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P26660 (POLG_HCVJ6) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Genome polyprotein

Cleaved into the following 11 chains:

  1. Core protein p21
    Alternative name(s):
    Capsid protein C
    p21
  2. Core protein p19
  3. Envelope glycoprotein E1
    Alternative name(s):
    gp32
    gp35
  4. Envelope glycoprotein E2
    Alternative name(s):
    NS1
    gp68
    gp70
  5. p7
  6. Protease NS2-3
    Short name=p23
    EC=3.4.22.-
  7. Serine protease NS3
    EC=3.4.21.98
    EC=3.6.1.15
    EC=3.6.4.13
    Alternative name(s):
    Hepacivirin
    NS3P
    p70
  8. Non-structural protein 4A
    Short name=NS4A
    Alternative name(s):
    p8
  9. Non-structural protein 4B
    Short name=NS4B
    Alternative name(s):
    p27
  10. Non-structural protein 5A
    Short name=NS5A
    Alternative name(s):
    p56
  11. RNA-directed RNA polymerase
    EC=2.7.7.48
    Alternative name(s):
    NS5B
    p68
OrganismHepatitis C virus genotype 2a (isolate HC-J6) (HCV) [Complete proteome]
Taxonomic identifier11113 [NCBI]
Taxonomic lineageViruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Hepacivirus ›
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length3033 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves the host antiviral protein MAVS By similarity. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state.

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 a RNA-dependent RNA polymerase that plays an essential role in the virus replication By similarity.

Catalytic activity

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.

Cofactor

Binds 1 zinc ion per NS3 protease domain By similarity.

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

Enzyme regulation

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.

Subunit structure

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. Ref.2 Ref.3

Subcellular location

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. Ref.5

Core protein p19: Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity Ref.5.

Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein Potential. 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. Ref.5

Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein Potential. 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. Ref.5

p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.5. 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. Ref.5

Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.5.

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. Ref.5

Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Note: Host membrane insertion occurs after processing by the NS3 protease. Ref.5

Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.5.

Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein By similarity. Host cytoplasm › host perinuclear region By similarity. Host mitochondrion By similarity. Note: Host membrane insertion occurs after processing by the NS3 protease. Ref.5

RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Note: Host membrane insertion occurs after processing by the NS3 protease. Ref.5

Domain

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.

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.

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.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the hepacivirus polyprotein family.

Contains 1 helicase ATP-binding domain.

Contains 1 peptidase C18 domain.

Contains 1 peptidase S29 domain.

Contains 1 RdRp catalytic domain.

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.

Ontologies

Keywords
   Biological processActivation 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 IFN-mediated response initiation by virus
Inhibition of host MAVS by virus
Inhibition of host STAT1 by virus
Inhibition of host TRAFs by virus
Inhibition of host innate immune response by virus
Inhibition of host interferon signaling pathway by virus
Interferon antiviral system evasion
Ion transport
Modulation of host cell cycle by virus
Transcription
Transcription regulation
Transport
Viral RNA replication
Viral attachment to host cell
Viral immunoevasion
Viral penetration into host cytoplasm
Virus endocytosis by host
Virus entry into host cell
   Cellular componentHost cell membrane
Host cytoplasm
Host endoplasmic reticulum
Host lipid droplet
Host membrane
Host mitochondrion
Host nucleus
Membrane
Secreted
Viral envelope protein
Virion
   DiseaseOncogene
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Viral nucleoprotein
Zinc
   Molecular functionCapsid protein
Helicase
Hydrolase
Ion channel
Nucleotidyltransferase
Protease
RNA-directed RNA polymerase
Ribonucleoprotein
Serine protease
Thiol protease
Transferase
Viral ion channel
   PTMAcetylation
Disulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

induction by virus of host autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host G1/S transition checkpoint

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host MAVS activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host STAT1 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host TRAF activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon production

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

transformation of host cell by virus

Inferred from electronic annotation. Source: InterPro

viral attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

viral entry into host cell via clathrin-mediated endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

viral genome replication

Inferred from electronic annotation. Source: InterPro

   Cellular_componenthost cell endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell lipid particle

