P03142 (HBSAG_HBVA2) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Large envelope protein

Alternative name(s):
L glycoprotein
L-HBsAg
Short name=LHB
Large S protein
Large surface protein
Major surface antigen

Gene names

Name:

S

Organism

Hepatitis B virus genotype A2 subtype adw (isolate Japan/Nishioka/1983) (HBV-A) [Complete proteome]

Taxonomic identifier

482134 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus

Virus host

Pan troglodytes (Chimpanzee) [TaxID: 9598]
Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	389 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subcellular location	Virion membrane By similarity.
Domain	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. For isoform M in contrast, the pre-S2 region is translocated cotranslationally to the endoplasmic reticulum lumen and is N-glycosylated.
Post-translational modification	Isoform M is N-terminaly acetylated at a ratio of 90%, and N-glycosylated at the pre-S2 region By similarity. Myristoylated By similarity.
Biotechnological use	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.
Sequence similarities	Belongs to the orthohepadnavirus major surface antigen family.
Sequence caution	The sequence CAA24233.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Caveolin-mediated endocytosis of virus by host Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Host-virus interaction Initiation of viral infection Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host
Cellular component	Membrane Virion
Coding sequence diversity	Alternative initiation Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Acetylation Glycoprotein Lipoprotein Myristate
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW viral reproduction Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform L (identifier: P03142-1)

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 M (identifier: P03142-2)

Also known as: Middle envelope protein; MHB; M-HBsAg;

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Isoform S (identifier: P03142-3)

Also known as: Small envelope protein; SHB; S-HBsAg;

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – 389	388	Large envelope protein		PRO_0000038097
Regions
	Topological domain	2 – 242	241	Cytoplasmic; in internal conformation Potential
	Topological domain	2 – 170	169	Extracellular; in external conformation Potential
	Transmembrane	171 – 191	21	Helical; Name=TM1; Note=In external conformation; Potential
	Topological domain	192 – 242	51	Cytoplasmic; in external conformation Potential
	Transmembrane	243 – 263	21	Helical; Name=TM2; Potential
	Topological domain	264 – 337	74	Extracellular Potential
	Transmembrane	338 – 358	21	Helical; Name=TM3; Potential
	Topological domain	359 – 364	6	Cytoplasmic Potential
	Transmembrane	365 – 387	23	Helical; Potential
	Topological domain	388 – 389	2	Extracellular Potential
	Region	2 – 163	162	Pre-S
	Region	2 – 108	107	Pre-S1
	Region	109 – 163	55	Pre-S2
Amino acid modifications
	Modified residue	109	1	N-acetylmethionine; by host; in isoform M By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
	Glycosylation	112	1	N-linked (GlcNAc...); by host; in isoform M By similarity
	Glycosylation	309	1	N-linked (GlcNAc...); by host By similarity
Natural variations
	Alternative sequence	1 – 163	163	Missing in isoform S.		VSP_031354
	Alternative sequence	1 – 108	108	Missing in isoform M.		VSP_031355

Sequences

	Sequence		Length	Mass (Da)
	Isoform L (Large envelope protein) (LHB) (L-HBsAg) [UniParc]. Last modified January 23, 2007. Version 4. Checksum: FE9EF2E7EEFC58B5	FASTA	389	42,354
	10 20 30 40 50 60 MGTNLSVPNP LGFLPDHQLD PAFGANSTNP DWDFNPIKDH WPAANQVGVG AFGPGLTPPH 70 80 90 100 110 120 GGILGWSPQA QGILTTVSTI PPPASTNRQS GRQPTPISPP LRDSHPQAMQ WNSTALHQAL 130 140 150 160 170 180 QDPRVRGLYL PAGGSSSGTV NPAPNIASHI SSISARTGDP VTIMENITSG FLGPLLVLQA 190 200 210 220 230 240 GFFLLTRILT IPQSLDSWWT SLNFLGGSPV CLGQNSQSPT SNHSPTSCPP ICPGYRWMCL 250 260 270 280 290 300 RRFIIFLFIL LLCLIFLLVL LDYQGMLPVC PLIPGSTTTS TGPCKTCTTP AQGNSKFPSC 310 320 330 340 350 360 CCTKPTDGNC TCIPIPSSWA FAKYLWEWAS VRFSWLSLLV PFVQWFVGLS PTVWLSAIWM 370 380 MWYWGPSLYS IVSPFIPLLP IFFCLWVYI
	Isoform M (Middle envelope protein) (MHB) (M-HBsAg) [UniParc]. Checksum: 8C43853A80BE789D	FASTA	281	31,073
	10 20 30 40 50 60 MQWNSTALHQ ALQDPRVRGL YLPAGGSSSG TVNPAPNIAS HISSISARTG DPVTIMENIT 70 80 90 100 110 120 SGFLGPLLVL QAGFFLLTRI LTIPQSLDSW WTSLNFLGGS PVCLGQNSQS PTSNHSPTSC 130 140 150 160 170 180 PPICPGYRWM CLRRFIIFLF ILLLCLIFLL VLLDYQGMLP VCPLIPGSTT TSTGPCKTCT 190 200 210 220 230 240 TPAQGNSKFP SCCCTKPTDG NCTCIPIPSS WAFAKYLWEW ASVRFSWLSL LVPFVQWFVG 250 260 270 280 LSPTVWLSAI WMMWYWGPSL YSIVSPFIPL LPIFFCLWVY I
	Isoform S (Small envelope protein) (SHB) (S-HBsAg) [UniParc]. Checksum: D3CBA3068D4275DA	FASTA	226	25,391
	10 20 30 40 50 60 MENITSGFLG PLLVLQAGFF LLTRILTIPQ SLDSWWTSLN FLGGSPVCLG QNSQSPTSNH 70 80 90 100 110 120 SPTSCPPICP GYRWMCLRRF IIFLFILLLC LIFLLVLLDY QGMLPVCPLI PGSTTTSTGP 130 140 150 160 170 180 CKTCTTPAQG NSKFPSCCCT KPTDGNCTCI PIPSSWAFAK YLWEWASVRF SWLSLLVPFV 190 200 210 220 QWFVGLSPTV WLSAIWMMWY WGPSLYSIVS PFIPLLPIFF CLWVYI

References

[1]	"The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw." Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. Nucleic Acids Res. 11:1747-1757(1983) [PubMed: 6300776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"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: 8957666] [Abstract] Cited for: REVIEW.
[3]	"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: 9498079] [Abstract] Cited for: REVIEW.
[4]	"Envelopment of the hepatitis B virus nucleocapsid." Bruss V. Virus Res. 106:199-209(2004) [PubMed: 15567498] [Abstract] Cited for: REVIEW.
[5]	"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: 16863502] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBL GenBank DDBJ	V00866 Genomic DNA. Translation: CAA24233.1. Different initiation.
PIR	SAVLVE. A93460.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR000349. Hepvir_surfAg. [Graphical view]
Pfam	PF00695. vMSA. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

HBSAG_HBVA2

Accession

Primary (citable) accession number: P03142

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 31, 2011
This is version 59 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program