ID   POLG_HCVE0              Reviewed;         138 AA.
AC   P27953;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   23-OCT-2007, entry version 48.
DE   Genome polyprotein [Contains: Envelope glycoprotein E1 (gp32) (gp35);
DE   Envelope glycoprotein E2 (NS1) (gp68) (gp70)] (Fragment).
OS   Hepatitis C virus (isolate EC10) (HCV).
OC   Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae;
OC   Hepacivirus.
OX   NCBI_TaxID=11106;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   MEDLINE=91112009; PubMed=1846505; DOI=10.1016/0042-6822(91)90104-J;
RA   Weiner A.J., Brauer M.J., Rosenblatt J., Richman K.H., Tung J.,
RA   Crawford K., Bonino F., Saracco G., Choo Q.-L., Houghton M., Han J.H.;
RT   "Variable and hypervariable domains are found in the regions of HCV
RT   corresponding to the flavivirus envelope and NS1 proteins and the
RT   pestivirus envelope glycoproteins.";
RL   Virology 180:842-848(1991).
RN   [2]
RP   REVIEW.
RX   PubMed=10718937; DOI=10.1046/j.1365-2893.2000.00201.x;
RA   McLauchlan J.;
RT   "Properties of the hepatitis C virus core protein: a structural
RT   protein that modulates cellular processes.";
RL   J. Viral Hepat. 7:2-14(2000).
RN   [3]
RP   REVIEW, AND SUBCELLULAR LOCATION.
RX   PubMed=14752815; DOI=10.1002/hep.20032;
RA   Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M.;
RT   "Structural biology of hepatitis C virus.";
RL   Hepatology 39:5-19(2004).
CC   -!- FUNCTION: E1 and E2 glycoproteins form a heterodimer that is
CC       involved in virus attachment to the host cell, virion
CC       internalization through clathrin-dependent endocytosis and fusion
CC       with host membrane. E1/E2 heterodimer binds to human LDLR, CD81
CC       and SCARB1/SR-BI receptors, but this binding is not sufficient for
CC       infection, some additional liver specific cofactors may be needed.
CC       The fusion function may possibly be carried by E1. E2 inhibits
CC       human EIF2AK2/PKR activation, preventing the establishment of an
CC       antiviral state. E2 is a viral ligand for CD209/DC-SIGN and
CC       CLEC4M/DC-SIGNR, which are respectively found on dendritic cells
CC       (DCs), and on liver sinusoidal endothelial cells and macrophage-
CC       like cells of lymph node sinuses. These interactions allow capture
CC       of circulating HCV particles by these cells and subsequent
CC       transmission to permissive cells. DCs act as sentinels in various
CC       tissues where they entrap pathogens and convey them to local
CC       lymphoid tissue or lymph node for establishment of immunity.
CC       Capture of circulating HCV particles by these SIGN+ cells may
CC       facilitate virus infection of proximal hepatocytes and lymphocyte
CC       subpopulations and may be essential for the establishment of
CC       persistent infection (By similarity).
CC   -!- SUBUNIT: E1 and E2 glycoproteins form a heterodimer that binds to
CC       human LDLR, CD81 and SCARB1 receptors. E2 binds and inhibits human
CC       EIF2AK2/PKR. Also binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR
CC       (By similarity).
CC   -!- SUBCELLULAR LOCATION: Envelope glycoprotein E1: Endoplasmic
CC       reticulum membrane; Single-pass type I membrane protein (By
CC       similarity). Note=The C-terminal transmembrane domain acts as a
CC       signal sequence and forms a hairpin structure before cleavage by
CC       host signal peptidase. After cleavage, the membrane sequence is
CC       retained at the C-terminus of the protein, serving as ER membrane
CC       anchor. A reorientation of the second hydrophobic stretch occurs
CC       after cleavage producing a single reoriented transmembrane domain.
CC       These events explain the final topology of the protein. ER
CC       retention of E1 is leaky and, in overexpression conditions, only a
CC       small fraction reaches the plasma membrane (By similarity).