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

ribonucleoprotein complex

Inferred from electronic annotation. Source: UniProtKB-KW

viral capsid

Inferred from electronic annotation. Source: UniProtKB-KW

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent helicase activity

Inferred from electronic annotation. Source: InterPro

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA-directed RNA polymerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

cysteine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type exopeptidase activity

Inferred from electronic annotation. Source: InterPro

structural molecule activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed; by host By similarity
Chain2 – 191190Core protein p21 Potential
PRO_0000037608
Chain2 – 177176Core protein p19 By similarity
PRO_0000037609
Propeptide178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarity
PRO_0000037610
Chain192 – 383192Envelope glycoprotein E1 Potential
PRO_0000037611
Chain384 – 750367Envelope glycoprotein E2 Potential
PRO_0000037612
Chain751 – 81363p7 By similarity
PRO_0000037613
Chain814 – 1030217Protease NS2-3 Potential
PRO_0000037614
Chain1031 – 1661631Serine protease NS3 Potential
PRO_0000037615
Chain1662 – 171554Non-structural protein 4A Potential
PRO_0000037616
Chain1716 – 1976261Non-structural protein 4B Potential
PRO_0000037617
Chain1977 – 2442466Non-structural protein 5A Potential
PRO_0000037618
Chain2443 – 3033591RNA-directed RNA polymerase Potential
PRO_0000037619

Regions

Topological domain2 – 168167Cytoplasmic Potential
Transmembrane169 – 18921Helical; Potential
Topological domain190 – 358169Lumenal Potential
Transmembrane359 – 37921Helical; Potential
Topological domain380 – 729350Lumenal Potential
Transmembrane730 – 75021Helical; Potential
Topological domain751 – 76111Lumenal Potential
Transmembrane762 – 78221Helical; Potential
Topological domain783 – 7864Cytoplasmic Potential
Transmembrane787 – 80721Helical; Potential
Topological domain808 – 81710Lumenal Potential
Transmembrane818 – 83821Helical; Potential
Topological domain839 – 88547Cytoplasmic Potential
Transmembrane886 – 90621Helical; Potential
Topological domain907 – 93226Lumenal Potential
Transmembrane933 – 95321Helical; Potential
Topological domain954 – 1661708Cytoplasmic Potential
Transmembrane1662 – 168221Helical; Potential
Topological domain1683 – 1809127Cytoplasmic Potential
Transmembrane1810 – 183021Helical; Potential
Topological domain1831 – 18322Lumenal Potential
Transmembrane1833 – 185321Helical; Potential
Topological domain18541Cytoplasmic Potential
Transmembrane1855 – 187521Helical; Potential
Topological domain1876 – 188510Lumenal Potential
Transmembrane1886 – 190621Helical; Potential
Topological domain1907 – 197670Cytoplasmic Potential
Intramembrane1977 – 200630 By similarity
Topological domain2007 – 30121006Cytoplasmic Potential
Transmembrane3013 – 303321Helical; By similarity
Domain1221 – 1373153Helicase ATP-binding
Domain2656 – 2774119RdRp catalytic
Nucleotide binding1234 – 12418ATP Potential
Region2 – 5958Interaction with DDX3X By similarity
Region2 – 2322Interaction with STAT1 By similarity
Region122 – 17352Interaction with APOA2 By similarity
Region150 – 15910Mitochondrial targeting signal By similarity
Region164 – 1674Important for lipid droplets localization By similarity
Region265 – 29632Fusion peptide Potential
Region385 – 41127HVR1 By similarity
Region484 – 49613CD81-binding 1 Potential
Region524 – 55532CD81-binding 2 Potential
Region664 – 67512PKR/eIF2-alpha phosphorylation homology domain (PePHD) By similarity
Region1683 – 169412NS3-binding (by NS4A) Potential
Region2124 – 2332209Transcriptional activation Potential
Region2124 – 221289FKBP8-binding Potential
Region2204 – 225047Basal phosphorylation By similarity
Region2214 – 227562PKR-binding Potential
Region2249 – 230658NS4B-binding Potential
Region2351 – 244292Basal phosphorylation By similarity
Motif5 – 139Nuclear localization signal Potential
Motif38 – 436Nuclear localization signal Potential
Motif58 – 647Nuclear localization signal Potential
Motif66 – 716Nuclear localization signal Potential
Motif1320 – 13234DECH box By similarity
Motif2322 – 23254SH3-binding Potential
Motif2327 – 23359Nuclear localization signal Potential
Compositional bias802 – 8076Poly-Leu
Compositional bias1436 – 14394Poly-Val
Compositional bias2282 – 232746Pro-rich
Compositional bias2328 – 23314Poly-Arg
Compositional bias3013 – 30219Poly-Leu

