323 – 13231S → W.
Natural varianti1477 – 14771L → V.
Natural varianti1485 – 14851A → S.
Natural varianti1536 – 15361S → T.
Natural varianti1583 – 15831L → F.
Natural varianti1635 – 16351V → I.
Natural varianti1644 – 16452YI → FV.
Natural varianti1695 – 16951I → V.
Natural varianti1703 – 17031Q → R.
Natural varianti1710 – 17101E → A.
Natural varianti1713 – 17131S → P.
Natural varianti1753 – 17531K → R.
Natural varianti1759 – 17591V → A.
Natural varianti1839 – 18391V → I.
Natural varianti1873 – 18731M → A.
Natural varianti1876 – 18761T → A.
Natural varianti1896 – 18961V → I.
Natural varianti1978 – 19781K → R.
Natural varianti1989 – 19891S → T.
Natural varianti2002 – 20021R → K.
Natural varianti2006 – 20061L → V.
Natural varianti2009 – 20091L → F.
Natural varianti2093 – 20931V → I.
Natural varianti2125 – 21251V → L.
Natural varianti2136 – 21383VCK → ACR.
Natural varianti2143 – 21464EEVV → VDVT.
Natural varianti2190 – 21901L → P.
Natural varianti2196 – 21961P → S.
Natural varianti2199 – 21991A → G.
Natural varianti2199 – 21991A → V.
Natural varianti2200 – 22001S → T.
Natural varianti2204 – 22041S → R.
Natural varianti2205 – 22051Q → H.
Natural varianti2208 – 22081A → T.
Natural varianti2209 – 22091P → H.
Natural varianti2209 – 22091P → L.
Natural varianti2209 – 22091P → S.
Natural varianti2210 – 22101S → P.
Natural varianti2211 – 22111L → S.
Natural varianti2212 – 22121K → E.
Natural varianti2212 – 22121K → R.
Natural varianti2214 – 22141T → A.
Natural varianti2215 – 22151C → Y.
Natural varianti2216 – 22161T → I.
Natural varianti2217 – 22171T → A.
Natural varianti2218 – 22181H → A.
Natural varianti2218 – 22181H → L.
Natural varianti2218 – 22181H → Q.
Natural varianti2218 – 22181H → R.
Natural varianti2218 – 22181H → T.
Natural varianti2219 – 22191H → R.
Natural varianti2219 – 22191H → Y.
Natural varianti2220 – 22201D → G.
Natural varianti2222 – 22221P → L.
Natural varianti2222 – 22221P → S.
Natural varianti2223 – 22231D → G.
Natural varianti2224 – 22241A → V.
Natural varianti2225 – 22251D → G.
Natural varianti2225 – 22251D → N.
Natural varianti2227 – 22271I → V.
Natural varianti2228 – 22281E → A.
Natural varianti2228 – 22281E → D.
Natural varianti2228 – 22281E → G.
Natural varianti2228 – 22281E → K.
Natural varianti2230 – 22301N → D.
Natural varianti2230 – 22301N → S.
Natural varianti2233 – 22331W → R.
Natural varianti2259 – 22591I → L.
Natural varianti2262 – 22621V → E.
Natural varianti2268 – 22681I → V.
Natural varianti2271 – 22711P → A.
Natural varianti2278 – 22792PR → SK.
Natural varianti2303 – 23031D → S.
Natural varianti2310 – 23101V → A.
Natural varianti2318 – 23214STKA → PTTG.
Natural varianti2329 – 23291R → K.
Natural varianti2367 – 23671G → A.
Natural varianti2372 – 23721A → T.
Natural varianti2379 – 23791G → E.
Natural varianti2382 – 23821V → I.
Natural varianti2414 – 24163EDV → DDI.
Natural varianti2673 – 26731R → K.
Natural varianti2681 – 26811V → I.
Natural varianti2754 – 27541A → S.
Natural varianti2757 – 27571A → V.
Natural varianti2950 – 29501K → R.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D90208 Genomic RNA. Translation: BAA14233.1.
D89872 Genomic RNA. Translation: BAA14035.1.
D11397 Genomic RNA. Translation: BAA20975.1.
PIRiA39253. GNWVCJ.

