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P26664

- POLG_HCV1

UniProt

P26664 - POLG_HCV1

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Protein
Genome polyprotein
Gene
N/A
Organism
Hepatitis C virus genotype 1a (isolate 1) (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.7 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.7 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.7 Publications
Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation.7 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.7 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.7 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 By similarity.7 Publications
NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication By similarity.7 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 By similarity.
Binds 1 zinc ion per NS5A N-terminal domain By similarity.

Enzyme regulationi

Activity of auto-protease NS2-3 is dependent on zinc ions and completely inhibited by EDTA. Serine protease NS3 is also activated by zinc ions By similarity.

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 By similarity
Active sitei1107 – 11071Charge relay system; for serine protease NS3 activity By similarity
Metal bindingi1123 – 11231Zinc By similarity
Metal bindingi1125 – 11251Zinc By similarity
Active sitei1165 – 11651Charge relay system; for serine protease NS3 activity By similarity
Metal bindingi1171 – 11711Zinc By similarity
Metal bindingi1175 – 11751Zinc By similarity
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
Sitei2420 – 24212Cleavage; 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. RNA binding Source: UniProtKB-KW
  4. RNA-directed RNA polymerase activity Source: UniProtKB-KW
  5. cysteine-type endopeptidase activity Source: InterPro
  6. ion channel activity Source: UniProtKB-KW
  7. protein binding Source: UniProtKB
  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
Complete GO annotation...

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

Enzyme and pathway databases

SABIO-RKP26664.

Protein family/group databases

MEROPSiC18.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 11 chains:
Alternative name(s):
Capsid protein C
p21
Alternative name(s):
gp32
gp35
Alternative name(s):
NS1
gp68
gp70
Protease NS2-3 (EC:3.4.22.-)
Short name:
p23
Alternative name(s):
Hepacivirin
NS3P
p70
Alternative name(s):
p8
Alternative name(s):
p27
Alternative name(s):
p56
Alternative name(s):
NS5B
p68
OrganismiHepatitis C virus genotype 1a (isolate 1) (HCV)
Taxonomic identifieri11104 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007410: Genome, UP000008855: Genome

