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P26663 (POLG_HCVBK) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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 1b (isolate BK) (HCV) [Complete proteome]
Taxonomic identifier11105 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length3010 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/Sp110bin 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. Ref.5 Ref.14 Ref.15

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. Ref.5 Ref.14 Ref.15

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. Ref.5 Ref.14 Ref.15

Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation By similarity. Ref.5 Ref.14 Ref.15

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. Ref.5 Ref.14 Ref.15

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. Ref.5 Ref.14 Ref.15

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. Ref.5 Ref.14 Ref.15

NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication By similarity. Ref.5 Ref.14 Ref.15

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, 1,10-phenanthroline, iodocetamide and N-ethylmaleimide. According to Ref.4, completely inhibited by the serine protease inhibitors TLCK and TPCK. According to Ref.3, almost completely inhibited by TPCK and slightly inhibited by TLCK. Not inhibited by antipain, aprotinin, E64, PMSF and pepstatin. Also inhibited by NS2-3 and NS4A derived peptides. Serine protease NS3 is also activated by zinc ions.

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.6 Ref.9 Ref.13 Ref.14 Ref.18

Subcellular location

Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Host mitochondrion membrane; Single-pass type I membrane protein. Host lipid droplet. Note: The C-terminal transmembrane domain of core protein p21 contains an ER signal leading the nascent polyprotein to the ER membrane. Only a minor proportion of core protein is present in the nucleus and an unknown proportion is secreted. Ref.3 Ref.15 Ref.17

Core protein p19: Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity Ref.3 Ref.15 Ref.17.

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.3 Ref.15 Ref.17

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.3 Ref.15 Ref.17

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. Ref.3 Ref.15 Ref.17

Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.3 Ref.15 Ref.17.

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.3 Ref.15 Ref.17

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.3 Ref.15 Ref.17

Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.3 Ref.15 Ref.17.

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. Ref.3 Ref.15 Ref.17

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.3 Ref.15 Ref.17

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 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. Ref.10 Ref.12

The N-terminus of NS5A acts as membrane anchor. The central part of NS5A contains a variable region called interferon sensitivity determining region (ISDR) and seems to be intrinsically disordered and interacts with NS5B and host PKR By similarity. The C-terminus of NS5A contains a variable region called variable region 3 (V3). ISDR and V3 may be involved in sensitivity and/or resistance to IFN-alpha therapy. Ref.10 Ref.12

The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases. Ref.10 Ref.12

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. Ref.10 Ref.12

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. Ref.11

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. Ref.11

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 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
   Cellular componentCapsid protein
Host cell membrane
Host cytoplasm
Host endoplasmic reticulum
Host lipid droplet
Host membrane
Host mitochondrion
Host nucleus
Membrane
Secreted
Viral envelope protein
Virion
   DiseaseOncogene
   DomainSH3-binding
Transmembrane
Transmembrane helix
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Viral nucleoprotein
Zinc
   Molecular functionHelicase
Hydrolase
Ion channel
Nucleotidyltransferase
Protease
Ribonucleoprotein
RNA-directed RNA polymerase
Serine protease
Thiol protease
Transferase
Viral ion channel
   PTMAcetylation
Disulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

clathrin-mediated endocytosis of virus by host cell

Inferred from electronic annotation. Source: UniProtKB-KW

fusion of virus membrane with host endosome membrane

Inferred from electronic annotation. Source: UniProtKB-KW

induction by virus of host autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host G1/S transition checkpoint

Inferred from electronic annotation. Source: UniProtKB-KW

pore formation by virus in membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

protein oligomerization

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of transcription, DNA-templated

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-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transformation of host cell by virus

Inferred from electronic annotation. Source: InterPro

viral RNA genome replication

Inferred from electronic annotation. Source: InterPro

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   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 component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

integral to membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

ribonucleoprotein complex

Inferred from electronic annotation. Source: UniProtKB-KW

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

viral nucleocapsid

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

identical protein binding

Inferred from physical interaction PubMed 18179252. Source: IntAct

ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15767257PubMed 18519040PubMed 7853516PubMed 9188558Ref.20PubMed 9827557PubMed 18179252. Source: IntAct