Sites

Active site9561For protease NS2-3 activity; shared with dimeric partner By similarity
Active site9761For protease NS2-3 activity; shared with dimeric partner By similarity
Active site9971For protease NS2-3 activity; shared with dimeric partner By similarity
Active site10871Charge relay system; for serine protease NS3 activity By similarity
Active site11111Charge relay system; for serine protease NS3 activity By similarity
Active site11691Charge relay system; for serine protease NS3 activity By similarity
Metal binding11271Zinc By similarity
Metal binding11291Zinc By similarity
Metal binding11751Zinc By similarity
Metal binding11791Zinc By similarity
Metal binding20151Zinc By similarity
Metal binding20331Zinc By similarity
Metal binding20351Zinc By similarity
Metal binding20561Zinc By similarity
Site177 – 1782Cleavage; by host signal peptidase By similarity
Site191 – 1922Cleavage; by host signal peptidase Potential
Site383 – 3842Cleavage; by host signal peptidase Potential
Site750 – 7512Cleavage; by host signal peptidase By similarity
Site813 – 8142Cleavage; by host signal peptidase By similarity
Site1030 – 10312Cleavage; by protease NS2-3 Potential
Site1661 – 16622Cleavage; by serine protease NS3 Potential
Site1715 – 17162Cleavage; by serine protease NS3 Potential
Site1976 – 19772Cleavage; by serine protease NS3 Potential
Site2442 – 24432Cleavage; by serine protease NS3 Potential

Amino acid modifications

Modified residue21N-acetylserine; by host By similarity
Modified residue531Phosphoserine; by host By similarity
Modified residue991Phosphoserine; by host By similarity
Modified residue1161Phosphoserine; by host PKA By similarity
Modified residue21981Phosphoserine; by host; in p56 By similarity
Modified residue22011Phosphoserine; by host; in p58 By similarity
Modified residue22051Phosphoserine; by host; in p58 By similarity
Modified residue22081Phosphoserine; by host; in p58 By similarity
Lipidation19721S-palmitoyl cysteine; by host By similarity
Lipidation19761S-palmitoyl cysteine; by host By similarity
Glycosylation1961N-linked (GlcNAc...); by host Potential
Glycosylation2091N-linked (GlcNAc...); by host Potential
Glycosylation2341N-linked (GlcNAc...); by host Potential
Glycosylation3051N-linked (GlcNAc...); by host Potential
Glycosylation4171N-linked (GlcNAc...); by host Potential
Glycosylation4231N-linked (GlcNAc...); by host Potential
Glycosylation4301N-linked (GlcNAc...); by host Potential
Glycosylation4481N-linked (GlcNAc...); by host Potential
Glycosylation4771N-linked (GlcNAc...); by host Potential
Glycosylation5341N-linked (GlcNAc...); by host Potential
Glycosylation5421N-linked (GlcNAc...); by host Potential
Glycosylation5581N-linked (GlcNAc...); by host Potential
Glycosylation5781N-linked (GlcNAc...); by host Potential
Glycosylation6271N-linked (GlcNAc...); by host Potential
Glycosylation6491N-linked (GlcNAc...); by host Potential
Disulfide bond2118 ↔ 2166 By similarity