Subcellular locationi

Chain Core protein p21 : Host endoplasmic reticulum membrane; Single-pass membrane protein. Host mitochondrion membrane; Single-pass type I membrane protein. Host lipid droplet
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.3 Publications
Chain Core protein p19 : Virion. Host cytoplasm. Host nucleus. Secreted 3 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.3 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.3 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.3 Publications
Chain Protease NS2-3 : Host endoplasmic reticulum membrane; Multi-pass membrane protein Reviewed prediction 3 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.3 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.3 Publications
Chain Non-structural protein 4B : Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity 3 Publications
Chain Non-structural protein 5A : Host endoplasmic reticulum membrane; 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.3 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.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 168167Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei169 – 18921Helical; Reviewed prediction
Add
BLAST
Topological domaini190 – 358169Lumenal Reviewed prediction
Add
BLAST
Transmembranei359 – 37921Helical; Reviewed prediction
Add
BLAST
Topological domaini380 – 725346Lumenal Reviewed prediction
Add
BLAST
Transmembranei726 – 74621Helical; Reviewed prediction
Add
BLAST
Topological domaini747 – 75711Lumenal Reviewed prediction
Add
BLAST
Transmembranei758 – 77821Helical; Reviewed prediction
Add
BLAST
Topological domaini779 – 7824Cytoplasmic Reviewed prediction
Transmembranei783 – 80321Helical; Reviewed prediction
Add
BLAST
Topological domaini804 – 81310Lumenal Reviewed prediction
Transmembranei814 – 83421Helical; Reviewed prediction
Add
BLAST
Topological domaini835 – 88147Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei882 – 90221Helical; Reviewed prediction
Add
BLAST
Topological domaini903 – 92826Lumenal Reviewed prediction
Add
BLAST
Transmembranei929 – 94921Helical; Reviewed prediction
Add
BLAST
Topological domaini950 – 1657708Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei1658 – 167821Helical; Reviewed prediction
Add
BLAST
Topological domaini1679 – 1805127Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei1806 – 182621Helical; Reviewed prediction
Add
BLAST
Topological domaini1827 – 18282Lumenal Reviewed prediction
Transmembranei1829 – 184921Helical; Reviewed prediction
Add
BLAST
Topological domaini1850 – 18501Cytoplasmic Reviewed prediction
Transmembranei1851 – 187121Helical; Reviewed prediction
Add
BLAST
Topological domaini1872 – 188110Lumenal Reviewed prediction
Transmembranei1882 – 190221Helical; Reviewed prediction
Add
BLAST
Topological domaini1903 – 197270Cytoplasmic Reviewed prediction
Add
BLAST
Intramembranei1973 – 200230 Reviewed prediction
Add
BLAST
Topological domaini2003 – 2990988Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei2991 – 301121Helical; By similarity
Add
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
Mutagenesisi2001 – 20044PQLP → AQLA: No effect on binding to Src-family kinases.
Mutagenesisi2315 – 23184PLPP → ALAA: No effect on binding to Src-family kinases. 1 Publication
Mutagenesisi2322 – 23265PPVPP → APVAA: Complete loss of binding to GRB2 and Src-family kinases. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed; by host1 Publication
Chaini2 – 191190Core protein p21 Reviewed prediction
PRO_0000037517Add
BLAST
Chaini2 – 177176Core protein p19 By similarity
PRO_0000037518Add
BLAST
Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarity
PRO_0000037519Add
BLAST
Chaini192 – 383192Envelope glycoprotein E1 Reviewed prediction
PRO_0000037520Add
BLAST
Chaini384 – 746363Envelope glycoprotein E2 Reviewed prediction
PRO_0000037521Add
BLAST
Chaini747 – 80963p7 By similarity
PRO_0000037522Add
BLAST
Chaini810 – 1026217Protease NS2-3 Reviewed prediction
PRO_0000037523Add
BLAST
Chaini1027 – 1657631Serine protease NS3 Reviewed prediction
PRO_0000037524Add
BLAST
Chaini1658 – 171154Non-structural protein 4A Reviewed prediction
PRO_0000037525Add
BLAST
Chaini1712 – 1972261Non-structural protein 4B Reviewed prediction
PRO_0000037526Add
BLAST
Chaini1973 – 2420448Non-structural protein 5A Reviewed prediction
PRO_0000037527Add
BLAST
Chaini2421 – 3011591RNA-directed RNA polymerase Reviewed prediction
PRO_0000037528Add
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
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
Glycosylationi476 – 4761N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi532 – 5321N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi540 – 5401N-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 By similarity
Modified residuei2197 – 21971Phosphoserine; by host; in p58 By similarity
Modified residuei2201 – 22011Phosphoserine; by host; in p58 By similarity
Modified residuei2204 – 22041Phosphoserine; by host; in p58 By similarity
Modified residuei2321 – 23211Phosphoserine; by host By similarity

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases. The core protein is synthesized as a 21 kDa precursor which is retained in the ER membrane through the hydrophobic signal peptide. Cleavage by the signal peptidase releases the 19 kDa mature core protein. The other proteins (p7, NS2-3, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases By similarity.
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.
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

Miscellaneous databases

PMAP-CutDBP26664.

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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Acy3Q91XE46EBI-6941357,EBI-7378963From a different organism.
DDX3XO005713EBI-9209740,EBI-353779From a different organism.
STAT1P422245EBI-6941357,EBI-1057697From a different organism.

Protein-protein interaction databases

IntActiP26664. 4 interactions.
MINTiMINT-97561.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1032 – 10354
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 strandi1129 – 11335
Beta strandi1139 – 11446
Beta strandi1146 – 115712
Helixi1158 – 11603
Turni1161 – 11633
Beta strandi1168 – 11703
Turni1172 – 11743
Beta strandi1176 – 118611
Beta strandi1189 – 11979
Helixi1198 – 12058
Beta strandi1680 – 168910
Beta strandi2422 – 24265
Helixi2445 – 24506
Helixi2454 – 24563
Beta strandi2457 – 24593
Helixi2462 – 24643
Helixi2465 – 24728
Helixi2482 – 249514
Helixi2505 – 25106
Helixi2525 – 25295
Helixi2533 – 254816
Beta strandi2550 – 25523
Beta strandi2556 – 25605
Beta strandi2564 – 25663
Beta strandi2579 – 25824
Helixi2585 – 260723
Helixi2608 – 26103
Helixi2612 – 26143
Helixi2617 – 263014
Beta strandi2631 – 26399
Helixi2644 – 26474
Helixi2650 – 266011
Helixi2667 – 267913
Turni2680 – 26823
Beta strandi2684 – 26874
Beta strandi2693 – 26975
Helixi2707 – 272519
Beta strandi2729 – 27368
Beta strandi2739 – 27457
Helixi2749 – 276517
Beta strandi2770 – 27723
Beta strandi2777 – 27793
Helixi2780 – 27823
Beta strandi2788 – 27947
Beta strandi2800 – 28067
Helixi2809 – 282012
Helixi2827 – 28359
Helixi2839 – 28435
Helixi2845 – 285511
Beta strandi2863 – 28675
Beta strandi2870 – 28745
Helixi2876 – 28783
Helixi2879 – 28879
Helixi2889 – 28924
Helixi2899 – 291214
Helixi2917 – 293317
Helixi2936 – 294510
Helixi2947 – 29493
Helixi2960 – 29645
Turni2968 – 29714
Beta strandi2972 – 29754