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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Q9WMX25EBI-6874437,EBI-6863741From a different organism.
PkmP524803EBI-6857429,EBI-647785From a different organism.
Sos1Q622452EBI-6857429,EBI-1693From a different organism.
TP53P046379EBI-6838571,EBI-366083From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed; by host By similarity
Chain2 – 191190Core protein p21 Potential
PRO_0000037529
Chain2 – 177176Core protein p19 By similarity
PRO_0000037530
Propeptide178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarity
PRO_0000037531
Chain192 – 383192Envelope glycoprotein E1 Potential
PRO_0000037532
Chain384 – 746363Envelope glycoprotein E2 Potential
PRO_0000037533
Chain747 – 80963p7 By similarity
PRO_0000037534
Chain810 – 1026217Protease NS2-3 Potential
PRO_0000037535
Chain1027 – 1657631Serine protease NS3
PRO_0000037536
Chain1658 – 171154Non-structural protein 4A
PRO_0000037537
Chain1712 – 1972261Non-structural protein 4B
PRO_0000037538
Chain1973 – 2419447Non-structural protein 5A
PRO_0000037539
Chain2420 – 3010591RNA-directed RNA polymerase
PRO_0000037540

Regions

Topological domain2 – 168167Cytoplasmic Potential
Transmembrane169 – 18921Helical; Potential
Topological domain190 – 358169Lumenal Potential
Transmembrane359 – 37921Helical; Potential
Topological domain380 – 725346Lumenal Potential
Transmembrane726 – 74621Helical; Potential
Topological domain747 – 75711Lumenal Potential
Transmembrane758 – 77821Helical; Potential
Topological domain779 – 7824Cytoplasmic Potential
Transmembrane783 – 80321Helical; Potential
Topological domain804 – 81310Lumenal Potential
Transmembrane814 – 83421Helical; Potential
Topological domain835 – 88147Cytoplasmic Potential
Transmembrane882 – 90221Helical; Potential
Topological domain903 – 92826Lumenal Potential
Transmembrane929 – 94921Helical; Potential
Topological domain950 – 1657708Cytoplasmic Potential
Transmembrane1658 – 167821Helical; Potential
Topological domain1679 – 1805127Cytoplasmic Potential
Transmembrane1806 – 182621Helical; Potential
Topological domain1827 – 18282Lumenal Potential
Transmembrane1829 – 184921Helical; Potential
Topological domain18501Cytoplasmic Potential
Transmembrane1851 – 187121Helical; Potential
Topological domain1872 – 188110Lumenal Potential
Transmembrane1882 – 190221Helical; Potential
Topological domain1903 – 197270Cytoplasmic Potential
Intramembrane1973 – 200230 By similarity
Topological domain2003 – 2989987Cytoplasmic Potential
Transmembrane2990 – 301021Helical; By similarity
Domain903 – 1026124Peptidase C18
Domain1217 – 1369153Helicase ATP-binding
Domain2633 – 2751119RdRp catalytic
Nucleotide binding1230 – 12378ATP Potential
Region2 – 5958Interaction with DDX3X By similarity
Region2 – 2322Interaction with STAT1 By similarity
Region122 – 17352Interaction with APOA2 By similarity
Region148 – 23689Interaction with FKBP8
Region150 – 15910Mitochondrial targeting signal By similarity
Region164 – 1674Important for lipid droplets localization By similarity
Region265 – 29632Fusion peptide Potential
Region385 – 41127HVR1
Region475 – 4817HVR2
Region482 – 49413CD81-binding 1 Potential
Region522 – 55332CD81-binding 2 Potential
Region660 – 67112PKR/eIF2-alpha phosphorylation homology domain (PePHD)
Region1679 – 169012NS3-binding (by NS4A) Potential
Region2120 – 2332213Transcriptional activation Potential
Region2120 – 220889FKBP8-binding Potential
Region2200 – 225051Basal phosphorylation By similarity
Region2210 – 227566PKR-binding Potential
Region2210 – 224940ISDR
Region2249 – 230658NS4B-binding Potential
Region2351 – 241969Basal phosphorylation By similarity
Region2354 – 237724V3
Motif5 – 139Nuclear localization signal Potential
Motif38 – 436Nuclear localization signal Potential
Motif58 – 647Nuclear localization signal Potential
Motif66 – 716Nuclear localization signal Potential
Motif1316 – 13194DECH box
Motif2322 – 23254SH3-binding Potential
Motif2327 – 23359Nuclear localization signal Potential
Compositional bias796 – 8038Poly-Leu
Compositional bias1432 – 14354Poly-Val
Compositional bias2282 – 232746Pro-rich
Compositional bias2995 – 29984Poly-Leu