Cross-referencesi

Web resourcesi

euHCVdb

The European HCV database

Virus Pathogen Resource

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D90208 Genomic RNA. Translation: BAA14233.1 .
D89872 Genomic RNA. Translation: BAA14035.1 .
D11397 Genomic RNA. Translation: BAA20975.1 .
PIRi A39253. GNWVCJ.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1DXP X-ray 2.40 A/B 1027-1213 [» ]
C/D 1678-1691 [» ]
1DY8 X-ray 2.40 A/B 1027-1213 [» ]
C/D 1678-1692 [» ]
1DY9 X-ray 2.10 A/B 1027-1213 [» ]
C/D 1678-1692 [» ]
1W3C X-ray 2.30 A/B 1027-1213 [» ]
C/D 1678-1692 [» ]
2K8J NMR - X 781-809 [» ]
3OYP X-ray 2.76 A/B 1027-1213 [» ]
C/D 1678-1691 [» ]
3P8N X-ray 1.90 A/B 1027-1206 [» ]
C/D 1678-1691 [» ]
3P8O X-ray 2.30 A/B 1027-1206 [» ]
C/D 1678-1691 [» ]
4A1T X-ray 2.05 A/B 1028-1206 [» ]
A/B 1678-1690 [» ]
4A1V X-ray 2.20 A/B 1028-1206 [» ]
A/B 1678-1690 [» ]
4A1X X-ray 1.90 A/B 1028-1206 [» ]
4I31 X-ray 1.93 A/B 1027-1206 [» ]
C/D 1678-1691 [» ]
4I32 X-ray 2.30 A/B 1027-1206 [» ]
C/D 1678-1691 [» ]
4I33 X-ray 1.90 A/B 1027-1206 [» ]
C/D 1678-1691 [» ]
4JMY X-ray 1.95 C/D 1678-1691 [» ]
4KTC X-ray 2.30 A/C 1028-1213 [» ]
ProteinModelPortali P26662.
SMRi P26662. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2985.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P26662. 5 interactions.
MINTi MINT-6803641.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

euHCVdbi D89872.
D90208.

Miscellaneous databases

EvolutionaryTracei P26662.

