Q67875 (HBSAG_HBVD6) Reviewed, UniProtKB/Swiss-Prot
Last modified December 11, 2013. Version 56. History...
Names and origin
|Protein names||Recommended name:|
Large envelope protein
Large S protein
Large surface protein
Major surface antigen
|Organism||Hepatitis B virus genotype D subtype ayw (isolate Italy/CI/1992) (HBV-D) [Complete proteome]|
|Taxonomic identifier||489489 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
Pan troglodytes (Chimpanzee) [TaxID: 9598]
|Sequence length||389 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assumes fusion between virion membrane and endosomal membrane Probable. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein By similarity.
The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid By similarity.
Li-HBsAg interacts with capsid protein and with HDV Large delta antigen. Isoform M associates with host chaperone CANX through its pre-S2 N glycan. This association may be essential for M proper secretion By similarity.
Virion membrane By similarity.
The large envelope protein is synthesized with the pre-S region at the cytosolic side of the endoplasmic reticulum and, hence will be within the virion after budding. Therefore the pre-S region is not N-glycosylated. Later a post-translational translocation of N-terminal pre-S and TM1 domains occur in about 50% of proteins at the virion surface. These molecules change their topology by an unknown mechanism, resulting in exposure of pre-S region at virion surface.
Myristoylated By similarity.
Systematic vaccination of individuals at risk of exposure to the virus has been the main method of controlling the morbidity and mortality associated with hepatitis B. The first hepatitis B vaccine was manufactured by the purification and inactivation of HBsAg obtained from the plasma of chronic hepatitis B virus carriers. The vaccine is now produced by recombinant DNA techniques and expression of the S isoform in yeast cells. The pre-S region do not seem to induce strong enough antigenic response.
Belongs to the orthohepadnavirus major surface antigen family.
|This entry describes 2 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]|
|Isoform L (identifier: Q67875-1) |
Also known as: Large envelope protein; LHB; L-HBsAg;
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.
|Isoform S (identifier: Q67875-2) |
Also known as: Small envelope protein; SHB; S-HBsAg;
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed; by host By similarity|
|Chain||2 – 389||388||Large envelope protein||PRO_0000319087|
|Topological domain||2 – 242||241||Intravirion; in internal conformation Potential|
|Topological domain||2 – 170||169||Virion surface; in external conformation Potential|
|Transmembrane||171 – 191||21||Helical; Note=In external conformation; Potential|
|Topological domain||192 – 242||51||Intravirion; in external conformation Potential|
|Transmembrane||243 – 263||21||Helical; Potential|
|Topological domain||264 – 337||74||Virion surface Potential|
|Transmembrane||338 – 358||21||Helical; Potential|
|Topological domain||359 – 364||6||Intravirion Potential|
|Transmembrane||365 – 387||23||Helical; Potential|
|Topological domain||388 – 389||2||Virion surface Potential|
|Region||2 – 163||162||Pre-S|
|Region||2 – 108||107||Pre-S1|
|Region||109 – 163||55||Pre-S2|
Amino acid modifications
|Lipidation||2||1||N-myristoyl glycine; by host By similarity|
|Glycosylation||309||1||N-linked (GlcNAc...); by host By similarity|
|Alternative sequence||1 – 163||163||Missing in isoform S.||VSP_031410|
|||"Sequence analysis of HBV genomes isolated from patients with HBsAg negative chronic liver disease."|
Lai M.E., Mazzoleni A.P., Balestrieri A., Melis A., Porru A.
Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Functions of the large hepatitis B virus surface protein in viral particle morphogenesis."|
Bruss V., Gerhardt E., Vieluf K., Wunderlich G.
Intervirology 39:23-31(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Role of glycan processing in hepatitis B virus envelope protein trafficking."|
Block T.M., Lu X., Mehta A., Park J., Blumberg B.S., Dwek R.
Adv. Exp. Med. Biol. 435:207-216(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Envelopment of the hepatitis B virus nucleocapsid."|
Virus Res. 106:199-209(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis."|
Wang H.C., Huang W., Lai M.D., Su I.J.
Cancer Sci. 97:683-688(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
Hepatitis virus B database
|X65258 Genomic DNA. Translation: CAA46353.1.|
3D structure databases
Protocols and materials databases
Family and domain databases
|InterPro||IPR000349. Hepvir_surfAg. |
|Pfam||PF00695. vMSA. 1 hit. |
|Accession||Primary (citable) accession number: Q67875|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families