Sites

Active site9521For protease NS2-3 activity; shared with dimeric partner By similarity
Active site9721For protease NS2-3 activity; shared with dimeric partner By similarity
Active site9931For protease NS2-3 activity; shared with dimeric partner By similarity
Active site10831Charge relay system; for serine protease NS3 activity By similarity
Active site11071Charge relay system; for serine protease NS3 activity By similarity
Active site11651Charge relay system; for serine protease NS3 activity By similarity
Metal binding11231Zinc
Metal binding11251Zinc
Metal binding11711Zinc
Metal binding11751Zinc
Metal binding20111Zinc By similarity
Metal binding20291Zinc By similarity
Metal binding20311Zinc By similarity
Metal binding20521Zinc By similarity
Site177 – 1782Cleavage; by host signal peptidase By similarity
Site191 – 1922Cleavage; by host signal peptidase Potential
Site383 – 3842Cleavage; by host signal peptidase Potential
Site746 – 7472Cleavage; by host signal peptidase By similarity
Site809 – 8102Cleavage; by host signal peptidase By similarity
Site1026 – 10272Cleavage; by protease NS2-3 Potential
Site1657 – 16582Cleavage; by serine protease NS3 Potential
Site1711 – 17122Cleavage; by serine protease NS3 Potential
Site1972 – 19732Cleavage; by serine protease NS3 Potential
Site2419 – 24202Cleavage; 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 residue21941Phosphoserine; by host; in p56 Probable
Modified residue21971Phosphoserine; by host; in p58 By similarity
Modified residue22011Phosphoserine; by host; in p58 By similarity
Modified residue22041Phosphoserine; by host; in p58 By similarity
Lipidation19681S-palmitoyl cysteine; by host By similarity
Lipidation19721S-palmitoyl cysteine; by host By similarity
Glycosylation1961N-linked (GlcNAc...); by host Potential
Glycosylation2091N-linked (GlcNAc...); by host Potential
Glycosylation2341N-linked (GlcNAc...); by host Potential
Glycosylation2501N-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
Glycosylation5321N-linked (GlcNAc...); by host Potential
Glycosylation5401N-linked (GlcNAc...); by host Potential
Glycosylation5561N-linked (GlcNAc...); by host Potential
Glycosylation5761N-linked (GlcNAc...); by host Potential
Glycosylation6231N-linked (GlcNAc...); by host Potential
Glycosylation6451N-linked (GlcNAc...); by host Potential
Disulfide bond2114 ↔ 2162 By similarity

Experimental info

Mutagenesis21941S → A: Loss of phosphorylation. Ref.7
Mutagenesis23221P → A: Complete loss of binding to GRB2. Ref.6
Mutagenesis23231P → A: Complete loss of binding to GRB2. Ref.6
Mutagenesis23261P → A: Complete loss of binding to GRB2. Ref.6

Secondary structure

............................................................................................................................................................................................................................................. 3010
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P26663 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F8422D5ECCFDFD9C

FASTA3,010327,194
        10         20         30         40         50         60 
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRAPR KTSERSQPRG 

        70         80         90        100        110        120 
RRQPIPKARR PEGRTWAQPG YPWPLYGNEG LGWAGWLLSP RGSRPSWGPT DPRRRSRNLG 

       130        140        150        160        170        180 
KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA 

       190        200        210        220        230        240 
LLSCLTTPAS AYEVHNVSGI YHVTNDCSNA SIVYEAADLI MHTPGCVPCV REGNSSRCWV 

