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P27958 (POLG_HCVH) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 163. 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·Alt products·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 1a (isolate H) (HCV) [Reference proteome]
Taxonomic identifier11108 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length3011 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.31

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.31

P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine By similarity. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity. Ref.31

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.31

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 By similarity. Cleaves and inhibits the host antiviral protein MAVS. Ref.31

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. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation. Ref.31

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.31

NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication. Ref.31

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. Activity is up-regulated by PKN2-mediated phosphorylation. Ref.38

Subunit structure

Core protein is a homomultimer that binds the C-terminal part of E1 and interacts with numerous cellular proteins. Interacts (via N-terminus finger domain) with human PKN2. 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). Interacts with human ACY3. 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.8 Ref.10 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.29 Ref.34 Ref.36 Ref.38 Ref.40

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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

Core protein p19: Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity Ref.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39.

Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein Potential. Host endoplasmic reticulum membrane; Single-pass type I membrane protein. 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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein Potential. Host endoplasmic reticulum membrane; Single-pass type I membrane protein. 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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39. Host cell membrane. 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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39.

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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39.

Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein. Host cytoplasmhost perinuclear region. Host mitochondrion. Note: Host membrane insertion occurs after processing by the NS3 protease. Ref.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

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.6 Ref.8 Ref.9 Ref.14 Ref.21 Ref.35 Ref.39

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.1 Ref.9

The N-terminus of NS5A acts as membrane anchor. The central part of NS5A seems to be intrinsically disordered and interacts with NS5B and host PKR. The C-terminus of NS5A contains a variable region called variable region 3 (V3) By similarity. Ref.1 Ref.9

The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases By similarity. Ref.1 Ref.9

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.1 Ref.9

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. Ref.5 Ref.26 Ref.28

Envelope E1 and E2 glycoproteins are highly N-glycosylated.

Core protein is phosphorylated by host PKC and PKA By similarity. Ref.7 Ref.38

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. Ref.7 Ref.38

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.

NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. Ref.30

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
   Coding sequence diversityRibosomal frameshifting
   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
Multifunctional enzyme
Reference proteome
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

proteolysis

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 10721731PubMed 20881089PubMed 11119590. Source: IntAct

ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

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

P266604EBI-6377335,EBI-6875462From a different organism.
Q99IB83EBI-8753518,EBI-6858513From a different organism.
ACTN1P128147EBI-6904388,EBI-351710From a different organism.
AP2M1Q96CW14EBI-6377335,EBI-297683From a different organism.
ARAP1Q96P483EBI-8753518,EBI-710003From a different organism.
ATF6BQ999415EBI-8763498,EBI-2841031From a different organism.
ATMQ133153EBI-6904388,EBI-495465From a different organism.
BIN1O004995EBI-8753518,EBI-719094From a different organism.
BIN1O00499-72EBI-8753518,EBI-8870146From a different organism.
C1QBPQ070214EBI-6377335,EBI-347528From a different organism.
CCDC86Q9H6F53EBI-8753518,EBI-721289From a different organism.
CD81P600337EBI-6904269,EBI-712921From a different organism.
CHEK2O960173EBI-6904388,EBI-1180783From a different organism.
CIDEBQ9UHD46EBI-6919131,EBI-7062247From a different organism.
CRABP1P297623EBI-8753518,EBI-725950From a different organism.
DDX5P178445EBI-6904388,EBI-351962From a different organism.
EIF2AK2P195254EBI-6904269,EBI-640775From a different organism.
Eif2ak3Q9Z2B55EBI-6904269,EBI-1226344From a different organism.
FGBP026754EBI-6377335,EBI-1034445From a different organism.
FYNP062414EBI-706378,EBI-515315From a different organism.
GRB2P629933EBI-706378,EBI-401755From a different organism.
HCKP086315EBI-706378,EBI-346340From a different organism.
IKBKEQ141642EBI-6919131,EBI-307369From a different organism.
LckP062403EBI-706378,EBI-1401From a different organism.
LTFP027883EBI-6904259,EBI-1058602From a different organism.
LYNP079485EBI-706378,EBI-79452From a different organism.
MAPKAPK3Q166445EBI-6377335,EBI-1384657From a different organism.
NCLP193384EBI-6904388,EBI-346967From a different organism.
PI4KAP423567EBI-8753518,EBI-723050From a different organism.
PMLP295906EBI-6377335,EBI-295890From a different organism.
PSMB8P280624EBI-3649474,EBI-372294From a different organism.
TBK1Q9UHD22EBI-6919131,EBI-356402From a different organism.
TMEM173Q86WV65EBI-8763498,EBI-2800345From a different organism.
VAPAQ9P0L05EBI-6904388,EBI-1059156From a different organism.

