Reviewed, UniProtKB/Swiss-Prot P27953 (POLG_HCVE0)

Names and origin

Protein names	Recommended name:     Genome polyprotein Cleaved into the following 2 chains:     1- Recommended name:             Envelope glycoprotein E1         Alternative name(s):             gp32             gp35     2- Recommended name:             Envelope glycoprotein E2         Alternative name(s):             NS1             gp68             gp70
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]

Protein attributes

Sequence length	138 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	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. 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.
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) 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.
Post-translational modification	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.
Miscellaneous	The virion of this virus is a nucleocapsid covered by a lipoprotein envelope. The envelope contains two proteins: the envelope glycoproteins E1 and E2.
Sequence similarities	Belongs to the hepaciviruses polyprotein family.

Ontologies

Keywords
Biological process	Fusion protein Host-virus interaction
Cellular component	Endoplasmic reticulum Envelope protein Membrane Virion
Domain	Transmembrane
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – 84	›84	Envelope glycoprotein E1 Potential		PRO_0000037553
	Chain	85 – ›138	›54	Envelope glycoprotein E2 Potential		PRO_0000037554
Regions
	Topological domain	‹1 – 59	›59	Lumenal Potential
	Transmembrane	60 – 80	21	Potential
	Topological domain	81 – ›138	›58	Lumenal Potential
	Region	86 – 112	27	HVR1 By similarity
Sites
	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
Experimental info
	Non-terminal residue	1	1
	Non-terminal residue	138	1

Sequences

	Sequence		Length	Mass (Da)
	P27953-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: CD3F0A962DEAB1AD	FASTA	138	14,781
	10 20 30 40 50 60 TTQGCNCSIY PGHITGHRMA WDMMMNWSPT TALVVAQLLR IPQAILDMIA GAHWGVLAGI 70 80 90 100 110 120 AYFSMVGNWA KVLAVLLLFA GVDAETHVTG GIAAKTTASL TGLFNLGAKQ NIQLINTNGS 130 WHINRTALNC NDSLNTGW

References

[1]	"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: 1846505] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"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: 10718937] [Abstract] Cited for: REVIEW.
[3]	"Structural biology of hepatitis C virus." Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M. Hepatology 39:5-19(2004) [PubMed: 14752815] [Abstract] Cited for: REVIEW, SUBCELLULAR LOCATION.

Web resources

euHCVdb

The European HCV database

HCV database

Cross-references

Sequence databases
EMBLGenBankDDBJ	X53136 Genomic RNA. Translation: CAA37296.1.
3D structure databases
ModBase	Search...
Organism-specific databases
euHCVdb	X53136.
Family and domain databases
InterPro	IPR002519. HCV_env. IPR002531. HCV_NS1. [Graphical view]
Pfam	PF01539. HCV_env. 1 hit. PF01560. HCV_NS1. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_HCVE0

Accession

Primary (citable) accession number: P27953

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)