Secondary structure

1 ....................................................................................................... 3033
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P26660 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F957F5C1A273BE9E

FASTA3,033329,169
        10         20         30         40         50         60 
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG 

        70         80         90        100        110        120 
RRQPIPKDRR STGKSWGKPG YPWPLYGNEG LGWAGWLLSP RGSRPSWGPN DPRHRSRNVG 

       130        140        150        160        170        180 
KVIDTLTCGF ADLMGYIPVV GAPLGGVARA LAHGVRVLED GVNFATGNLP GCSFSIFLLA 

       190        200        210        220        230        240 
LLSCITTPVS AAEVKNISTG YMVTNDCTND SITWQLQAAV LHVPGCVPCE KVGNTSRCWI 

       250        260        270        280        290        300 
PVSPNVAVQQ PGALTQGLRT HIDMVVMSAT LCSALYVGDL CGGVMLAAQM FIVSPQHHWF 

       310        320        330        340        350        360 
VQDCNCSIYP GTITGHRMAW DMMMNWSPTA TMILAYAMRV PEVIIDIIGG AHWGVMFGLA 

       370        380        390        400        410        420 
YFSMQGAWAK VVVILLLAAG VDAQTHTVGG STAHNARTLT GMFSLGARQK IQLINTNGSW 

       430        440        450        460        470        480 
HINRTALNCN DSLHTGFLAS LFYTHSFNSS GCPERMSACR SIEAFRVGWG ALQYEDNVTN 

       490        500        510        520        530        540 
PEDMRPYCWH YPPRQCGVVS ASSVCGPVYC FTPSPVVVGT TDRLGAPTYT WGENETDVFL 

       550        560        570        580        590        600 
LNSTRPPQGS WFGCTWMNST GYTKTCGAPP CRIRADFNAS MDLLCPTDCF RKHPDTTYIK 

       610        620        630        640        650        660 
CGSGPWLTPR CLIDYPYRLW HYPCTVNYTI FKIRMYVGGV EHRLTAACNF TRGDRCNLED 

       670        680        690        700        710        720 
RDRSQLSPLL HSTTEWAILP CTYSDLPALS TGLLHLHQNI VDVQFMYGLS PALTKYIVRW 

       730        740        750        760        770        780 
EWVVLLFLLL ADARVCACLW MLILLGQAEA ALEKLVVLHA ASAASCNGFL YFVIFFVAAW 

       790        800        810        820        830        840 
YIKGRVVPLA TYSLTGLWSF GLLLLALPQQ AYAYDASVHG QIGAALLVLI TLFTLTPGYK 

       850        860        870        880        890        900 
TLLSRFLWWL CYLLTLAEAM VQEWAPPMQV RGGRDGIIWA VAIFCPGVVF DITKWLLAVL 

       910        920        930        940        950        960 
GPAYLLKGAL TRVPYFVRAH ALLRMCTMVR HLAGGRYVQM VLLALGRWTG TYIYDHLTPM 

       970        980        990       1000       1010       1020 
SDWAANGLRD LAVAVEPIIF SPMEKKVIVW GAETAACGDI LHGLPVSARL GREVLLGPAD 

      1030       1040       1050       1060       1070       1080 
GYTSKGWSLL APITAYAQQT RGLLGTIVVS MTGRDKTEQA GEIQVLSTVT QSFLGTTISG 

      1090       1100       1110       1120       1130       1140 
VLWTVYHGAG NKTLAGSRGP VTQMYSSAEG DLVGWPSPPG TKSLEPCTCG AVDLYLVTRN 

      1150       1160       1170       1180       1190       1200 
ADVIPARRRG DKRGALLSPR PLSTLKGSSG GPVLCPRGHA VGVFRAAVCS RGVAKSIDFI 

      1210       1220       1230       1240       1250       1260 
PVETLDIVTR SPTFSDNSTP PAVPQTYQVG YLHAPTGSGK STKVPVAYAA QGYKVLVLNP 