Alternative products

This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]

Note: The exact location of the ribosomal frameshift is unknown. The F protein seems to be generated by a -2 ribosomal frameshift located in the vicinity of codon 11 of the core protein coding sequence. However, some F proteins may also be generated by +1 ribosomal frameshift. Since the core gene encodes alternative reading frame proteins (ARFPs), many functions depicted for the core protein might belong to the ARFPs.
Isoform Genome polyprotein (identifier: P27958-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Produced by conventional translation.
Isoform F protein (identifier: P0C045-1)

Also known as: Frameshifted protein;

The sequence of this isoform can be found in the external entry P0C045.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by ribosomal frameshifting.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed; by host By similarity
Chain2 – 191190Core protein p21 Potential
PRO_0000037566
Chain2 – 177176Core protein p19 By similarity
PRO_0000037567
Propeptide178 – 19114ER anchor for the core protein, removed in mature form by host signal peptidase By similarity
PRO_0000037568
Chain192 – 383192Envelope glycoprotein E1 Potential
PRO_0000037569
Chain384 – 746363Envelope glycoprotein E2 Potential
PRO_0000037570
Chain747 – 80963p7
PRO_0000037571
Chain810 – 1026217Protease NS2-3 Potential
PRO_0000037572
Chain1027 – 1657631Serine protease NS3 Potential
PRO_0000037573
Chain1658 – 171154Non-structural protein 4A Potential
PRO_0000037574
Chain1712 – 1972261Non-structural protein 4B Potential
PRO_0000037575
Chain1973 – 2420448Non-structural protein 5A Potential
PRO_0000037576
Chain2421 – 3011591RNA-directed RNA polymerase Potential
PRO_0000037577

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 – 2990988Cytoplasmic Potential
Transmembrane2991 – 301121Helical; By similarity
Domain899 – 1026128Peptidase C18
Domain1217 – 1369153Helicase ATP-binding
Domain2634 – 2752119RdRp catalytic
Nucleotide binding1230 – 12378ATP 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
Region475 – 4817HVR2 By similarity
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
Region2249 – 230658NS4B-binding Potential
Region2351 – 242070Basal 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 bias2286 – 232742Pro-rich
Compositional bias2996 – 29994Poly-Leu

Sites

Active site9521For protease NS2-3 activity; shared with dimeric partner
Active site9721For protease NS2-3 activity; shared with dimeric partner
Active site9931For protease NS2-3 activity; shared with dimeric partner
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
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
Site809 – 8102Cleavage; by host signal peptidase
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
Site2420 – 24212Cleavage; 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 By similarity
Modified residue21971Phosphoserine; by host; in p58 By similarity
Modified residue22011Phosphoserine; by host; in p58 By similarity
Modified residue22041Phosphoserine; by host; in p58 By similarity
Modified residue23211Phosphoserine; by host Ref.7
Lipidation19681S-palmitoyl cysteine; by host Ref.30
Lipidation19721S-palmitoyl cysteine; by host; partial Ref.30
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
Glycosylation4761N-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

