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Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 3a (isolate k3a) (HCV)
Status
Reviewed-Annotation score: 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).By similarity
E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).By similarity
P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).By similarity
Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).By similarity
NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/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).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).By similarity
NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).By similarity
NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication.By similarity

Catalytic activityi

Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per NS3 protease domain.By similarity
  • Zn2+By similarityNote: 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei164Responsible for increased FAS up-regulationBy similarity1
Active sitei958For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei978For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei999For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei1089Charge relay system; for serine protease NS3 activityBy similarity1
Active sitei1113Charge relay system; for serine protease NS3 activityBy similarity1
Metal bindingi1129ZincBy similarity1
Metal bindingi1131ZincBy similarity1
Active sitei1171Charge relay system; for serine protease NS3 activityBy similarity1
Metal bindingi1177ZincBy similarity1
Metal bindingi1181ZincBy similarity1
Metal bindingi2017ZincBy similarity1
Metal bindingi2035ZincBy similarity1
Metal bindingi2037ZincBy similarity1
Metal bindingi2058ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1236 – 1243ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

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 3a (isolate k3a) (HCV)
Taxonomic identifieri356416 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008099 Componenti: Genome

Subcellular locationi

Core protein p21 :
Core protein p19 :
Envelope glycoprotein E1 :
  • Virion membrane Curated; Single-pass type I membrane protein Curated
  • Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E1 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
Envelope glycoprotein E2 :
  • Virion membrane Curated; Single-pass type I membrane protein Curated
  • Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E2 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
p7 :
Serine protease NS3 :
Non-structural protein 4A :
Non-structural protein 5A :
RNA-directed RNA polymerase :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 168CytoplasmicSequence analysisAdd BLAST167
Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 358LumenalSequence analysisAdd BLAST169
Transmembranei359 – 379HelicalSequence analysisAdd BLAST21
Topological domaini380 – 731LumenalSequence analysisAdd BLAST352
Transmembranei732 – 752HelicalSequence analysisAdd BLAST21
Topological domaini753 – 763LumenalSequence analysisAdd BLAST11
Transmembranei764 – 784HelicalSequence analysisAdd BLAST21
Topological domaini785 – 788CytoplasmicSequence analysis4
Transmembranei789 – 809HelicalSequence analysisAdd BLAST21
Topological domaini810 – 819LumenalSequence analysis10
Transmembranei820 – 840HelicalSequence analysisAdd BLAST21
Topological domaini841 – 887CytoplasmicSequence analysisAdd BLAST47
Transmembranei888 – 908HelicalSequence analysisAdd BLAST21
Topological domaini909 – 934LumenalSequence analysisAdd BLAST26
Transmembranei935 – 955HelicalSequence analysisAdd BLAST21
Topological domaini956 – 1663CytoplasmicSequence analysisAdd BLAST708
Transmembranei1664 – 1684HelicalSequence analysisAdd BLAST21
Topological domaini1685 – 1811CytoplasmicSequence analysisAdd BLAST127
Transmembranei1812 – 1832HelicalSequence analysisAdd BLAST21
Topological domaini1833 – 1834LumenalSequence analysis2
Transmembranei1835 – 1855HelicalSequence analysisAdd BLAST21
Topological domaini1856CytoplasmicSequence analysis1
Transmembranei1857 – 1877HelicalSequence analysisAdd BLAST21
Topological domaini1878 – 1887LumenalSequence analysis10
Transmembranei1888 – 1908HelicalSequence analysisAdd BLAST21
Topological domaini1909 – 1978CytoplasmicSequence analysisAdd BLAST70
Intramembranei1979 – 2008By similarityAdd BLAST30
Topological domaini2009 – 3000CytoplasmicSequence analysisAdd BLAST992
Transmembranei3001 – 3021HelicalBy similarityAdd BLAST21