      1270       1280       1290       1300       1310       1320 
SVAATLGFGA YLSKAHGINP NIRTGVRTVT TGAPITYSTY GKFLADGGCA GGAYDIIICD 

      1330       1340       1350       1360       1370       1380 
ECHAVDSTTI LGIGTVLDQA ETAGVRLTVL ATATPPGSVT TPHPNIEEVA LGQEGEIPFY 

      1390       1400       1410       1420       1430       1440 
GRAIPLSYIK GGRHLIFCHS KKKCDELAAA LRGMGLNAVA YYRGLDVSVI PTQGDVVVVA 

      1450       1460       1470       1480       1490       1500 
TDALMTGFTG DFDSVIDCNV AVTQVVDFSL DPTFTITTQT VPQDAVSRSQ RRGRTGRGRL 

      1510       1520       1530       1540       1550       1560 
GIYRYVSTGE RASGMFDSVV LCECYDAGAA WYELTPAETT VRLRAYFNTP GLPVCQDHLE 

      1570       1580       1590       1600       1610       1620 
FWEAVFTGLT HIDAHFLSQT KQSGENFAYL TAYQATVCAR AKAPPPSWDV MWKCLTRLKP 

      1630       1640       1650       1660       1670       1680 
TLVGPTPLLY RLGSVTNEVT LTHPVTKYIA TCMQADLEVM TSTWVLAGGV LAAVAAYCLA 

      1690       1700       1710       1720       1730       1740 
TGCVCIIGRL HVNQRAVVAP DKEVLYEAFD EMEECASRAA LIEEGQRIAE MLKSKIQGLL 

      1750       1760       1770       1780       1790       1800 
QQASKQAQDI QPAVQASWPK VEQFWAKHMW NFISGIQYLA GLSTLPGNPA VASMMAFSAA 

      1810       1820       1830       1840       1850       1860 
LTSPLSTSTT ILLNILGGWL ASQIAPPAGA TGFVVSGLVG AAVGSIGLGK VLVDILAGYG 

      1870       1880       1890       1900       1910       1920 
AGISGALVAF KIMSGEKPSM EDVVNLLPGI LSPGALVVGV ICAAILRRHV GPGEGAVQWM 

      1930       1940       1950       1960       1970       1980 
NRLIAFASRG NHVAPTHYVT ESDASQRVTQ LLGSLTITSL LRRLHNWITE DCPIPCSGSW 

      1990       2000       2010       2020       2030       2040 
LRDVWDWVCT ILTDFKNWLT SKLFPKMPGL PFISCQKGYK GVWAGTGIMT TRCPCGANIS 

      2050       2060       2070       2080       2090       2100 
GNVRLGSMRI TGPKTCMNIW QGTFPINCYT EGQCVPKPAP NFKIAIWRVA ASEYAEVTQH 

      2110       2120       2130       2140       2150       2160 
GSYHYITGLT TDNLKVPCQL PSPEFFSWVD GVQIHRFAPI PKPFFRDEVS FCVGLNSFVV 

      2170       2180       2190       2200       2210       2220 
GSQLPCDPEP DTDVLTSMLT DPSHITAETA ARRLARGSPP SEASSSASQL SAPSLRATCT 

      2230       2240       2250       2260       2270       2280 
THGKAYDVDM VDANLFMGGD VTRIESESKV VVLDSLDPMV EERSDLEPSI PSEYMLPKKR 

      2290       2300       2310       2320       2330       2340 
FPPALPAWAR PDYNPPLVES WKRPDYQPAT VAGCALPPPK KTPTPPPRRR RTVGLSESSI 

      2350       2360       2370       2380       2390       2400 
ADALQQLAIK SFGQPPPSGD SGLSTGADAA DSGSRTPPDE LALSETGSIS SMPPLEGEPG 

      2410       2420       2430       2440       2450       2460 
DPDLEPEQVE LQPPPQGGVV TPGSGSGSWS TCSEEDDSVV CCSMSYSWTG ALITPCSPEE 