Natural variations

Natural variant2121V → I in strain: Isolate H77.
Natural variant2971H → R in strain: Isolate H77.
Natural variant3031D → S in strain: Isolate H77.
Natural variant3211N → D in strain: Isolate H77.
Natural variant3601K → A in strain: Isolate H77.
Natural variant3911N → S in strain: Isolate H77.
Natural variant3941R → H in strain: Isolate H77.
Natural variant4311E → D in strain: Isolate H77.
Natural variant4341N → T in strain: Isolate H77.
Natural variant4441Q → R in strain: Isolate H77.
Natural variant4571A → T in strain: Isolate H77.
Natural variant564 – 5663CGA → RGV in strain: Isolate H77.
Natural variant5891Y → H in strain: Isolate H77.
Natural variant6021R → W in strain: Isolate H77.
Natural variant6501E → G in strain: Isolate H77.
Natural variant7731C → R in strain: Isolate H77.
Natural variant7871V → A in strain: Isolate H77.
Natural variant7901L → F in strain: Isolate H77.
Natural variant8771T → M in strain: Isolate H77.
Natural variant8831A → T in strain: Isolate H77.
Natural variant9481C → Y in strain: Isolate H77.
Natural variant9541A → T in strain: Isolate H77.
Natural variant10261L → Q in strain: Isolate H77.
Natural variant10331A → T in strain: Isolate H77.
Natural variant10491G → S in strain: Isolate H77.
Natural variant11001T → M in strain: Isolate H77.
Natural variant11211T → A in strain: Isolate H77.
Natural variant11731T → A in strain: Isolate H77.
Natural variant12021E → G in strain: Isolate H77.
Natural variant12141S → P in strain: Isolate H77.
Natural variant12471K → Q in strain: Isolate H77.
Natural variant13031A → G in strain: Isolate H77.
Natural variant13271S → L in strain: Isolate H77.
Natural variant15561G → E in strain: Isolate H77.
Natural variant16081R → W in strain: Isolate H77.
Natural variant17421H → Q in strain: Isolate H77.
Natural variant1839 – 18402LD → IG in strain: Isolate H77.
Natural variant18931A → V in strain: Isolate H77.
Natural variant1898 – 19003FAS → CAA in strain: Isolate H77.
Natural variant19051R → H in strain: Isolate H77.
Natural variant19401A → V in strain: Isolate H77.
Natural variant20431T → A in strain: Isolate H77.
Natural variant20531K → R in strain: Isolate H77.
Natural variant20611F → L in strain: Isolate H77.
Natural variant21021V → I in strain: Isolate H77.
Natural variant21851A → E in strain: Isolate H77.
Natural variant22831P → R in strain: Isolate H77.
Natural variant22961L → P in strain: Isolate H77.
Natural variant23411P → S in strain: Isolate H77.
Natural variant23551S → P in strain: Isolate H77.
Natural variant24001L → F in strain: Isolate H77.
Natural variant24251S → T in strain: Isolate H77.
Natural variant24691K → Q in strain: Isolate H77.
Natural variant25121A → T in strain: Isolate H77.
Natural variant26371L → F in strain: Isolate H77.
Natural variant27031R → G in strain: Isolate H77.
Natural variant27151R → C in strain: Isolate H77.
Natural variant27551S → N in strain: Isolate H77.
Natural variant29251W → R in strain: Isolate H77.
Natural variant29331A → S in strain: Isolate H77.
Natural variant29371K → R in strain: Isolate H77.
Natural variant29601T → A in strain: Isolate H77.

Experimental info

Mutagenesis7201V → L: Increases processing between E2 and p7. Ref.28
Mutagenesis7791K → I: Virus can no longer infect chimpanzee. Ref.19
Mutagenesis7811R → S: Virus can no longer infect chimpanzee. Ref.19
Mutagenesis9521H → A: Complete loss of NS2-NS3 cleavage. Ref.4 Ref.46
Mutagenesis9931C → A: Complete loss of NS2-NS3 cleavage. Ref.4 Ref.46
Mutagenesis11651S → A: Complete loss of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B cleavages. Ref.4
Mutagenesis19681C → A: Strong decrease in NS4B palmitoylation. Ref.30
Mutagenesis19721C → A: Slight decrease in NS4B palmitoylation. Ref.30
Mutagenesis23211S → A: Loss of phosphorylation. Ref.7

Secondary structure

.................................................................................................................................................................................................................................................................................................... 3011
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Genome polyprotein [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 772CBB29CCD94753

FASTA3,011327,146
        10         20         30         40         50         60 
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG 

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

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

       190        200        210        220        230        240 
LLSCLTVPAS AYQVRNSSGL YHVTNDCPNS SVVYEAADAI LHTPGCVPCV REGNASRCWV 

       250        260        270        280        290        300 
AVTPTVATRD GKLPTTQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRHHWT 

       310        320        330        340        350        360 
TQDCNCSIYP GHITGHRMAW NMMMNWSPTA ALVVAQLLRI PQAIMDMIAG AHWGVLAGIK 

       370        380        390        400        410        420 
YFSMVGNWAK VLVVLLLFAG VDAETHVTGG NAGRTTAGLV GLLTPGAKQN IQLINTNGSW 

       430        440        450        460        470        480 
HINSTALNCN ESLNTGWLAG LFYQHKFNSS GCPERLASCR RLTDFAQGWG PISYANGSGL 