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostBy similarity
ChainiPRO_00000456402 – 191Core protein p21Sequence analysisAdd BLAST190
ChainiPRO_00000456412 – 177Core protein p19By similarityAdd BLAST176
PropeptideiPRO_0000045642178 – 191ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityAdd BLAST14
ChainiPRO_0000045643192 – 383Envelope glycoprotein E1Sequence analysisAdd BLAST192
ChainiPRO_0000045644384 – 752Envelope glycoprotein E2Sequence analysisAdd BLAST369
ChainiPRO_0000045645753 – 815p7By similarityAdd BLAST63
ChainiPRO_0000045646816 – 1032Protease NS2-3PROSITE-ProRule annotationAdd BLAST217
ChainiPRO_00000456471033 – 1663Serine protease NS3Sequence analysisAdd BLAST631
ChainiPRO_00000456481664 – 1717Non-structural protein 4ASequence analysisAdd BLAST54
ChainiPRO_00000456491718 – 1978Non-structural protein 4BSequence analysisAdd BLAST261
ChainiPRO_00000456501979 – 2430Non-structural protein 5ASequence analysisAdd BLAST452
ChainiPRO_00000456512431 – 3021RNA-directed RNA polymeraseSequence analysisAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine; by hostBy similarity1
Modified residuei53Phosphoserine; by hostBy similarity1
Modified residuei99Phosphoserine; by hostBy similarity1
Modified residuei116Phosphoserine; by host PKABy similarity1
Glycosylationi196N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi209N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi234N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi305N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi417N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi423N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi430N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi448N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi476N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi533N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi557N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi581N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi629N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi651N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi1978S-palmitoyl cysteine; by hostBy similarity1
Disulfide bondi2120 ↔ 2168By similarity
Modified residuei2200Phosphoserine; by host; in p56By similarity1
Modified residuei2203Phosphoserine; by host; in p58By similarity1
Modified residuei2207Phosphoserine; by host; in p58By similarity1
Modified residuei2210Phosphoserine; by host; in p58By similarity1

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases. The core protein is synthesized as a 21 kDa precursor which is retained in the ER membrane through the hydrophobic signal peptide. Cleavage by the signal peptidase releases the 19 kDa mature core protein. The other proteins (p7, NS2-3, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity).By similarity
Envelope E1 and E2 glycoproteins are highly N-glycosylated.By similarity
Core protein is phosphorylated by host PKC and PKA.By similarity
NS5A is phosphorylated in a basal form termed p56. p58 is a hyperphosphorylated form of p56. p56 and p58 coexist in the cell in roughly equivalent amounts. Hyperphosphorylation is dependent on the presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6 and CSNK1A1/CKI-alpha kinases may be responsible for NS5A phosphorylation (By similarity).By similarity
NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions (By similarity).By similarity
The N-terminus of a fraction of NS4B molecules seems to be relocated post-translationally from the cytoplasm to the ER lumen, with a 5th transmembrane segment. The C-terminus of NS2 may be lumenal with a fourth transmembrane segment (By similarity).By similarity
Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei177 – 178Cleavage; by host signal peptidaseBy similarity2
Sitei?191 – ?192Cleavage; by host signal peptidaseSequence analysis2
Sitei383 – 384Cleavage; by host signal peptidaseSequence analysis2
Sitei752 – 753Cleavage; by host signal peptidaseBy similarity2
Sitei815 – 816Cleavage; by host signal peptidaseBy similarity2
Sitei1032 – 1033Cleavage; by protease NS2-3PROSITE-ProRule annotation2
Sitei1663 – 1664Cleavage; by serine protease NS3Sequence analysis2
Sitei1717 – 1718Cleavage; by serine protease NS3Sequence analysis2
Sitei1978 – 1979Cleavage; by serine protease NS3Sequence analysis2
Sitei2430 – 2431Cleavage; by serine protease NS3Sequence analysis2

Keywords - PTMi

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

Proteomic databases

PRIDEiQ81495.