       250        260        270        280        290        300 
ALTPTLAARN VTIPTTTIRR HVDLLVGAAA FCSAMYVGDL CGSVFLVSQL FTFSPRRHVT 

       310        320        330        340        350        360 
LQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG AHWGVLAGLA 

       370        380        390        400        410        420 
YYSMAGNWAK VLIVMLLFAG VDGDTHVTGG AQAKTTNRLV SMFASGPSQK IQLINTNGSW 

       430        440        450        460        470        480 
HINRTALNCN DSLQTGFLAA LFYTHSFNSS GCPERMAQCR TIDKFDQGWG PITYAESSRS 

       490        500        510        520        530        540 
DQRPYCWHYP PPQCTIVPAS EVCGPVYCFT PSPVVVGTTD RFGVPTYRWG ENETDVLLLN 

       550        560        570        580        590        600 
NTRPPQGNWF GCTWMNSTGF TKTCGGPPCN IGGVGNNTLT CPTDCFRKHP EATYTKCGSG 

       610        620        630        640        650        660 
PWLTPRCMVD YPYRLWHYPC TVNFTIFKVR MYVGGVEHRL NAACNWTRGE RCDLEDRDRP 

       670        680        690        700        710        720 
ELSPLLLSTT EWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGIGSAVV SFAIKWEYVL 

       730        740        750        760        770        780 
LLFLLLADAR VCACLWMMLL IAQAEAALEN LVVLNSASVA GAHGILSFLV FFCAAWYIKG 

       790        800        810        820        830        840 
RLVPGATYAL YGVWPLLLLL LALPPRAYAM DREMAASCGG AVFVGLVLLT LSPYYKVFLA 

       850        860        870        880        890        900 
RLIWWLQYFT TRAEADLHVW IPPLNARGGR DAIILLMCAV HPELIFDITK LLIAILGPLM 

       910        920        930        940        950        960 
VLQAGITRVP YFVRAQGLIH ACMLVRKVAG GHYVQMAFMK LGALTGTYIY NHLTPLRDWP 

       970        980        990       1000       1010       1020 
RAGLRDLAVA VEPVVFSDME TKIITWGADT AACGDIILGL PVSARRGKEI LLGPADSLEG 

      1030       1040       1050       1060       1070       1080 
RGLRLLAPIT AYSQQTRGLL GCIITSLTGR DKNQVEGEVQ VVSTATQSFL ATCVNGVCWT 

      1090       1100       1110       1120       1130       1140 
VYHGAGSKTL AAPKGPITQM YTNVDQDLVG WPKPPGARSL TPCTCGSSDL YLVTRHADVI 

      1150       1160       1170       1180       1190       1200 
PVRRRGDSRG SLLSPRPVSY LKGSSGGPLL CPFGHAVGIF RAAVCTRGVA KAVDFVPVES 

      1210       1220       1230       1240       1250       1260 
METTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK VLVLNPSVAA 

      1270       1280       1290       1300       1310       1320 
TLGFGAYMSK AHGIDPNIRT GVRTITTGAP VTYSTYGKFL ADGGCSGGAY DIIICDECHS 

      1330       1340       1350       1360       1370       1380 
TDSTTILGIG TVLDQAETAG ARLVVLATAT PPGSVTVPHP NIEEVALSNT GEIPFYGKAI 

      1390       1400       1410       1420       1430       1440 
PIEAIRGGRH LIFCHSKKKC DELAAKLSGL GINAVAYYRG LDVSVIPTIG DVVVVATDAL 

      1450       1460       1470       1480       1490       1500 
MTGYTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRRGIYR 

      1510       1520       1530       1540       1550       1560 
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV CQDHLEFWES 

      1570       1580       1590       1600       1610       1620 
VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP PPSWDQMWKC LIRLKPTLHG 

      1630       1640       1650       1660       1670       1680 
PTPLLYRLGA VQNEVTLTHP ITKYIMACMS ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV 

      1690       1700       1710       1720       1730       1740 
VIVGRIILSG RPAIVPDREL LYQEFDEMEE CASHLPYIEQ GMQLAEQFKQ KALGLLQTAT 