       490        500        510        520        530        540 
DERPYCWHYP PRPCGIVPAK SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ANDTDVFVLN 

       550        560        570        580        590        600 
NTRPPLGNWF GCTWMNSTGF TKVCGAPPCV IGGVGNNTLL CPTDCFRKYP EATYSRCGSG 

       610        620        630        640        650        660 
PRITPRCMVD YPYRLWHYPC TINYTIFKVR MYVGGVEHRL EAACNWTRGE RCDLEDRDRS 

       670        680        690        700        710        720 
ELSPLLLSTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGVGSSIA SWAIKWEYVV 

       730        740        750        760        770        780 
LLFLLLADAR VCSCLWMMLL ISQAEAALEN LVILNAASLA GTHGLVSFLV FFCFAWYLKG 

       790        800        810        820        830        840 
RWVPGAVYAL YGMWPLLLLL LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS 

       850        860        870        880        890        900 
WCMWWLQYFL TRVEAQLHVW VPPLNVRGGR DAVILLTCVV HPALVFDITK LLLAIFGPLW 

       910        920        930        940        950        960 
ILQASLLKVP YFVRVQGLLR ICALARKIAG GHYVQMAIIK LGALTGTCVY NHLAPLRDWA 

       970        980        990       1000       1010       1020 
HNGLRDLAVA VEPVVFSRME TKLITWGADT AACGDIINGL PVSARRGQEI LLGPADGMVS 

      1030       1040       1050       1060       1070       1080 
KGWRLLAPIT AYAQQTRGLL GCIITSLTGR DKNQVEGEVQ IVSTATQTFL ATCINGVCWT 

      1090       1100       1110       1120       1130       1140 
VYHGAGTRTI ASPKGPVIQT YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI 

      1150       1160       1170       1180       1190       1200 
PVRRRGDSRG SLLSPRPISY LKGSSGGPLL CPTGHAVGLF RAAVCTRGVA KAVDFIPVEN 

      1210       1220       1230       1240       1250       1260 
LETTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAKGYK VLVLNPSVAA 

      1270       1280       1290       1300       1310       1320 
TLGFGAYMSK AHGVDPNIRT GVRTITTGSP ITYSTYGKFL ADAGCSGGAY DIIICDECHS 

      1330       1340       1350       1360       1370       1380 
TDATSISGIG TVLDQAETAG ARLVVLATAT PPGSVTVSHP NIEEVALSTT GEIPFYGKAI 

      1390       1400       1410       1420       1430       1440 
PLEVIKGGRH LIFCHSKKKC DELAAKLVAL GINAVAYYRG LDVSVIPTSG DVVVVSTDAL 

      1450       1460       1470       1480       1490       1500 
MTGFTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRTQRRGR TGRGKPGIYR 

      1510       1520       1530       1540       1550       1560 
FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV CQDHLGFWEG 

      1570       1580       1590       1600       1610       1620 
VFTGLTHIDA HFLSQTKQSG ENFPYLVAYQ ATVCARAQAP PPSWDQMRKC LIRLKPTLHG 

      1630       1640       1650       1660       1670       1680 
PTPLLYRLGA VQNEVTLTHP ITKYIMTCMS ADLEVVTSTW VLVGGVLAAL AAYCLSTGCV 

      1690       1700       1710       1720       1730       1740 
VIVGRIVLSG KPAIIPDREV LYQEFDEMEE CSQHLPYIEQ GMMLAEQFKQ KALGLLQTAS 

      1750       1760       1770       1780       1790       1800 
RHAEVITPAV QTNWQKLEVF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTAAVTSP 

      1810       1820       1830       1840       1850       1860 
LTTGQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAALD SVGLGKVLVD ILAGYGAGVA 

      1870       1880       1890       1900       1910       1920 
GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALAVGVVFAS ILRRRVGPGE GAVQWMNRLI 

      1930       1940       1950       1960       1970       1980 
AFASRGNHVS PTHYVPESDA AARVTAILSS LTVTQLLRRL HQWISSECTT PCSGSWLRDI 

      1990       2000       2010       2020       2030       2040 
WDWICEVLSD FKTWLKAKLM PQLPGIPFVS CQRGYRGVWR GDGIMHTRCH CGAEITGHVK 

      2050       2060       2070       2080       2090       2100 
NGTMRIVGPR TCKNMWSGTF FINAYTTGPC TPLPAPNYKF ALWRVSAEEY VEIRRVGDFH 