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RTLX-ray2.75A/B1027-1207[»]
2A4GX-ray2.50A/C1027-1207[»]
2GVFX-ray2.50A/C1027-1207[»]
B/D1680-1696[»]
3EYDX-ray2.30A/C1027-1207[»]
B/D1680-1696[»]
3HKWX-ray1.55A/B/C2421-2990[»]
3KN2X-ray2.30A/C1027-1207[»]
3QGHX-ray2.14A2421-2990[»]
3QGIX-ray1.80A2421-2990[»]
3RC4X-ray1.50A1030-1208[»]
3RC5X-ray1.60A1030-1208[»]
ProteinModelPortaliP26664.
SMRiP26664. Positions 16-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.

Miscellaneous databases

EvolutionaryTraceiP26664.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini899 – 1026128Peptidase C18
Add
BLAST
Domaini1217 – 1369153Helicase ATP-binding
Add
BLAST
Domaini2634 – 2752119RdRp catalytic
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 5958Interaction with DDX3X By similarity
Add
BLAST
Regioni2 – 2322Interaction with STAT1 By similarity
Add
BLAST
Regioni122 – 17352Interaction with APOA2 By similarity
Add
BLAST
Regioni150 – 15910Mitochondrial targeting signal Inferred
Regioni164 – 1674Important for lipid droplets localization By similarity
Regioni265 – 29632Fusion peptide Reviewed prediction
Add
BLAST
Regioni385 – 41127HVR1 By similarity
Add
BLAST
Regioni475 – 4817HVR2 By similarity
Regioni482 – 49413CD81-binding 1 Reviewed prediction
Add
BLAST
Regioni522 – 55332CD81-binding 2 Reviewed prediction
Add
BLAST
Regioni660 – 67112PKR/eIF2-alpha phosphorylation homology domain (PePHD)
Add
BLAST
Regioni1679 – 169012NS3-binding (by NS4A) Reviewed prediction
Add
BLAST
Regioni2120 – 2332213Transcriptional activation Reviewed prediction
Add
BLAST
Regioni2120 – 220889FKBP8-binding Reviewed prediction
Add
BLAST
Regioni2200 – 225051Basal phosphorylation By similarity
Add
BLAST
Regioni2210 – 227566PKR-binding Reviewed prediction
Add
BLAST
Regioni2249 – 230658NS4B-binding Reviewed prediction
Add
BLAST
Regioni2351 – 242070Basal phosphorylation By similarity
Add
BLAST
Regioni2354 – 237724V3 By similarity
Add
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 biasi2286 – 232742Pro-rich
Add
BLAST
Compositional biasi2996 – 29994Poly-Leu

Domaini

The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2). E2 also contain two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2 and CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy By similarity.
The N-terminus of NS5A acts as membrane anchor. The central part of NS5A seems to be intrinsically disordered and interacts with NS5B and host PKR. The C-terminus of NS5A contains a variable region called variable region 3 (V3) By similarity.
The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases.
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.