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ81495.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini905 – 1032Peptidase C18PROSITE-ProRule annotationAdd BLAST128
Domaini1223 – 1375Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST153
Domaini1382 – 1544Helicase C-terminalPROSITE-ProRule annotationAdd BLAST163
Domaini2644 – 2762RdRp catalyticPROSITE-ProRule annotationAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 59Interaction with DDX3XBy similarityAdd BLAST58
Regioni2 – 23Interaction with STAT1By similarityAdd BLAST22
Regioni122 – 173Interaction with APOA2By similarityAdd BLAST52
Regioni150 – 159Mitochondrial targeting signalBy similarity10
Regioni164 – 167Important for lipid droplets localizationBy similarity4
Regioni265 – 296Fusion peptideSequence analysisAdd BLAST32
Regioni385 – 411HVR1By similarityAdd BLAST27
Regioni483 – 495CD81-binding 1Sequence analysisAdd BLAST13
Regioni523 – 554CD81-binding 2Sequence analysisAdd BLAST32
Regioni666 – 677PKR/eIF2-alpha phosphorylation homology domain (PePHD)By similarityAdd BLAST12
Regioni1685 – 1696NS3-binding (by NS4A)Sequence analysisAdd BLAST12
Regioni2126 – 2338Transcriptional activationSequence analysisAdd BLAST213
Regioni2126 – 2214FKBP8-bindingSequence analysisAdd BLAST89
Regioni2206 – 2256Basal phosphorylationBy similarityAdd BLAST51
Regioni2216 – 2281PKR-bindingSequence analysisAdd BLAST66
Regioni2255 – 2312NS4B-bindingSequence analysisAdd BLAST58
Regioni2357 – 2430Basal phosphorylationBy similarityAdd BLAST74

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi5 – 13Nuclear localization signalSequence analysis9
Motifi38 – 43Nuclear localization signalSequence analysis6
Motifi58 – 64Nuclear localization signalSequence analysis7
Motifi66 – 71Nuclear localization signalSequence analysis6
Motifi1322 – 1325DECH boxBy similarity4
Motifi2328 – 2331SH3-bindingSequence analysis4
Motifi2333 – 2341Nuclear localization signalSequence analysis9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2284 – 2333Pro-richAdd BLAST50
Compositional biasi2357 – 2476Ser-richAdd BLAST120
Compositional biasi3002 – 3009Poly-Leu8

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 a highly variable region called hypervariable region 1 (HVR1). E2 also contains two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy (By similarity).By similarity
The N-terminus of NS5A acts as membrane anchor. The central part of NS5A seems to be intrinsically disordered and interacts with NS5B and host PKR (By similarity).By similarity
The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases.By similarity
The N-terminal one-third of serine protease NS3 contains the protease activity. This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role. This region is essential for the activity of protease NS2-3, maybe by contributing to the folding of the latter. The helicase activity is located in the C-terminus of NS3 (By similarity).By similarity

Sequence similaritiesi

Belongs to the hepacivirus polyprotein family.Curated
Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation
Contains 1 peptidase C18 domain.PROSITE-ProRule annotation
Contains 1 peptidase S29 domain.Curated
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR002518. HCV_NS2.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR013192. NS5A_1a.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
[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.
PS51194. HELICASE_CTER. 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.