      2470       2480       2490       2500       2510       2520 
EKLPINPLSN SLLRYHNKVY CTTSKSASLR AKKVTFDRMQ ALDAHYDSVL KDIKLAASKV 

      2530       2540       2550       2560       2570       2580 
TARLLTLEEA CQLTPPHSAR SKYGFGAKEV RSLSGRAVNH IKSVWKDLLE DTQTPIPTTI 

      2590       2600       2610       2620       2630       2640 
MAKNEVFCVD PTKGGKKAAR LIVYPDLGVR VCEKMALYDI TQKLPQAVMG ASYGFQYSPA 

      2650       2660       2670       2680       2690       2700 
QRVEFLLKAW AEKKDPMGFS YDTRCFDSTV TERDIRTEES IYRACSLPEE AHTAIHSLTE 

      2710       2720       2730       2740       2750       2760 
RLYVGGPMFN SKGQTCGYRR CRASGVLTTS MGNTITCYVK ALAACKAAGI IAPTMLVCGD 

      2770       2780       2790       2800       2810       2820 
DLVVISESQG TEEDERNLRA FTEAMTRYSA PPGDPPRPEY DLELITSCSS NVSVALGPQG 

      2830       2840       2850       2860       2870       2880 
RRRYYLTRDP TTPIARAAWE TVRHSPVNSW LGNIIQYAPT IWARMVLMTH FFSILMAQDT 

      2890       2900       2910       2920       2930       2940 
LDQNLNFEMY GAVYSVSPLD LPAIIERLHG LDAFSLHTYT PHELTRVASA LRKLGAPPLR 

      2950       2960       2970       2980       2990       3000 
AWKSRARAVR ASLISRGGRA AVCGRYLFNW AVKTKLKLTP LPEARLLDLS SWFTVGAGGG 

      3010       3020       3030 
DIYHSVSRAR PRLLLLGLLL LFVGVGLFLL PAR

« Hide

References

[1]"Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions."
Okamoto H., Okada S., Sugiyama Y., Kurai K., Lizuka H., Machida A., Miyakawa Y., Mayumi M.
J. Gen. Virol. 72:2697-2704(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"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.
[3]"Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry."
Evans M.J., von Hahn T., Tscherne D.M., Syder A.J., Panis M., Wolk B., Hatziioannou T., McKeating J.A., Bieniasz P.D., Rice C.M.
Nature 446:801-805(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CLDN1.
[4]"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.
[5]"Structural biology of hepatitis C virus."
Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M.
Hepatology 39:5-19(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, SUBCELLULAR LOCATION.
[6]"Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors."
Biswal B.K., Cherney M.M., Wang M., Chan L., Yannopoulos C.G., Bilimoria D., Nicolas O., Bedard J., James M.N.G.
J. Biol. Chem. 280:18202-18210(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2443-3012.
+Additional computationally mapped references.

Web resources

euHCVdb

The European HCV database

Virus Pathogen Resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		D00944 Genomic RNA. Translation: BAA00792.1.
PIRJQ1303.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YUYX-ray1.90A2443-3012[»]
1YV2X-ray2.50A2443-3012[»]
1YVXX-ray2.00A2443-3012[»]
1YVZX-ray2.20A2443-3012[»]
2XWHX-ray1.80A2443-3005[»]
4ADPX-ray1.90A2443-3012[»]
ProteinModelPortalP26660.
SMRP26660. Positions 2-45, 906-1030, 1033-1661, 1977-2007, 2012-2174, 2443-2990.
ModBaseSearch...

Protein-protein interaction databases

IntActP26660. 5 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

euHCVdbD00944.

Family and domain databases

InterProIPR011492. 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]
PfamPF07652. 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]
ProDomPD001388. HCV_env. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00487. DEXDc. 1 hit.
[Graphical view]
SUPFAMSSF50494. Pept_Ser_Cys. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. False negative.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP26660.

Entry information

Entry namePOLG_HCVJ6
AccessionPrimary (citable) accession number: P26660
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: May 29, 2013
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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