      2110       2120       2130       2140       2150       2160 
YVSGMTTDNL KCPCQIPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG LHEYPVGSQL 

      2170       2180       2190       2200       2210       2220 
PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSMAS SSASQLSAPS LKATCTANHD 

      2230       2240       2250       2260       2270       2280 
SPDAELIEAN LLWRQEMGGN ITRVESENKV VILDSFDPLV AEEDEREVSV PAEILRKSRR 

      2290       2300       2310       2320       2330       2340 
FAPALPVWAR PDYNPLLVET WKKPDYEPPV VHGCPLPPPR SPPVPPPRKK RTVVLTESTL 

      2350       2360       2370       2380       2390       2400 
PTALAELATK SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DVESYSSMPP LEGEPGDPDL 

      2410       2420       2430       2440       2450       2460 
SDGSWSTVSS GADTEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL LRHHNLVYST 

      2470       2480       2490       2500       2510       2520 
TSRSACQRKK KVTFDRLQVL DSHYQDVLKE VKAAASKVKA NLLSVEEACS LAPPHSAKSK 

      2530       2540       2550       2560       2570       2580 
FGYGAKDVRC HARKAVAHIN SVWKDLLEDS VTPIDTTIMA KNEVFCVQPE KGGRKPARLI 

      2590       2600       2610       2620       2630       2640 
VFPDLGVRVC EKMALYDVVS KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGLSYD 

      2650       2660       2670       2680       2690       2700 
TRCFDSTVTE SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR 

      2710       2720       2730       2740       2750       2760 
ASRVLTTSCG NTLTRYIKAR AACRAAGLQD CTMLVCGDDL VVICESAGVQ EDAASLRAFT 

      2770       2780       2790       2800       2810       2820 
EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR VYYLTRDPTT PLARAAWETA 

      2830       2840       2850       2860       2870       2880 
RHTPVNSWLG NIIMFAPTLW ARMILMTHFF SVLIARDQLE QALNCEIYGA CYSIEPLDLP 

      2890       2900       2910       2920       2930       2940 
PIIQRLHGLS AFSLHSYSPG EINRVAACLR KLGVPPLRAW RHRAWSVRAR LLARGGKAAI 

      2950       2960       2970       2980       2990       3000 
CGKYLFNWAV RTKLKLTPIT AAGRLDLSGW FTAGYSGGDI YHSVSHARPR WFWFCLLLLA 

      3010 
AGVGIYLLPN R 

« Hide

Isoform F protein (Frameshifted protein) [UniParc].

See P0C045.

