P27953 (POLG_HCVE0) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 71. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Hepatitis C virus (isolate EC10) (HCV)|
|Taxonomic identifier||11106 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Hepacivirus ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||138 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Inferred from homology|
General annotation (Comments)
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.
E1 and E2 glycoproteins form a heterodimer that binds to human LDLR, CD81 and SCARB1 receptors. E2 binds and inhibits human EIF2AK2/PKR. Also binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR By similarity.
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 By similarity. Ref.3
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 By similarity. Ref.3
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) and two CD81-binding sites. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2 and CD81-binding sites may be involved in sensitivity and/or resistance to IFN-alpha therapy By similarity.
Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins E1 and E2 are produced by proteolytic processing by the host signal peptidases.
Envelope E1 and E2 glycoproteins are highly N-glycosylated By similarity.
The virion of this virus is a nucleocapsid covered by a lipoprotein envelope. The envelope contains two proteins: the envelope glycoproteins E1 and E2.
Belongs to the hepacivirus polyprotein family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||‹1 – 84||›84||Envelope glycoprotein E1 Potential||PRO_0000037553|
|Chain||85 – ›138||›54||Envelope glycoprotein E2 Potential||PRO_0000037554|
|Topological domain||‹1 – 59||›59||Lumenal Potential|
|Transmembrane||60 – 80||21||Helical; Potential|
|Topological domain||81 – ›138||›58||Lumenal Potential|
|Region||86 – 112||27||HVR1 By similarity|
|Site||84 – 85||2||Cleavage; by host signal peptidase Potential|
Amino acid modifications
|Glycosylation||6||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||118||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||124||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||131||1||N-linked (GlcNAc...); by host Potential|
|||"Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins."|
Weiner A.J., Brauer M.J., Rosenblatt J., Richman K.H., Tung J., Crawford K., Bonino F., Saracco G., Choo Q.-L., Houghton M., Han J.H.
Virology 180:842-848(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes."|
J. Viral Hepat. 7:2-14(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"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.
|X53136 Genomic RNA. Translation: CAA37296.1.|
3D structure databases
Protocols and materials databases
Family and domain databases
|InterPro||IPR002519. HCV_env. |
|Pfam||PF01539. HCV_env. 1 hit. |
PF01560. HCV_NS1. 1 hit.
|ProDom||PD001388. HCV_env. 1 hit. |
[Graphical view] [Entries sharing at least one domain]
|Accession||Primary (citable) accession number: P27953|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|