      1750       1760       1770       1780       1790       1800 
KQAEAAAPVV ESKWRALETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP 

      1810       1820       1830       1840       1850       1860 
LTTQSTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD ILAGYGAGVA 

      1870       1880       1890       1900       1910       1920 
GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA ILRRHVGPGE GAVQWMNRLI 

      1930       1940       1950       1960       1970       1980 
AFASRGNHVS PTHYVPESDA AARVTQILSS LTITQLLKRL HQWINEDCST PCSGSWLRDV 

      1990       2000       2010       2020       2030       2040 
WDWICTVLTD FKTWLQSKLL PQLPGVPFFS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK 

      2050       2060       2070       2080       2090       2100 
NGSMRIVGPK TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH 

      2110       2120       2130       2140       2150       2160 
YVTGMTTDNV KCPCQVPAPE FFSEVDGVRL HRYAPACRPL LREEVTFQVG LNQYLVGSQL 

      2170       2180       2190       2200       2210       2220 
PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS SSASQLSAPS LKATCTTHHV 

      2230       2240       2250       2260       2270       2280 
SPDADLIEAN LLWRQEMGGN ITRVESENKV VVLDSFDPLR AEEDEREVSV PAEILRKSKK 

      2290       2300       2310       2320       2330       2340 
FPAAMPIWAR PDYNPPLLES WKDPDYVPPV VHGCPLPPIK APPIPPPRRK RTVVLTESSV 

      2350       2360       2370       2380       2390       2400 
SSALAELATK TFGSSESSAV DSGTATALPD QASDDGDKGS DVESYSSMPP LEGEPGDPDL 

      2410       2420       2430       2440       2450       2460 
SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEESKL PINALSNSLL RHHNMVYATT 

      2470       2480       2490       2500       2510       2520 
SRSAGLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK LLSVEEACKL TPPHSAKSKF 

      2530       2540       2550       2560       2570       2580 
GYGAKDVRNL SSKAVNHIHS VWKDLLEDTV TPIDTTIMAK NEVFCVQPEK GGRKPARLIV 

      2590       2600       2610       2620       2630       2640 
FPDLGVRVCE KMALYDVVST LPQVVMGSSY GFQYSPGQRV EFLVNTWKSK KNPMGFSYDT 

      2650       2660       2670       2680       2690       2700 
RCFDSTVTEN DIRVEESIYQ CCDLAPEARQ AIKSLTERLY IGGPLTNSKG QNCGYRRCRA 

      2710       2720       2730       2740       2750       2760 
SGVLTTSCGN TLTCYLKASA ACRAAKLQDC TMLVNGDDLV VICESAGTQE DAASLRVFTE 

      2770       2780       2790       2800       2810       2820 
AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV YYLTRDPTTP LARAAWETAR 

      2830       2840       2850       2860       2870       2880 
HTPVNSWLGN IIMYAPTLWA RMILMTHFFS ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ 

      2890       2900       2910       2920       2930       2940 
IIERLHGLSA FSLHSYSPGE INRVASCLRK LGVPPLRVWR HRARSVRARL LSQGGRAATC 

      2950       2960       2970       2980       2990       3000 
GKYLFNWAVK TKLKLTPIPA ASRLDLSGWF VAGYSGGDIY HSLSRARPRW FMLCLLLLSV 