References

[1]"Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates."
Inchauspe G., Zebedee S., Lee D.H.H., Sugitani M., Nasoff M., Prince A.M.
Proc. Natl. Acad. Sci. U.S.A. 88:10292-10296(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], DOMAIN V3 REGION.
[2]"Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA."
Kolykhalov A.A., Agapov E.V., Blight K.J., Mihalik K., Feinstone S.M., Rice C.M.
Science 277:570-574(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate H77.
[3]"Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee."
Yanagi M., Purcell R.H., Emerson S.U., Bukh J.
Proc. Natl. Acad. Sci. U.S.A. 94:8738-8743(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate H77.
[4]"A second hepatitis C virus-encoded proteinase."
Grakoui A., McCourt D.W., Wychowski C., Feinstone S.M., Rice C.M.
Proc. Natl. Acad. Sci. U.S.A. 90:10583-10587(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF THE CYSTEINE PROTEASE, MUTAGENESIS OF HIS-952; CYS-993 AND SER-1165.
[5]"Expression and identification of hepatitis C virus polyprotein cleavage products."
Grakoui A., Wychowski C., Lin C., Feinstone S.M., Rice C.M.
J. Virol. 67:1385-1395(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[6]"Characterization of the nuclear localization signal and subcellular distribution of hepatitis C virus nonstructural protein NS5A."
Ide Y., Zhang L., Chen M., Inchauspe G., Bahl C., Sasaguri Y., Padmanabhan R.
Gene 182:203-211(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF NS5A, NUCLEAR LOCALIZATION SIGNAL.
[7]"Identification of the major phosphorylation site of the hepatitis C virus H strain NS5A protein as serine 2321."
Reed K.E., Rice C.M.
J. Biol. Chem. 274:28011-28018(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-2321, MUTAGENESIS OF SER-2321.
[8]"Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP."
Ghosh A.K., Majumder M., Steele R., Yaciuk P., Chrivia J., Ray R., Ray R.B.
J. Biol. Chem. 275:7184-7188(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH SRCAP, SUBCELLULAR LOCATION OF NS5A.
[9]"Charged residues in the transmembrane domains of hepatitis C virus glycoproteins play a major role in the processing, subcellular localization, and assembly of these envelope proteins."
Cocquerel L., Wychowski C., Minner F., Penin F., Dubuisson J.
J. Virol. 74:3623-3633(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF E1 AND E2, ROLE OF TRANSMEMBRANE DOMAINS.
[10]"Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation."
Kittlesen D.J., Chianese-Bullock K.A., Yao Z.Q., Braciale T.J., Hahn Y.S.
J. Clin. Invest. 106:1239-1249(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF CORE PROTEIN WITH HUMAN C1QR1.
[11]"Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment."
Penin F., Combet C., Germanidis G., Frainais P.-O., Deleage G., Pawlotsky J.-M.
J. Virol. 75:5703-5710(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF HVR1 REGION.
[12]"Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase."
Schmidt-Mende J., Bieck E., Huegle T., Penin F., Rice C.M., Blum H.E., Moradpour D.
J. Biol. Chem. 276:44052-44063(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY OF NS5B.
[13]"Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins."
Cocquerel L., Op de Beeck A., Lambot M., Roussel J., Delgrange D., Pillez A., Wychowski C., Penin F., Dubuisson J.
EMBO J. 21:2893-2902(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY OF ENVELOPE GLYCOPROTEINS E1 AND E2.
[14]"Subcellular localization and topology of the p7 polypeptide of hepatitis C virus."
Carrere-Kremer S., Montpellier-Pala C., Cocquerel L., Wychowski C., Penin F., Dubuisson J.
J. Virol. 76:3720-3730(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, SUBCELLULAR LOCATION OF P7.
[15]"An amino-terminal amphipathic alpha-helix mediates membrane association of the hepatitis C virus nonstructural protein 5A."
Brass V., Bieck E., Montserret R., Woelk B., Hellings J.A., Blum H.E., Penin F., Moradpour D.
J. Biol. Chem. 277:8130-8139(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY OF NS5A.
[16]"Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex."
Egger D., Woelk B., Gosert R., Bianchi L., Blum H.E., Moradpour D., Bienz K.
J. Virol. 76:5974-5984(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REPLICATION COMPLEX.
[17]"Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons."
Gosert R., Egger D., Lohmann V., Bartenschlager R., Blum H.E., Bienz K., Moradpour D.
J. Virol. 77:5487-5492(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REPLICATION COMPLEX.
[18]"The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives."
Pavlovic D., Neville D.C., Argaud O., Blumberg B., Dwek R.A., Fischer W.B., Zitzmann N.
Proc. Natl. Acad. Sci. U.S.A. 100:6104-6108(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION OF P7 BY LONG-ALKYL-CHAIN IMINOSUGAR DERIVATIVES.
[19]"The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences."
Sakai A., Claire M.S., Faulk K., Govindarajan S., Emerson S.U., Purcell R.H., Bukh J.
Proc. Natl. Acad. Sci. U.S.A. 100:11646-11651(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-779 AND ARG-781.
Strain: Isolate H77.
[20]"Protein-protein interactions between hepatitis C virus nonstructural proteins."
Dimitrova M., Imbert I., Kieny M.P., Schuster C.
J. Virol. 77:5401-5414(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION BETWEEN NON-STRUCTURAL PROTEINS.
[21]"Topology of the membrane-associated hepatitis C virus protein NS4B."
Lundin M., Monne M., Widell A., Von Heijne G., Persson M.A.A.
J. Virol. 77:5428-5438(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, SUBCELLULAR LOCATION OF NS4B.
Strain: Isolate H77.
[22]"CD81-dependent binding of hepatitis C virus E1E2 heterodimers."
Cocquerel L., Kuo C.-C., Dubuisson J., Levy S.
J. Virol. 77:10677-10683(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81.
[23]"Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes."
Bartosch B., Dubuisson J., Cosset F.-L.