Q81495-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTLPKPQRK TKRNTIRRPQ DVKFPGGGVI YVGVYVLPRR GPRLGVRATR
60 70 80 90 100
KTSERSQPRG RRKPIPKARR SEGRSWAQPG YPWPLYGNEG CGWAGWLLSP
110 120 130 140 150
RGSRPNWAPN DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA
160 170 180 190 200
LAHGVRALED GINFATGNLP GCSFSIFLLA LFSCLIHPAA SLEWRNTSGL
210 220 230 240 250
YVLTNDCSNS SIVYEADDVI LHTPGCIPCV QDGNTSTCWT PVTPTVAVRY
260 270 280 290 300
VGATTASIRS HVDLLVGAGT MCSALYVGDM CGPVFLVGQA FTFRPRRHRT
310 320 330 340 350
VQTCNCSLYP GHLSGQRMAW DMMMNWSPAV GMVVAHILRL PQTLFDVVAG
360 370 380 390 400
AHWGIIAGLA YYSMQGNWAK VAIIMVMFSG VDASTHVTAG QAARNAYGIT
410 420 430 440 450
SLFSVGAKQN LQLINTNGSW HINRTALNCN ESINTGFIAG LFYYHKFNST
460 470 480 490 500
GCPQRLSSCK PITFFKQGWG PLTDANITGP SDDKPYCWHY APRPCGIVPA
510 520 530 540 550
LNVCGPVYCF TPSPVVVGTT DAKGAPTYTW GANKTDVFLL ESLRPPSGRW
560 570 580 590 600
FGCTWMNSTG FVKTCGAPPC NIYGDGRDAQ NESDLFCPTD CFRKHPEATY
610 620 630 640 650
SRCGAGPWLT PRCLVDYPYR LWHYPCTVNF TLFKVRMFVG GFEHRFTAAC
660 670 680 690 700
NWTRGERCDI EDRDRSEQHP LLHSTTELAI LPCSFTPMPA LSTGLIHLHQ
710 720 730 740 750
NIVDVQYLYG IGSGMVGWAL KWEFVILIFL LLADARVCVA LWLILTISQA
760 770 780 790 800
EAALENLVTL NAVAAAGTHG IGWYLVAFCA AWYVRGKLVP LVTYSLTGLW
810 820 830 840 850
SLALLVLLLP QRAYAWSGED SATLGAGILV LFGFFTLSPW YKHWIARLIW
860 870 880 890 900
WNQYTICRCE SALHVWVPPL LARGGRDGVI LLTSLLYPSL IFDITKLLIA
910 920 930 940 950
ALGPLYLIQA TITATPYFVR AHVLVRLCML VRSVMGGKYF QMIILSLADG
960 970 980 990 1000
SNTYLYDHLA PMQHWAAAGL KDLAVATEPV IFSPMEIKVI TWGADTAACG
1010 1020 1030 1040 1050
DILCGLPVSA RLGREVLLGP ADDYREMGWR LLAPITAYAQ QTRGLLGTIV
1060 1070 1080 1090 1100
TSLTGRDKNV VAGEVQVLST ATQTFLGTTV GGVMWTVYHG AGSRTLAGVK
1110 1120 1130 1140 1150
HPALQMYTNV DQDLVGWPAP PGAKSLEPCT CGSADLYLVT RDADVIPARR
1160 1170 1180 1190 1200
RGDSTASLLS PRPLARLKGS SGGPVMCPSG HVAGIFRAAV CTRGVAKALQ
1210 1220 1230 1240 1250
FIPVETLSTQ ARSPSFSDNS TPPAVPQSYQ VGYLHAPTGS GKSTKVPAAY
1260 1270 1280 1290 1300
VAQGYNVLVL NPSVAATLGF GSFMSRAYGI DPNIRTGNRT VTTGAKLTYS
1310 1320 1330 1340 1350
TYGKFLAGGG CSGGAYDVII CDDCHAQDAT SILGIGTVLD QAETAGVRLT
1360 1370 1380 1390 1400
VLATATPPGS ITVPHSNIEE VALGSEGEIP FYGKAIPIAC IKGGRHLIFC
1410 1420 1430 1440 1450
HSKKKCDKMA SKLRGMGLNA VAYYRGLDVS VIPTTGDVVV CATDALMTGF
1460 1470 1480 1490 1500
TGDFDSVIDC NVAVEQYVDF SLDPTFSIET CTAPQDAVSR SQRRGRTGRG
1510 1520 1530 1540 1550
RLGTYRYVTP GERPSGMFDS VVLCECYDAG CSWYDLQPAE TTVRLRAYLS
1560 1570 1580 1590 1600
TPGLPVCQDH LDLWESVFTG LTHIDAHFLS QTKQAGLNFS YLTAYQATVC
1610 1620 1630 1640 1650
ARAQAPPPSW DETWKCLVRL KPTLHGPTPL LYRLGPVQNE ICLTHPITKY
1660 1670 1680 1690 1700
VMACMSADLE VTTSTWVLLG GVLAAVAAYC LSVGCVVIVG HIELGGKPAL
1710 1720 1730 1740 1750
VPDKEVLYQQ YDEMEECSQA RPYIEQAQVI AHQFKEKVLG LLQRATQQQA
1760 1770 1780 1790 1800
VIEPIVVSNW QKLEVLWHKH MWNFVSGIQY LAGLSTLPGN PAVASLMAFT
1810 1820 1830 1840 1850
ASVTSPLTTN QTMFFNILGG WVATHLAGPQ ASSAFVVSGL AGAAIGGIGL
1860 1870 1880 1890 1900
GRVLLDILAG YGAGVSGALV AFKIMGGEPP TTEDMVNLLP AILSPGALVV
1910 1920 1930 1940 1950
GVICAAILRR HVGPGEGPVQ WMNRLIAFAS RGNHVSPAHY VPESDAAARV