Sequence similaritiesi

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR002518. HCV_NS2.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR013192. NS5A_1a.
IPR027417. P-loop_NTPase.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF07652. Flavi_DEAD. 1 hit.
PF01543. HCV_capsid. 1 hit.
PF01542. HCV_core. 1 hit.
PF01539. HCV_env. 1 hit.
PF01560. HCV_NS1. 1 hit.
PF01538. HCV_NS2. 1 hit.
PF01006. HCV_NS4a. 1 hit.
PF01001. HCV_NS4b. 1 hit.
PF01506. HCV_NS5a. 1 hit.
PF08300. HCV_NS5a_1a. 1 hit.
PF08301. HCV_NS5a_1b. 1 hit.
PF12941. HCV_NS5a_C. 1 hit.
PF02907. Peptidase_S29. 1 hit.
PF00998. RdRP_3. 1 hit.
[Graphical view]
ProDomiPD001388. HCV_env. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00487. DEXDc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS51693. HCV_NS2_PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by ribosomal frameshifting. Align

Note: The exact location of the ribosomal frameshift is unknown. The F protein seems to be generated by a -2 ribosomal frameshift located in the vicinity of codon 11 of the core protein coding sequence. However, some F proteins may also be generated by +1 ribosomal frameshift. Since the core gene encodes alternative reading frame proteins (ARFPs), many functions depicted for the core protein might belong to the ARFPs.

Isoform Genome polyprotein (identifier: P26664-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MSTNPKPQKK NKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR     50
KTSERSQPRG RRQPIPKARR PEGRTWAQPG YPWPLYGNEG CGWAGWLLSP 100
RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 150
LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTVPAS AYQVRNSTGL 200
YHVTNDCPNS SIVYEAADAI LHTPGCVPCV REGNASRCWV AMTPTVATRD 250
GKLPATQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRRHWT 300
TQGCNCSIYP GHITGHRMAW DMMMNWSPTT ALVMAQLLRI PQAILDMIAG 350
AHWGVLAGIA YFSMVGNWAK VLVVLLLFAG VDAETHVTGG SAGHTVSGFV 400
SLLAPGAKQN VQLINTNGSW HLNSTALNCN DSLNTGWLAG LFYHHKFNSS 450
GCPERLASCR PLTDFDQGWG PISYANGSGP DQRPYCWHYP PKPCGIVPAK 500
SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ENDTDVFVLN NTRPPLGNWF 550
GCTWMNSTGF TKVCGAPPCV IGGAGNNTLH CPTDCFRKHP DATYSRCGSG 600
PWITPRCLVD YPYRLWHYPC TINYTIFKIR MYVGGVEHRL EAACNWTRGE 650
RCDLEDRDRS ELSPLLLTTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ 700
YLYGVGSSIA SWAIKWEYVV LLFLLLADAR VCSCLWMMLL ISQAEAALEN 750
LVILNAASLA GTHGLVSFLV FFCFAWYLKG KWVPGAVYTF YGMWPLLLLL 800
LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS WCLWWLQYFL 850
TRVEAQLHVW IPPLNVRGGR DAVILLMCAV HPTLVFDITK LLLAVFGPLW 900
ILQASLLKVP YFVRVQGLLR FCALARKMIG GHYVQMVIIK LGALTGTYVY 950
NHLTPLRDWA HNGLRDLAVA VEPVVFSQME TKLITWGADT AACGDIINGL 1000
PVSARRGREI LLGPADGMVS KGWRLLAPIT AYAQQTRGLL GCIITSLTGR 1050
DKNQVEGEVQ IVSTAAQTFL ATCINGVCWT VYHGAGTRTI ASPKGPVIQM 1100
YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI PVRRRGDSRG 1150
SLLSPRPISY LKGSSGGPLL CPAGHAVGIF RAAVCTRGVA KAVDFIPVEN 1200
LETTMRSPVF TDNSSPPVVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK 1250
VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGSP ITYSTYGKFL 1300
ADGGCSGGAY DIIICDECHS TDATSILGIG TVLDQAETAG ARLVVLATAT 1350
PPGSVTVPHP NIEEVALSTT GEIPFYGKAI PLEVIKGGRH LIFCHSKKKC 1400
DELAAKLVAL GINAVAYYRG LDVSVIPTSG DVVVVATDAL MTGYTGDFDS 1450
VIDCNTCVTQ TVDFSLDPTF TIETITLPQD AVSRTQRRGR TGRGKPGIYR 1500
FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV 1550
CQDHLEFWEG VFTGLTHIDA HFLSQTKQSG ENLPYLVAYQ ATVCARAQAP 1600
PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEITLTHP VTKYIMTCMS 1650
ADLEVVTSTW VLVGGVLAAL AAYCLSTGCV VIVGRVVLSG KPAIIPDREV 1700
LYREFDEMEE CSQHLPYIEQ GMMLAEQFKQ KALGLLQTAS RQAEVIAPAV 1750
QTNWQKLETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTAAVTSP 1800
LTTSQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAAIG SVGLGKVLID 1850
ILAGYGAGVA GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALVVGVVCAA 1900
ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTAILSS 1950
LTVTQLLRRL HQWISSECTT PCSGSWLRDI WDWICEVLSD FKTWLKAKLM 2000
PQLPGIPFVS CQRGYKGVWR VDGIMHTRCH CGAEITGHVK NGTMRIVGPR 2050
TCRNMWSGTF PINAYTTGPC TPLPAPNYTF ALWRVSAEEY VEIRQVGDFH 2100
YVTGMTTDNL KCPCQVPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG 2150
LHEYPVGSQL PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSVAS 2200
SSASQLSAPS LKATCTANHD SPDAELIEAN LLWRQEMGGN ITRVESENKV 2250
VILDSFDPLV AEEDEREISV PAEILRKSRR FAQALPVWAR PDYNPPLVET 2300
WKKPDYEPPV VHGCPLPPPK SPPVPPPRKK RTVVLTESTL STALAELATR 2350
SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DAESYSSMPP LEGEPGDPDL 2400
SDGSWSTVSS EANAEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL 2450
LRHHNLVYST TSRSACQRQK KVTFDRLQVL DSHYQDVLKE VKAAASKVKA 2500
NLLSVEEACS LTPPHSAKSK FGYGAKDVRC HARKAVTHIN SVWKDLLEDN 2550
VTPIDTTIMA KNEVFCVQPE KGGRKPARLI VFPDLGVRVC EKMALYDVVT 2600
KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGFSYD TRCFDSTVTE 2650
SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR 2700
ASGVLTTSCG NTLTCYIKAR AACRAAGLQD CTMLVCGDDL VVICESAGVQ 2750
EDAASLRAFT EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR 2800
VYYLTRDPTT PLARAAWETA RHTPVNSWLG NIIMFAPTLW ARMILMTHFF 2850
SVLIARDQLE QALDCEIYGA CYSIEPLDLP PIIQRLHGLS AFSLHSYSPG 2900
EINRVAACLR KLGVPPLRAW RHRARSVRAR LLARGGRAAI CGKYLFNWAV 2950
RTKLKLTPIA AAGQLDLSGW FTAGYSGGDI YHSVSHARPR WIWFCLLLLA 3000
AGVGIYLLPN R 3011