J. Exp. Med. 197:633-642(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81; LDLR AND SCARB1.
[24]"Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor."
Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F.-L.
J. Biol. Chem. 278:41624-41630(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF E1/E2 HETERODIMER WITH HUMAN CD81.
[25]"Characterization of functional hepatitis C virus envelope glycoproteins."
Op De Beeck A., Voisset C., Bartosch B., Ciczora Y., Cocquerel L., Keck Z., Foung S., Cosset F.-L., Dubuisson J.
J. Virol. 78:2994-3002(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF E1 AND E2.
[26]"Regulation of hepatitis C virus polyprotein processing by signal peptidase involves structural determinants at the p7 sequence junctions."
Carrere-Kremer S., Montpellier C., Lorenzo L., Brulin B., Cocquerel L., Belouzard S., Penin F., Dubuisson J.
J. Biol. Chem. 279:41384-41392(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[27]"L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus."
Cormier E.G., Durso R.J., Tsamis F., Boussemart L., Manix C., Olson W.C., Gardner J.P., Dragic T.
Proc. Natl. Acad. Sci. U.S.A. 101:14067-14072(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CD209/DC-SIGN AND CLEC4M/DC-SIGNR.
Strain: Isolate H77.
[28]"Analysis of the processing and transmembrane topology of the E2p7 protein of hepatitis C virus."
Isherwood B.J., Patel A.H.
J. Gen. Virol. 86:667-676(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE BETWEEN E2 AND P7, TOPOLOGY OF P7, MUTAGENESIS OF VAL-720.
[29]"Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity."
Li X.D., Sun L., Seth R.B., Pineda G., Chen Z.J.
Proc. Natl. Acad. Sci. U.S.A. 102:17717-17722(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS3 PROTEASE WITH HUMAN MAVS.
[30]"Palmitoylation and polymerization or in protein-protein interactions of hepatitis C virus NS4B protein."
Yu G.-Y., Lee K.-J., Gao L., Lai M.M.C.
J. Virol. 80:6013-6023(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-1968 AND CYS-1972 (NS4B) BY HOST, MUTAGENESIS OF CYS-1968 AND CYS-1972.
Strain: Isolate H77.
[31]"Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis."
Codran A., Royer C., Jaeck D., Bastien-Valle M., Baumert T.F., Kieny M.P., Pereira C.A., Martin J.P.
J. Gen. Virol. 87:2583-2593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF E1 AND E2.
Strain: Isolate H77.
[32]"The membrane-active regions of the hepatitis C virus E1 and E2 envelope glycoproteins."
Perez-Berna A.J., Moreno M.R., Guillen J., Bernabeu A., Villalain J.
Biochemistry 45:3755-3768(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF THE FUSION PEPTIDE.
Strain: Isolate H77.
[33]"Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein."
Lundin M., Lindstrom H., Groenwall C., Persson M.A.
J. Gen. Virol. 87:3263-3272(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY OF NS4B.
Strain: Isolate H77.
[34]"Molecular and structural characterization of the domain 2 of hepatitis C virus non-structural protein 5A."
Liang Y., Kang C.B., Yoon H.S.
Mol. Cells 22:13-20(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF NS5A WITH NS5B AND HOST PKR.
[35]"Conserved determinants for membrane association of nonstructural protein 5A from hepatitis C virus and related viruses."
Brass V., Pal Z., Sapay N., Deleage G., Blum H.E., Penin F., Moradpour D.
J. Virol. 81:2745-2757(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF NS5A.
[36]"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.
[37]"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.
[38]"Protein kinase C-related kinase 2 regulates hepatitis C virus RNA polymerase function by phosphorylation."
Kim S.J., Kim J.H., Kim Y.G., Lim H.S., Oh J.W.
J. Biol. Chem. 279:50031-50041(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION, INTERACTION WITH PKN2.
[39]"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.
[40]"Identification of a novel protein binding to hepatitis C virus core protein."
Chen Y.R., Chen T.Y., Zhang S.L., Lin S.M., Zhao Y.R., Ye F., Zhang X., Shi L., Dang S.S., Liu M.
J. Gastroenterol. Hepatol. 24:1300-1304(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ACY3.
[41]"Structure of the hepatitis C virus RNA helicase domain."
Yao N., Hesson T., Cable M.B., Hong Z., Kwong A.D., Le H.V., Weber P.C.
Nat. Struct. Biol. 4:463-467(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1206-1656.
[42]"Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide."
Kim J.L., Morgenstern K.A., Lin C., Fox T., Dwyer M.D., Landro J.A., Chambers S.P., Markland W., Lepre C.A., O'Malley E.T., Harbeson S.L., Rice C.M., Murcko M.A., Caron P.R., Thomson J.A.
Cell 87:343-355(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1027-1206 IN COMPLEX WITH NS4A.
[43]"Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding."
Kim J.L., Morgenstern K.A., Griffith J.P., Dwyer M.D., Thomson J.A., Murcko M.A., Lin C., Caron P.R.
Structure 6:89-100(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1192-1657.
[44]"Solution structure and backbone dynamics of an engineered arginine-rich subdomain 2 of the hepatitis C virus NS3 RNA helicase."
Liu D., Wang Y.-S., Gesell J.J., Wyss D.F.
J. Mol. Biol. 314:543-561(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1353-1507.
[45]"Pyrrolidine-5,5-trans-lactams. 2. The use of X-ray crystal structure data in the optimization of P3 and P4 substituents."
Andrews D.M., Chaignot H., Coomber B.A., Good A.C., Hind S.L., Johnson M.R., Jones P.S., Mills G., Robinson J.E., Skarzynski T., Slater M.J., Somers D.O.
Org. Lett. 4:4479-4482(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1027-1207.
[46]"Structure of the catalytic domain of the hepatitis C virus NS2-3 protease."
Lorenz I.C., Marcotrigiano J., Dentzer T.G., Rice C.M.
Nature 442:831-835(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 903-1026, MUTAGENESIS OF HIS-952 AND CYS-993.
+Additional computationally mapped references.