1960 1970 1980 1990 2000
TALLSSLTVT SLLRRLHQWI NEDYPSPCSG DWLRIIWDWV CSVVSDFKTW
2010 2020 2030 2040 2050
LSAKIMPALP GLPFISCQKG YKGVWRGDGV MSTRCPCGAS IAGHVKNGSM
2060 2070 2080 2090 2100
RLAGPRTCAN MCHGTFPINE YTTGPSTPCP PPNYTRALWR VAANSYVEVR
2110 2120 2130 2140 2150
RVGDFHYITG ATEDGLKCPC QVPATEFFTE VDGVRIHRYA PPCRPLLRDE
2160 2170 2180 2190 2200
ITFMVGLNSY AIGSQLPCEP EPDVSVLTSM LRDPSHITAE TAARRLARGS
2210 2220 2230 2240 2250
PPSEASSSAS QLSAPSLKAT CQTHRPHPDA ELVDANLLWR QEMGSNITRV
2260 2270 2280 2290 2300
ESETKVVILD SFEPLRAETD DAELSAAAEC FKKPPKYPPA LPIWARPDYN
2310 2320 2330 2340 2350
PPLLDRWKSP DYVPPTVHGC ALPPKGAPPV PPPRRKRTIQ LDGSNVSAAL
2360 2370 2380 2390 2400
AALAEKSFPS SKPQEENSSS SGVDTQSSTA SKVLPSPGEE SDSESCSSMP
2410 2420 2430 2440 2450
PLEGEPGDPD LSCDSWSTVS DSEEQSVVCC SMSYSWTGAL ITPCSAEEEK
2460 2470 2480 2490 2500
LPISPLSNSL LRHHNLVYST SSRSASQRQK KVTFDRLQVL DDHYKTALQE
2510 2520 2530 2540 2550
VKERASRVKA RMLSIEEACA LVPPHSARSK FGYSAKDVRS LSSKAINQIR
2560 2570 2580 2590 2600
SVWEDLLEDT TTPIPTTIMA KNEVFCVDPA KGGRKAARLI VYPDLGVRVC
2610 2620 2630 2640 2650
EKRALYDVIQ RLSIETMGSA YGFQYSPRQR VERLLKMWTS KKTPLGFSYD
2660 2670 2680 2690 2700
TRCFDSTVTG QDIRVEEAVY QCCNLEPEPG QAISSLTERL YCGGPMNNSK
2710 2720 2730 2740 2750
GAQCGYLRCR ASGVLPTSFG NTITCYIKAT AAARAAGLRN PDFLVCGDDL
2760 2770 2780 2790 2800
VVVAESDGVD EDRATLRAFT EAMTRYSAPP GDAPQPTYDL ELITSCSSNV
2810 2820 2830 2840 2850
SVARDDKGKR YYYLTRDATT PLARAAWETA RHTPVNSWLG SIIMYAPTIW
2860 2870 2880 2890 2900
VRMVMMTHFF SILQSQEILD RPLDFEMYGA TYSVTPLDLP AIIERLHGLS
2910 2920 2930 2940 2950
AFSVHSYSPV ELNRVAGTLR KLGCPPLRAW RHRARAVRAK LIAQGGRAKI
2960 2970 2980 2990 3000
CGLYLFNWAV RTKTKLTPLP AAGQLDLSSW FTVGVGGNDI YHSVSRARTR
3010 3020
YLLLCLLLLT VGVGIFLLPA R
Length:3,021
Mass (Da):328,390
Last modified:January 23, 2007 - v3
Checksum:iA97418FF36C062A4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28917 Genomic RNA. Translation: BAA06044.1.

Cross-referencesi

Web resourcesi

euHCVdb

The European HCV database

Virus Pathogen Resource

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28917 Genomic RNA. Translation: BAA06044.1.

3D structure databases

ProteinModelPortaliQ81495.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ81495.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

euHCVdbiD28917.

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.
IPR009003. Peptidase_S1_PA.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
[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.
PS51194. HELICASE_CTER. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPOLG_HCVK3
AccessioniPrimary (citable) accession number: Q81495
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 136 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
Core protein of HCV genotype 3a induces increased amount of triglyceride accumulation over other genotypes.

Caution

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

Keywords - Technical termi

Complete proteome, Multifunctional enzyme

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.