CC   -!- SUBCELLULAR LOCATION: Envelope glycoprotein E2: Endoplasmic
CC       reticulum membrane; Single-pass type I membrane protein (By
CC       similarity). Note=The C-terminal transmembrane domain acts as a
CC       signal sequence and forms a hairpin structure before cleavage by
CC       host signal peptidase. After cleavage, the membrane sequence is
CC       retained at the C-terminus of the protein, serving as ER membrane
CC       anchor. A reorientation of the second hydrophobic stretch occurs
CC       after cleavage producing a single reoriented transmembrane domain.
CC       These events explain the final topology of the protein. ER
CC       retention of E2 is leaky and, in overexpression conditions, only a
CC       small fraction reaches the plasma membrane (By similarity).
CC   -!- DOMAIN: The transmembrane regions of envelope E1 and E2
CC       glycoproteins are involved in heterodimer formation, ER
CC       localization, and assembly of these proteins. Envelope E2
CC       glycoprotein contain two highly variable regions called
CC       hypervariable region 1 and 2 (HVR1 and HVR2) and two CD81-binding
CC       sites. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2
CC       and CD81-binding sites may be involved in sensitivity and/or
CC       resistance to IFN-alpha therapy (By similarity).
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       The structural proteins E1 and E2 are produced by proteolytic
CC       processing by the host signal peptidases.
CC   -!- PTM: Envelope E1 and E2 glycoproteins are highly N-glycosylated
CC       (By similarity).
CC   -!- MISCELLANEOUS: The virion of this virus is a nucleocapsid covered
CC       by a lipoprotein envelope. The envelope contains two proteins: the
CC       envelope glycoproteins E1 and E2.
CC   -!- SIMILARITY: Belongs to the hepaciviruses polyprotein family.
CC   -!- WEB RESOURCE: Name=euHCVdb; Note=The European HCV database;
CC       URL="http://euhcvdb.ibcp.fr";
CC   -!- WEB RESOURCE: Name=HCV databases;
CC       URL="http://hcv.lanl.gov/content/hcv-db/";
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DR   EMBL; X53136; CAA37296.1; -; Genomic_RNA.
DR   euHCVdb; X53136; -.
DR   InterPro; IPR002519; HCV_env.
DR   InterPro; IPR002531; HCV_NS1.
DR   Pfam; PF01539; HCV_env; 1.
DR   Pfam; PF01560; HCV_NS1; 1.
PE   3: Inferred from homology;
KW   Endoplasmic reticulum; Envelope protein; Fusion protein; Glycoprotein;
KW   Host-virus interaction; Membrane; Transmembrane; Virion.
FT   CHAIN        <1     84       Envelope glycoprotein E1 (Potential).
FT                                /FTId=PRO_0000037553.
FT   CHAIN        85   >138       Envelope glycoprotein E2 (Potential).
FT                                /FTId=PRO_0000037554.
FT   TOPO_DOM     <1     59       Lumenal (Potential).
FT   TRANSMEM     60     80       Potential.
FT   TOPO_DOM     81   >138       Lumenal (Potential).
FT   REGION       86    112       HVR1 (By similarity).
FT   SITE         84     85       Cleavage; by host signal peptidase
FT                                (Potential).
FT   CARBOHYD      6      6       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    118    118       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    124    124       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    131    131       N-linked (GlcNAc...) (Potential).
FT   NON_TER       1      1
FT   NON_TER     138    138
SQ   SEQUENCE   138 AA;  14781 MW;  CD3F0A962DEAB1AD CRC64;
     TTQGCNCSIY PGHITGHRMA WDMMMNWSPT TALVVAQLLR IPQAILDMIA GAHWGVLAGI
     AYFSMVGNWA KVLAVLLLFA GVDAETHVTG GIAAKTTASL TGLFNLGAKQ NIQLINTNGS
     WHINRTALNC NDSLNTGW
//