Q8JMZ6 (HBSAG_HBVH3) 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 H subtype adw4 (isolate Nicaragua/2928Nic/1997) (HBV-H) [Complete proteome]

Taxonomic identifier

489541 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus › Hepatitis B virus › HBV genotype H

Virus host

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

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-terminally 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 Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
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	viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via caveolae-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW
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: Q8JMZ6-1)

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: Q8JMZ6-2)

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: Q8JMZ6-3)

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_0000319098
Regions
	Topological domain	2 – 253	252	Intravirion; in internal conformation Potential
	Topological domain	2 – 181	180	Virion surface; in external conformation Potential
	Transmembrane	182 – 202	21	Helical; Note=In external conformation; Potential
	Topological domain	203 – 253	51	Intravirion; in external conformation Potential
	Transmembrane	254 – 274	21	Helical; Potential
	Topological domain	275 – 348	74	Virion surface Potential
	Transmembrane	349 – 369	21	Helical; Potential
	Topological domain	370 – 375	6	Intravirion Potential
	Transmembrane	376 – 398	23	Helical; Potential
	Topological domain	399 – 400	2	Virion surface 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_031433
	Alternative sequence	1 – 119	119	Missing in isoform M.		VSP_031434

Sequences

	Sequence		Length	Mass (Da)
	Isoform L (Large envelope protein) (LHB) (L-HBsAg) [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 5E24A485875B3B73	FASTA	400	43,729
	10 20 30 40 50 60 MGAPLSTARR GMGQNLSVPN PLGFFPDHQL DPLFRANSSS PDWDFNTNKD NWPMANKVGV 70 80 90 100 110 120 GGFGPGFTPP HGGLLGWSPQ AQGILTTSPP DPPPASTNRR SGRKPTPVSP PLRDTHPQAM 130 140 150 160 170 180 QWNSTQFHQA LLDPRVRGLY LPAGGSSSET QNPVPTIASL TSSIFSKTGD PAMNMENITS 190 200 210 220 230 240 GLLGPLLVLQ AVCFLLTKIL TIPQSLDSWW TSLNFLGVPP GCPGQNSQSP ISNHLPTSCP 250 260 270 280 290 300 PTCPGYRWMC LRRFIIFLFI LLLCLIFLLV LLDYQGMLPV CPLLPGSTTT STGPCKTCTT 310 320 330 340 350 360 LAQGTSMFPS CCCTKPSDGN CTCIPIPSSW AFGKYLWEWA SARFSWLSLL VQFVQWCVGL 370 380 390 400 SPTVWLLVIW MIWYWGPNLC SILSPFIPLL PIFCYLWASI
	Isoform M (Middle envelope protein) (MHB) (M-HBsAg) [UniParc]. Checksum: 18C82E9946BE992F	FASTA	281	31,102
	10 20 30 40 50 60 MQWNSTQFHQ ALLDPRVRGL YLPAGGSSSE TQNPVPTIAS LTSSIFSKTG DPAMNMENIT 70 80 90 100 110 120 SGLLGPLLVL QAVCFLLTKI LTIPQSLDSW WTSLNFLGVP PGCPGQNSQS PISNHLPTSC 130 140 150 160 170 180 PPTCPGYRWM CLRRFIIFLF ILLLCLIFLL VLLDYQGMLP VCPLLPGSTT TSTGPCKTCT 190 200 210 220 230 240 TLAQGTSMFP SCCCTKPSDG NCTCIPIPSS WAFGKYLWEW ASARFSWLSL LVQFVQWCVG 250 260 270 280 LSPTVWLLVI WMIWYWGPNL CSILSPFIPL LPIFCYLWAS I
	Isoform S (Small envelope protein) (SHB) (S-HBsAg) [UniParc]. Checksum: 09D06C984A6E576D	FASTA	226	25,213
	10 20 30 40 50 60 MENITSGLLG PLLVLQAVCF LLTKILTIPQ SLDSWWTSLN FLGVPPGCPG QNSQSPISNH 70 80 90 100 110 120 LPTSCPPTCP GYRWMCLRRF IIFLFILLLC LIFLLVLLDY QGMLPVCPLL PGSTTTSTGP 130 140 150 160 170 180 CKTCTTLAQG TSMFPSCCCT KPSDGNCTCI PIPSSWAFGK YLWEWASARF SWLSLLVQFV 190 200 210 220 QWCVGLSPTV WLLVIWMIWY WGPNLCSILS PFIPLLPIFC YLWASI

References

[1]	"Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America." Arauz-Ruiz P., Norder H., Robertson B.H., Magnius L.O. J. Gen. Virol. 83:2059-2073(2002) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: REVIEW.
[4]	"Envelopment of the hepatitis B virus nucleocapsid." Bruss V. Virus Res. 106:199-209(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY090457 Genomic DNA. Translation: AAM09052.1.
PIR	JQ2119. JQ2120. JQ2121. JQ2122.
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_HBVH3

Accession

Primary (citable) accession number: Q8JMZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	October 1, 2002
Last modified:	April 3, 2013
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program