      3010 
GVGIYLLPNR 

« Hide

References

[1]"Structure and organization of the hepatitis C virus genome isolated from human carriers."
Takamizawa A., Mori C., Fuke I., Manabe S., Murakami S., Fujita J., Onishi E., Andoh T., Yoshida I., Okayama H.
J. Virol. 65:1105-1113(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Non-structural protein 3 of hepatitis C virus inhibits phosphorylation mediated by cAMP-dependent protein kinase."
Borowski P., Heiland M., Oehlmann K., Becker B., Korneteky L.
Eur. J. Biochem. 237:611-618(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1487-1500.
[3]"Biosynthesis and biochemical properties of the hepatitis C virus core protein."
Santolini E., Migliaccio G., La Monica N.
J. Virol. 68:3631-3641(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, RNA-BINDING ACTIVITY OF CORE PROTEIN.
[4]"In vitro study of the NS2-3 protease of hepatitis C virus."
Pieroni L., Santolini E., Fipaldini C., Pacini L., Migliaccio G., La Monica N.
J. Virol. 71:6373-6380(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF PROTEASE NS2-3.
[5]"Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation."
Gale M.J. Jr., Blakely C.M., Kwieciszewski B., Tan S.-L., Dossett M., Tang N.M., Korth M.J., Polyak S.J., Gretch D.R., Katze M.G.
Mol. Cell. Biol. 18:5208-5218(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF NS5A.
[6]"NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling."
Tan S.-L., Nakao H., He Y., Vijaysri S., Neddermann P., Jacobs B.L., Mayer B.J., Katze M.G.
Proc. Natl. Acad. Sci. U.S.A. 96:5533-5538(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH HUMAN GRB2, MUTAGENESIS OF PRO-2322; PRO-2323 AND PRO-2326.
[7]"Ser(2194) is a highly conserved major phosphorylation site of the hepatitis C virus nonstructural protein NS5A."
Katze M.G., Kwieciszewski B., Goodlett D.R., Blakely C.M., Neddermann P., Tan S.-L., Aebersold R.
Virology 278:501-513(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-2194.
[8]"In vitro characterization of a purified NS2/3 protease variant of hepatitis C virus."
Thibeault D., Maurice R., Pilote L., Lamarre D., Pause A.
J. Biol. Chem. 276:46678-46684(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF PROTEASE NS2-3.
[9]"Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase."
He Y., Nakao H., Tan S.-L., Polyak S.J., Neddermann P., Vijaysri S., Jacobs B.L., Katze M.G.
J. Virol. 76:9207-9217(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH HUMAN PIK3R1.
[10]"Mutations within the CD81-binding sites and hypervariable region 2 of the envelope 2 protein: correlation with treatment response in hepatitis C virus-infected patients."
Hofmann W.P., Sarrazin C., Kronenberger B., Schonberger B., Bruch K., Zeuzem S.
J. Infect. Dis. 187:982-987(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS CD81-BINDING AND HVR2.
[11]"High-throughput screening of the yeast kinome: identification of human serine/threonine protein kinases that phosphorylate the hepatitis C virus NS5A protein."
Coito C., Diamond D.L., Neddermann P., Korth M.J., Katze M.G.
J. Virol. 78:3502-3513(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION OF NS5A.
[12]"Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy."
Vuillermoz I., Khattab E., Sablon E., Ottevaere I., Durantel D., Vieux C., Trepo C., Zoulim F.
J. Med. Virol. 74:41-53(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS ISDR AND V3 REGIONS.
[13]"Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus."
Ahn J., Chung K.-S., Kim D.-U., Won M., Kim L., Kim K.-S., Nam M., Choi S.-J., Kim H.-C., Yoon M., Chae S.-K., Hoe K.-L.
J. Biochem. Mol. Biol. 37:741-748(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH CELLULAR PROTEINS.
