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O92972

- POLG_HCVJ4

UniProt

O92972 - POLG_HCVJ4

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Protein
Genome polyprotein
Gene
N/A
Organism
Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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

Catalytic activityi

Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
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
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. 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: IntAct
  8. protein kinase binding Source: AgBase
  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 (strain HC-J4) (HCV)
Taxonomic identifieri420174 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000008094: Genome

Subcellular locationi

Chain Core protein p21 : Host endoplasmic reticulum membrane; 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.
Chain Core protein p19 : Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity
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.
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.
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.
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.
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.
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.
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.

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 By similarity
Add
BLAST
Topological domaini2003 – 2989987Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei2990 – 301021Helical; By similarity
Add
BLAST

GO - Cellular componenti

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

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 prediction
PRO_0000278742Add
BLAST
Chaini2 – 177176Core protein p19 By similarity
PRO_0000278743Add
BLAST
Propeptidei178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarity
PRO_0000278744Add
BLAST
Chaini192 – 383192Envelope glycoprotein E1 Reviewed prediction
PRO_0000278745Add
BLAST
Chaini384 – 746363Envelope glycoprotein E2 Reviewed prediction
PRO_0000278746Add
BLAST
Chaini747 – 80963p7 By similarity
PRO_0000278747Add
BLAST
Chaini810 – 1026217Protease NS2-3 Reviewed prediction
PRO_0000278748Add
BLAST
Chaini1027 – 1657631Serine protease NS3 Reviewed prediction
PRO_0000278749Add
BLAST
Chaini1658 – 171154Non-structural protein 4A Reviewed prediction
PRO_0000278750Add
BLAST
Chaini1712 – 1972261Non-structural protein 4B Reviewed prediction
PRO_0000278751Add
BLAST
Chaini1973 – 2419447Non-structural protein 5A Reviewed prediction
PRO_0000278752Add
BLAST
Chaini2420 – 3010591RNA-directed RNA polymerase Reviewed prediction
PRO_0000278753Add
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
Glycosylationi478 – 4781N-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
Modified residuei2194 – 21941Phosphoserine; by host; in p56 Inferred
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

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.
Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation By similarity.
NS5A is phosphorylated in a basal form termed p56. p58 is a hyperphosphorylated form of p56. p56 and p58 coexist in the cell in roughly equivalent amounts. Hyperphosphorylation is dependent on the presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6 and CSNK1A1/CKI-alpha kinases may be responsible for NS5A phosphorylation By similarity.
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.

Keywords - PTMi

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

Interactioni

Subunit structurei

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

Binary interactionsi

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

Protein-protein interaction databases

IntActiO92972. 10 interactions.

Structurei

Secondary structure

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

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiO92972.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini903 – 1026124Peptidase C18
Add
BLAST
Domaini1217 – 1369153Helicase ATP-binding
Add
BLAST
Domaini2633 – 2751119RdRp 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 By similarity
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) By similarity
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
Regioni2210 – 224940ISDR By similarity
Add
BLAST
Regioni2249 – 230658NS4B-binding Reviewed prediction
Add
BLAST
Regioni2351 – 241969Basal 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 biasi2282 – 232746Pro-rich
Add
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.
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 By similarity.
The N-terminal one-third of serine protease NS3 contains the protease activity. This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role. This region is essential for the activity of protease NS2-3, maybe by contributing to the folding of the latter. The helicase activity is located in the C-terminus of NS3 By similarity.

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]

Sequencei

Sequence statusi: Complete.

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

O92972-1 [UniParc]FASTAAdd to Basket

« Hide

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

Natural variant

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

Sequence databases

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

Cross-referencesi

Web resourcesi

euHCVdb

The European HCV database

Virus Pathogen Resource

Sequence databases

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

3D structure databases

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

Protein-protein interaction databases

IntActi O92972. 10 interactions.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

euHCVdbi AF054247.
AF054248.
AF054249.
AF054250.
D10750.

Miscellaneous databases

EvolutionaryTracei O92972.

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR002518. HCV_NS2.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR013192. NS5A_1a.
IPR027417. P-loop_NTPase.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF07652. Flavi_DEAD. 1 hit.
PF01543. HCV_capsid. 1 hit.
PF01542. HCV_core. 1 hit.
PF01539. HCV_env. 1 hit.
PF01560. HCV_NS1. 1 hit.
PF01538. HCV_NS2. 1 hit.
PF01006. HCV_NS4a. 1 hit.
PF01001. HCV_NS4b. 1 hit.
PF01506. HCV_NS5a. 1 hit.
PF08300. HCV_NS5a_1a. 1 hit.
PF08301. HCV_NS5a_1b. 1 hit.
PF12941. HCV_NS5a_C. 1 hit.
PF02907. Peptidase_S29. 1 hit.
PF00998. RdRP_3. 1 hit.
[Graphical view ]
ProDomi PD001388. HCV_env. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SMARTi SM00487. DEXDc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEi PS51693. HCV_NS2_PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability."
    Okamoto H., Kojima M., Okada S., Yoshizawa H., Iizuka H., Tanaka T., Muchmore E.E., Peterson D.A., Ito Y., Mishiro S.
    Virology 190:894-899(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Isolate HC-J4/91.
  2. "Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo."
    Yanagi M., St Claire M., Shapiro M., Emerson S.U., Purcell R.H., Bukh J.
    Virology 244:161-172(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: HC-J4, Isolate pCV-J4L2S, Isolate pCV-J4L4S and Isolate pCV-J4L6S.
  3. "Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro."
    Clarke D., Griffin S., Beales L., Gelais C.S., Burgess S., Harris M., Rowlands D.
    J. Biol. Chem. 281:37057-37068(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  4. "Biochemical and pre-steady-state kinetic characterization of the hepatitis C virus RNA polymerase (NS5BDelta21, HC-J4)."
    Cramer J., Jaeger J., Restle T.
    Biochemistry 45:3610-3619(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF NS5B, SUBUNIT.
    Strain: Isolate pCV-J4L6S.
  5. "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication."
    Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.
    J. Virol. 81:3852-3865(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HNRNPA1 AND SEPT6.
  6. "Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation."
    O'Farrell D., Trowbridge R., Rowlands D., Jager J.
    J. Mol. Biol. 326:1025-1035(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2420-2989.

Entry informationi

Entry nameiPOLG_HCVJ4
AccessioniPrimary (citable) accession number: O92972
Secondary accession number(s): O92969
, O92970, O92971, Q02828
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Caution

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

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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