Web resources

euHCVdb

The European HCV database

Virus Pathogen Resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M67463 Genomic RNA. Translation: AAA45534.1.
AF009606 Genomic RNA. Translation: AAB66324.1.
AF011751 Genomic RNA. Translation: AAB67036.1.
AF011752 Genomic RNA. Translation: AAB67037.1.
AF011753 Genomic RNA. Translation: AAB67038.1.
PIRGNWVCH. A36814.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A1RX-ray2.50A/B1027-1206[»]
1A1VX-ray2.20A1193-1657[»]
1CWXNMR-A2-45[»]
1HEIX-ray2.10A/B1206-1656[»]
1JR6NMR-A1353-1507[»]
1N1LX-ray2.60A/B1027-1206[»]
1ONBNMR-A1353-1507[»]
1R7CNMR-A1973-2003[»]
1R7DNMR-A1973-2003[»]
1R7ENMR-A1973-2003[»]
1R7FNMR-A1973-2003[»]
1R7GNMR-A1973-2003[»]
1RGQX-ray2.90A/B1027-1206[»]
2A4RX-ray2.40A/C1027-1207[»]
B/D1680-1696[»]
2F9VX-ray2.60A/C1027-1207[»]
B/D1680-1696[»]
2HD0X-ray2.28A/B/C/D/E/F/G/H/I/J/K/L903-1026[»]
2JXFNMR-A1751-1780[»]
2KDRNMR-X1938-1965[»]
2O8MX-ray2.00C/D1678-1695[»]
2OBOX-ray2.60A/C1022-1207[»]
B/D1677-1695[»]
2OBQX-ray2.50B/D1678-1695[»]
2OC0X-ray2.30A/C1022-1207[»]
B/D1677-1695[»]
2OC1X-ray2.70A/C1022-1207[»]
B/D1677-1695[»]
2OC7X-ray2.70A/C1022-1207[»]
B/D1677-1695[»]
2OC8X-ray2.66A/C1022-1207[»]
B/D1677-1695[»]
2OINX-ray2.50A/B1027-1207[»]
2P59X-ray2.90A/B1027-1207[»]
C/D1678-1696[»]
2XI2X-ray1.80A/B/C2421-2990[»]
2XI3X-ray1.70A/B2421-2990[»]
2XNIX-ray3.30A/B1027-1206[»]
4JZNX-ray2.05K434-446[»]
4JZOX-ray2.22I/J/K/L434-446[»]
4MWFX-ray2.64C/D412-459[»]
C/D486-645[»]
DisProtDP00588.
ProteinModelPortalP27958.
SMRP27958. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP27958. 194 interactions.
MINTMINT-106294.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

euHCVdbAF009606.
AF011751.
AF011752.
AF011753.
M67463.

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

EvolutionaryTraceP27958.

Entry information

Entry namePOLG_HCVH
AccessionPrimary (citable) accession number: P27958
Secondary accession number(s): O36579 expand/collapse secondary AC list , O36608, O36609, O36610
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 163 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