[14]"The SH3 binding motif of HCV NS5A protein interacts with Bin1 and is important for apoptosis and infectivity."
Nanda S.K., Herion D., Liang T.J.
Gastroenterology 130:794-809(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH HUMAN BIN1, FUNCTION OF NS5A.
[15]"Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core."
Jackel-Cram C., Babiuk L.A., Liu Q.
J. Hepatol. 46:999-1008(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN, FUNCTION OF CORE PROTEIN.
[16]"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.
[17]"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.
[18]"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.
[19]"The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site."
Love R.A., Parge H.E., Wickersham J.A., Hostomsky Z., Habuka N., Moomaw E.W., Adachi T., Hostomska Z.
Cell 87:331-342(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1027-1215.
[20]"Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2-A resolution structure in a hexagonal crystal form."
Yan Y., Li Y., Munshi S., Sardana V., Cole J.L., Sardana M., Steinkuehler C., Tomei L., de Francesco R., Kuo L.C., Chen Z.
Protein Sci. 7:837-847(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1027-1206 AND 1678-1691.
[21]"Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A feasible mechanism of unwinding duplex RNA."
Cho H.-S., Ha N.-C., Kang L.-W., Chung K.M., Back S.H., Jang S.K., Oh B.-H.
J. Biol. Chem. 273:15045-15052(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1216-1650.
[22]"Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase."
Yao N., Reichert P., Taremi S.S., Prosise W.W., Weber P.C.
Structure 7:1353-1363(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1013-1657.
[23]"The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism."
Barbato G., Cicero D.O., Nardi M.C., Steinkuehler C., Cortese R., De Francesco R., Bazzo R.
J. Mol. Biol. 289:371-384(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1027-1206.
[24]"Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus."
Bressanelli S., Tomei L., Roussel A., Incitti I., Vitale R.L., Mathieu M., De Francesco R., Rey F.A.
Proc. Natl. Acad. Sci. U.S.A. 96:13034-13039(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2420-2950.
[25]"Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site."
Lesburg C.A., Cable M.B., Ferrari E., Hong Z., Mannarino A.F., Weber P.C.
Nat. Struct. Biol. 6:937-943(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2414-2989.
[26]"Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus."
Ago H., Adachi T., Yoshida A., Yamamoto M., Habuka N., Yatsunami K., Miyano M.
Structure 7:1417-1426(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2420-2999.
[27]"Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides."
Bressanelli S., Tomei L., Rey F.A., De Francesco R.
J. Virol. 76:3482-3492(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2420-2955.
[28]"Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition."
Wang M., Ng K.K.-S., Cherney M.M., Chan L., Yannopoulos C.G., Bedard J., Morin N., Nguyen-Ba N., Alaoui-Ismaili M.H., Bethell R.C., James M.N.G.
J. Biol. Chem. 278:9489-9495(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2420-2989 IN COMPLEX WITH A NON-NUCLEOSIDE INHIBITOR.
[29]"Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme."
Love R.A., Parge H.E., Yu X., Hickey M.J., Diehl W., Gao J., Wriggers H., Ekker A., Wang L., Thomson J.A., Dragovich P.S., Fuhrman S.A.
J. Virol. 77:7575-7581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2420-2995 IN COMPLEX WITH AN INHIBITOR.
+Additional computationally mapped references.

