O91534 (HBSAG_HBVA7) 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 (isolate Japan/11D11HCCW/1998) (HBV-A) [Complete proteome]

Taxonomic identifier

489457 [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	400 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.
Subunit structure	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.
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.

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: O91534-1)

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: O91534-2)

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

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Isoform S (identifier: O91534-3)

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

The sequence of this isoform differs from the canonical sequence as follows:
     1-174: 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 – 400	399	Large envelope protein		PRO_0000319072
Regions
	Topological domain	2 – 253	252	Cytoplasmic; in internal conformation Potential
	Topological domain	2 – 181	180	Extracellular; in external conformation Potential
	Transmembrane	182 – 202	21	Helical; Name=TM1; Note=In external conformation; Potential
	Topological domain	203 – 253	51	Cytoplasmic; in external conformation Potential
	Transmembrane	254 – 274	21	Helical; Name=TM2; Potential
	Topological domain	275 – 348	74	Extracellular Potential
	Transmembrane	349 – 369	21	Helical; Name=TM3; Potential
	Topological domain	370 – 375	6	Cytoplasmic Potential
	Transmembrane	376 – 398	23	Helical; Potential
	Topological domain	399 – 400	2	Extracellular Potential
	Region	2 – 174	173	Pre-S
	Region	2 – 119	118	Pre-S1
	Region	120 – 174	55	Pre-S2
Amino acid modifications
	Modified residue	120	1	N-acetylmethionine; by host; in isoform M By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
	Glycosylation	123	1	N-linked (GlcNAc...); by host; in isoform M By similarity
	Glycosylation	320	1	N-linked (GlcNAc...); by host By similarity
Natural variations
	Alternative sequence	1 – 174	174	Missing in isoform S.		VSP_031362
	Alternative sequence	1 – 119	119	Missing in isoform M.		VSP_031363

Sequences

	Sequence		Length	Mass (Da)
	Isoform L (Large envelope protein) (LHB) (L-HBsAg) [UniParc]. Last modified November 1, 1998. Version 1. Checksum: A4D0C9B477283DE7	FASTA	400	43,729
	10 20 30 40 50 60 MGGWSSKPRK GMGTNLSVPN PLGFFPDHQL DPAFGANSNN PDWDFNPIKD HWPAANQVGV 70 80 90 100 110 120 GAFGPGFTPP HGGILGWSPQ AQGILTTVST IPPPASTNRQ SGRQPTPISP PLRDSHPQAM 130 140 150 160 170 180 QWNSTAFHQT LQDPRVRGLY LPAGGSSSGT VNPAPNIASH ISSISARTGD PVTNMENITS 190 200 210 220 230 240 GFLGPLLVLQ AGFFLLTRIL TIPQSLDSWW TSLNFLGGSP VCLGQNSQSP TSNHSPTSCP 250 260 270 280 290 300 PICPGYRWMC LRRFIIFLFI LLLCLIFLLV LLDYQGMLPV CPLIPGSTTT STGPCKTCTT 310 320 330 340 350 360 PAQGNSMFPS CCCTKPTDGN CTCIPIPSSW AFAKFLWEWA SVRFSWLSLL VPFVQWFVGL 370 380 390 400 SPTVWLSAIW MMWYWGPSLY SIVRPFIPLL PIFFCLWVYI
	Isoform M (Middle envelope protein) (MHB) (M-HBsAg) [UniParc]. Checksum: 544531BD81E27D42	FASTA	281	31,194
	10 20 30 40 50 60 MQWNSTAFHQ TLQDPRVRGL YLPAGGSSSG TVNPAPNIAS HISSISARTG DPVTNMENIT 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 TPAQGNSMFP SCCCTKPTDG NCTCIPIPSS WAFAKFLWEW ASVRFSWLSL LVPFVQWFVG 250 260 270 280 LSPTVWLSAI WMMWYWGPSL YSIVRPFIPL LPIFFCLWVY I
	Isoform S (Small envelope protein) (SHB) (S-HBsAg) [UniParc]. Checksum: 885DF4693FC683DC	FASTA	226	25,447
	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 NSMFPSCCCT KPTDGNCTCI PIPSSWAFAK FLWEWASVRF SWLSLLVPFV 190 200 210 220 QWFVGLSPTV WLSAIWMMWY WGPSLYSIVR PFIPLLPIFF CLWVYI

References

[1]	"Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates." Takahashi K., Akahane Y., Hino K., Ohta Y., Mishiro S. Arch. Virol. 143:2313-2326(1998) [PubMed: 9930189] [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	AB014370 Genomic DNA. Translation: BAA32872.1.
PIR	JQ2045. JQ2046. JQ2047. JQ2048. JQ2050. JQ2051. JQ2053. JQ2054.
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_HBVA7

Accession

Primary (citable) accession number: O91534

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	November 1, 1998
Last modified:	May 31, 2011
This is version 48 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program