Note: Produced by conventional translation.

Length:3,011
Mass (Da):327,202
Last modified:January 23, 2007 - v3
Checksum:i65F8C9447FCE5AF9
GO
Isoform F protein (identifier: P0C044-1) [UniParc]FASTAAdd to Basket

Also known as: Frameshifted protein

The sequence of this isoform can be found in the external entry P0C044.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by ribosomal frameshifting.

Length:162
Mass (Da):17,002
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 113KKN → RKT in infectious clone pHCV-1/SF.
Natural varianti399 – 3991F → S in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti402 – 4021L → F in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti929 – 9291I → A in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti1703 – 17031R → Q in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti2021 – 20211V → G in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti2349 – 23502TR → IK in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti2378 – 23781P → R in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti2413 – 24131N → S in strain: Isolate infectious clone pHCV-1/SF.
Natural varianti2992 – 29921I → F in strain: Isolate infectious clone pHCV-1/SF.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M62321 Genomic RNA. Translation: AAA45676.1.
AF271632 Genomic RNA. Translation: AAF81759.1.
PIRiA39166. GNWVC3.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Cross-referencesi

Web resourcesi

euHCVdb

The European HCV database

Virus Pathogen Resource

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M62321 Genomic RNA. Translation: AAA45676.1 .
AF271632 Genomic RNA. Translation: AAF81759.1 .
PIRi A39166. GNWVC3.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1RTL X-ray 2.75 A/B 1027-1207 [» ]
2A4G X-ray 2.50 A/C 1027-1207 [» ]
2GVF X-ray 2.50 A/C 1027-1207 [» ]
B/D 1680-1696 [» ]
3EYD X-ray 2.30 A/C 1027-1207 [» ]
B/D 1680-1696 [» ]
3HKW X-ray 1.55 A/B/C 2421-2990 [» ]
3KN2 X-ray 2.30 A/C 1027-1207 [» ]
3QGH X-ray 2.14 A 2421-2990 [» ]
3QGI X-ray 1.80 A 2421-2990 [» ]
3RC4 X-ray 1.50 A 1030-1208 [» ]
3RC5 X-ray 1.60 A 1030-1208 [» ]
ProteinModelPortali P26664.
SMRi P26664. Positions 16-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
ModBasei Search...