Web resources

euHCVdb

The European HCV database

Virus Pathogen Resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M58335 Genomic RNA. Translation: AAA72945.1.
PIRGNWVTC. A38465.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A1QX-ray2.40A/B/C1027-1215[»]
1BT7NMR-A1027-1206[»]
1C2PX-ray1.90A/B2422-2989[»]
1CSJX-ray2.80A/B2420-2950[»]
1CU1X-ray2.50A/B1029-1657[»]
1GX5X-ray1.70A2420-2955[»]
1GX6X-ray1.85A2420-2950[»]
1JXPX-ray2.20A/B1027-1206[»]
C/D1678-1691[»]
1NHUX-ray2.00A/B2420-2989[»]
1NHVX-ray2.90A/B2420-2989[»]
1NS3X-ray2.80A/B1029-1206[»]
C/D1678-1689[»]
1OS5X-ray2.20A2420-2989[»]
1QUVX-ray2.50A2420-2989[»]
2AWZX-ray2.15A/B2420-2989[»]
2AX0X-ray2.00A/B2420-2989[»]
2AX1X-ray2.10A/B2420-2989[»]
2BRKX-ray2.30A2420-2955[»]
2BRLX-ray2.40A2420-2955[»]
2DXSX-ray2.20A/B2420-2963[»]
2GIQX-ray1.65A/B2421-2981[»]
2GIRX-ray1.90A/B2421-2981[»]
2HAIX-ray1.58A2420-2988[»]
2HWHX-ray2.30A/B2422-2989[»]
2HWIX-ray2.00A/B2422-2989[»]
2I1RX-ray2.20A/B2422-2989[»]
2JC0X-ray2.20A/B2420-2989[»]
2JC1X-ray2.00A/B2420-2989[»]
2O5DX-ray2.20A/B2422-2989[»]
2WCXX-ray2.00A2420-2955[»]
2WHOX-ray2.00A/B2420-2955[»]
2WRMX-ray1.95A2420-2955[»]
2XWYX-ray2.53A2420-2955[»]
2ZKUX-ray1.95A/B/C/D2420-2989[»]
3BR9X-ray2.30A/B2420-2989[»]
3BSAX-ray2.30A/B2420-2989[»]
3BSCX-ray2.65A/B2420-2989[»]
3CDEX-ray2.10A/B2420-2989[»]
3CIZX-ray1.87A/B2421-2989[»]
3CJ0X-ray1.90A/B2421-2989[»]
3CJ2X-ray1.75A/B2421-2989[»]
3CJ3X-ray1.87A/B2421-2989[»]
3CJ4X-ray2.07A/B2421-2989[»]
3CJ5X-ray1.92A/B2421-2989[»]
3CO9X-ray2.10A/B2420-2989[»]
3CVKX-ray2.31A/B2420-2989[»]
3CWJX-ray2.40A/B2420-2989[»]
3D28X-ray2.30A/B2420-2989[»]
3D5MX-ray2.20A/B2420-2989[»]
3E51X-ray1.90A/B2420-2989[»]
3FQKX-ray2.20A/B2421-2989[»]
3FRZX-ray1.86A2420-2989[»]
3G86X-ray2.20A/B2421-2989[»]
3GYNX-ray2.15A/B2420-2989[»]
3H2LX-ray1.90A/B2420-2989[»]
3H59X-ray2.10A/B2421-2989[»]
3H5SX-ray2.00A/B2421-2989[»]
3H5UX-ray1.95A/B2421-2989[»]
3H98X-ray1.90A/B2421-2989[»]
3IGVX-ray2.60A/B2420-2989[»]
3MF5X-ray2.00A/B2421-2989[»]
3UA7X-ray1.50E/F2321-2331[»]
3UDLX-ray2.17A/B/C/D2420-2989[»]
3VQSX-ray1.90A/B/C/D2420-2989[»]
4A92X-ray2.73A/B1029-1657[»]
A/B1678-1690[»]
4B6EX-ray2.46A/B1029-1657[»]
4B6FX-ray2.89A/B1029-1657[»]
4B71X-ray2.50A/B1029-1657[»]
4B73X-ray2.50A/B1029-1657[»]
4B74X-ray2.18A/B1029-1657[»]
4B75X-ray2.53A/B1029-1655[»]
4B76X-ray2.14A/B1029-1657[»]
4DGVX-ray1.80A412-423[»]
4DGYX-ray1.80A412-423[»]
4EO6X-ray1.79A/B2422-2989[»]
4EO8X-ray1.80A/B2422-2989[»]
4IH5X-ray1.90A/B2421-2989[»]
4IH6X-ray2.20A/B2421-2989[»]
4IH7X-ray2.30A/B2421-2989[»]
4K8BX-ray2.80C/D1678-1689[»]
4KAIX-ray2.30A/B2420-2989[»]
4KB7X-ray1.85A/B2420-2989[»]
4KBIX-ray2.06A/B2420-2989[»]
4KE5X-ray2.11A/B2420-2989[»]
4MIAX-ray2.80A/B2421-2989[»]
4MIBX-ray2.30A/B2421-2989[»]
4MK7X-ray2.80A/B2421-2989[»]
4MK8X-ray2.09A/B2421-2989[»]
4MK9X-ray2.05A/B2421-2989[»]
4MKAX-ray2.05A/B2421-2989[»]
4MKBX-ray1.90A/B2421-2989[»]
8OHMX-ray2.30A1216-1650[»]
ProteinModelPortalP26663.
SMRP26663. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2420-2983.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP26663. 6 interactions.
MINTMINT-6548567.

Chemistry

BindingDBP26663.
ChEMBLCHEMBL6040.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

euHCVdbM58335.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
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. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEPS51693. HCV_NS2_PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP26663.

Entry information

Entry namePOLG_HCVBK
AccessionPrimary (citable) accession number: P26663
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 165 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references