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. "Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis."
    Kato N., Hijikata M., Ootsuyama Y., Nakagawa M., Ohkoshi S., Sugimura T., Shimotohno K.
    Proc. Natl. Acad. Sci. U.S.A. 87:9524-9528(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Molecular structure of the Japanese hepatitis C viral genome."
    Kato N., Hijikata M., Nakagawa M., Ootsuyama Y., Muraiso K., Ohkoshi S., Shimotohno K.
    FEBS Lett. 280:325-328(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISCUSSION OF SEQUENCE.
  3. Tanaka T.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus."
    Hijikata M., Mizushima H., Akagi T., Mori S., Kakiuchi N., Kato N., Tanaka T., Kimura K., Shimotohno K.
    J. Virol. 67:4665-4675(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 723-1908, IDENTIFICATION OF BOTH PROTEASES, MUTAGENESIS OF CYS-922; HIS-932; HIS-952; GLU-972; GLU-980; CYS-993; GLU-1009; GLU-1058; HIS-1083; ASP-1107; CYS-1123; CYS-1125; HIS-1136; SER-1165; CYS-1171; HIS-1175; CYS-1185; GLU-1199; GLU-1202; HIS-1227 AND HIS-1229.
  5. "Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells."
    Shih C.-M., Lo S.J., Miyamura T., Chen S.-Y., Lee Y.-H.W.
    J. Virol. 67:5823-5832(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION OF HEPATITIS B VIRUS GENE EXPRESSION.
  6. "Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions."
    Bartenschlager R., Ahlborn-Laake L., Mous J., Jacobsen H.
    J. Virol. 67:3835-3844(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF HIS-1083; ASP-1107 AND SER-1165, IDENTIFICATION OF THE SERINE PROTEASE.
  7. "Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome."
    Kaneko T., Tanji Y., Satoh S., Hijikata M., Asabe S., Kimura K., Shimotohno K.
    Biochem. Biophys. Res. Commun. 205:320-326(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION OF NS5A.
  8. "Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A."
    Tanji Y., Kaneko T., Satoh S., Shimotohno K.
    J. Virol. 69:3980-3986(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-2194; SER-2197; SER-2200; SER-2201; SER-2202; SER-2204; SER-2207; SER-2210 AND SER-2221.
  9. "Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection."
    Enomoto N., Sakuma I., Asahina Y., Kurosaki M., Murakami T., Yamamoto C., Ogura Y., Izumi N., Marumo F., Sato C.
    N. Engl. J. Med. 334:77-81(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF NS5A.
  10. "Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator."
    Kato N., Lan K.H., Ono-Nita S.K., Shiratori Y., Omata M.
    J. Virol. 71:8856-8859(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF NS5A.
  11. "The NS3 proteinase domain of hepatitis C virus is a zinc-containing enzyme."
    Stempniak M., Hostomska Z., Nodes B.R., Hostomsky Z.
    J. Virol. 71:2881-2886(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: ZINC-BINDING REGION (SERINE PROTEASE NS3), COFACTOR (SERINE PROTEASE NS3), MUTAGENESIS OF CYS-1042; CYS-1073; CYS-1078; HIS-1083; HIS-1136; SER-1165; HIS-1175; CYS-1185; HIS-1227 AND HIS-1229.
  12. "The native form and maturation process of hepatitis C virus core protein."
    Yasui K., Wakita T., Tsukiyama-Kohara K., Funahashi S., Ichikawa M., Kajita T., Moradpour D., Wands J.R., Kohara M.
    J. Virol. 72:6048-6055(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN.
  13. "Interferon resistance of hepatitis C virus genotype 1b: relationship to nonstructural 5A gene quasispecies mutations."
    Pawlotsky J.-M., Germanidis G., Neumann A.U., Pellerin M., Frainais P.-O., Dhumeaux D.
    J. Virol. 72:2795-2805(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN ISDR REGION.
  14. "Cleavage of hepatitis C virus nonstructural protein 5A by a caspase-like protease(s) in mammalian cells."
    Satoh S., Hirota M., Noguchi T., Hijikata M., Handa H., Shimotohno K.
    Virology 270:476-487(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF NS5A.
  15. "Oligomerization and cooperative RNA synthesis activity of hepatitis C virus RNA-dependent RNA polymerase."
    Wang Q.M., Hockman M.A., Staschke K., Johnson R.B., Case K.A., Lu J., Parsons S., Zhang F., Rathnachalam R., Kirkegaard K., Colacino J.M.
    J. Virol. 76:3865-3872(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: OLIGOMERIZATION OF NS5B.
  16. "The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine."
    Griffin S.D., Beales L.P., Clarke D.S., Worsfold O., Evans S.D., Jaeger J., Harris M.P., Rowlands D.J.
    FEBS Lett. 535:34-38(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION OF P7 BY AMANTADINE.
  17. "Modulation of retinoid signaling by a cytoplasmic viral protein via sequestration of Sp110b, a potent transcriptional corepressor of retinoic acid receptor, from the nucleus."
    Watashi K., Hijikata M., Tagawa A., Doi T., Marusawa H., Shimotohno K.
    Mol. Cell. Biol. 23:7498-7509(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF CORE PROTEIN WITH HUMAN SP110.
  18. "Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein."
    Okamoto K., Moriishi K., Miyamura T., Matsuura Y.
    J. Virol. 78:6370-6380(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE OF CORE PROTEIN BY THE SIGNAL PEPTIDASE, MUTAGENESIS OF LEU-139; VAL-140; LEU-144; ILE-176; PHE-177; LEU-178; LEU-179; LEU-181; LEU-182; SER-183 AND CYS-184.
  19. "Hepatitis C virus core protein acts as a trans-modulating factor on internal translation initiation of the viral RNA."
    Boni S., Lavergne J.-P., Boulant S., Cahour A.
    J. Biol. Chem. 280:17737-17748(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  20. "Hepatitis C virus expression suppresses interferon signaling by degrading STAT1."
    Lin W., Choe W.H., Hiasa Y., Kamegaya Y., Blackard J.T., Schmidt E.V., Chung R.T.
    Gastroenterology 128:1034-1041(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF CORE PROTEIN WITH HUMAN STAT1.
  21. "Molecular determinants for subcellular localization of hepatitis C virus core protein."
    Suzuki R., Sakamoto S., Tsutsumi T., Rikimaru A., Tanaka K., Shimoike T., Moriishi K., Iwasaki T., Mizumoto K., Matsuura Y., Miyamura T., Suzuki T.
    J. Virol. 79:1271-1281(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN.
  22. "Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein."
    Huang L., Hwang J., Sharma S.D., Hargittai M.R., Chen Y., Arnold J.J., Raney K.D., Cameron C.E.
    J. Biol. Chem. 280:36417-36428(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF NS5A.
  23. "Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B."
    Hamamoto I., Nishimura Y., Okamoto T., Aizaki H., Liu M., Mori Y., Abe T., Suzuki T., Lai M.M., Miyamura T., Moriishi K., Matsuura Y.
    J. Virol. 79:13473-13482(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF NS5A AND NS5B WITH HUMAN VAPB.
  24. "Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain."
    Lin W., Kim S.S., Yeung E., Kamegaya Y., Blackard J.T., Kim K.A., Holtzman M.J., Chung R.T.
    J. Virol. 80:9226-9235(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF CORE PROTEIN WITH HUMAN STAT1.
  25. "Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells."
    Wang J., Tong W., Zhang X., Chen L., Yi Z., Pan T., Hu Y., Xiang L., Yuan Z.
    FEBS Lett. 580:4392-4400(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF NS5A WITH HUMAN FKBP8, SUBCELLULAR LOCATION OF NS5A.
  26. "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.
  27. Cited for: REVIEW, SUBCELLULAR LOCATION.
  28. "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.
  29. "Inhibition of the hepatitis C virus NS3/4A protease. The crystal structures of two protease-inhibitor complexes."
    Di Marco S., Rizzi M., Volpari C., Walsh M.A., Narjes F., Colarusso S., De Francesco R., Matassa V.G., Sollazzo M.
    J. Biol. Chem. 275:7152-7157(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1027-1213.
  30. "The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease."
    Ontoria J.M., Di Marco S., Conte I., Di Francesco M.E., Gardelli C., Koch U., Matassa V.G., Poma M., Steinkuehler C., Volpari C., Harper S.
    J. Med. Chem. 47:6443-6446(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1027-1213 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.

Entry informationi

Entry nameiPOLG_HCVJA
AccessioniPrimary (citable) accession number: P26662
Secondary accession number(s): P89966, Q81755
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 155 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.
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.

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.

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

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