Protein-protein interaction databases

IntActi P26664. 4 interactions.
MINTi MINT-97561.

Chemistry

ChEMBLi CHEMBL4620.

Protein family/group databases

MEROPSi C18.001.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

euHCVdbi AF271632.
M62321.

Enzyme and pathway databases

SABIO-RK P26664.

Miscellaneous databases

EvolutionaryTracei P26664.
PMAP-CutDB P26664.

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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Infectious cDNA clone of the hepatitis C virus genotype 1 prototype sequence."
    Lanford R.E., Lee H., Chavez D., Guerra B., Brasky K.M.
    J. Gen. Virol. 82:1291-1297(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Infectious clone pHCV-1/SF.
  3. "Differential subcellular localization of hepatitis C virus core gene products."
    Lo S.-Y., Masiarz F., Hwang S.B., Lai M.M.C., Ou J.-H.
    Virology 213:455-461(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION OF CORE PROTEIN.
  4. "Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein."
    Ray R.B., Lagging L.M., Meyer K., Steele R., Ray R.
    Virus Res. 37:209-220(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  5. "Interaction between hepatitis C virus core protein and E1 envelope protein."
    Lo S.-Y., Selby M.J., Ou J.-H.
    J. Virol. 70:5177-5182(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF CORE PROTEIN WITH E1 PROTEIN.
  6. "Suppression of apoptotic cell death by hepatitis C virus core protein."
    Ray R.B., Meyer K., Ray R.
    Virology 226:176-182(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  7. "Transcriptional repression of p53 promoter by hepatitis C virus core protein."
    Ray R.B., Steele R., Meyer K., Ray R.
    J. Biol. Chem. 272:10983-10986(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  8. "Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein."
    Gale M.J. Jr., Korth M.J., Tang N.M., Tan S.-L., Hopkins D.A., Dever T.E., Polyak S.J., Gretch D.R., Katze M.G.
    Virology 230:217-227(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF NS5A WITH HUMAN EIF2AK2/PKR.
  9. "Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity."
    Ray R.B., Steele R., Meyer K., Ray R.
    Gene 208:331-336(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  10. "Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors."
    Shrivastava A., Manna S.K., Ray R., Aggarwal B.B.
    J. Virol. 72:9722-9728(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF CORE PROTEIN.
  11. "Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein."
    Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M.C.
    Science 285:107-110(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF E2 WITH HUMAN EIF2AK2/PKR.
  12. "Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain."
    Taylor D.R., Tian B., Romano P.R., Hinnebusch A.G., Lai M.M.C., Mathews M.B.
    J. Virol. 75:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF E2.
  13. "Membrane topology of the hepatitis C virus NS2 protein."
    Yamaga A.K., Ou J.-H.
    J. Biol. Chem. 277:33228-33234(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY OF NS2 PROTEIN.
  14. "The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity."
    Macdonald A., Crowder K., Street A., McCormick C., Harris M.
    J. Gen. Virol. 85:721-729(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF NS5A WITH HUMAN SRC-FAMILY KINASES, MUTAGENESIS OF 2001-PRO--PRO-2004; 2315-PRO--PRO-2318 AND 2322-PRO--PRO-2326.
  15. "Targeting of hepatitis C virus core protein to mitochondria through a novel C-terminal localization motif."
    Schwer B., Ren S., Pietschmann T., Kartenbeck J., Kaehlcke K., Bartenschlager R., Yen T.S.B., Ott M.
    J. Virol. 78:7958-7968(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN.
  16. "Hepatitis C virus (HCV) NS5A protein downregulates HCV IRES-dependent translation."
    Kalliampakou K.I., Kalamvoki M., Mavromara P.
    J. Gen. Virol. 86:1015-1025(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF NS5A.
  17. "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.
  18. Cited for: REVIEW, SUBCELLULAR LOCATION.
  19. "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication."
    Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.
    J. Virol. 81:3852-3865(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HNRNPA1 AND SEPT6.

Entry informationi

Entry nameiPOLG_HCV1
AccessioniPrimary (citable) accession number: P26664
Secondary accession number(s): Q9IFE5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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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