P17399 (HBSAG_HBVB4) 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 B/C subtype adw (isolate Okinawa/pODW282/1998) (HBV-B) [Complete proteome]

Taxonomic identifier

10415 [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.
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: P17399-1)

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: P17399-2)

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: P17399-3)

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_0000038103
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; Note=In external conformation; Potential
	Topological domain	192 – 242	51	Cytoplasmic; in external conformation Potential
	Transmembrane	243 – 263	21	Helical; Potential
	Topological domain	264 – 337	74	Extracellular Potential
	Transmembrane	338 – 358	21	Helical; 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_031373
	Alternative sequence	1 – 108	108	Missing in isoform M.		VSP_031374

Sequences

	Sequence		Length	Mass (Da)
	Isoform L (Large envelope protein) (LHB) (L-HBsAg) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: CECAC0DDA3D84A10	FASTA	389	42,408
	10 20 30 40 50 60 MGTNLSVPNP LGFFPDHQLD PAFKANSENP DWDLNPNKDN WPDANKVGVG AFGPGFTPPH 70 80 90 100 110 120 GGLLGWSPQA QGLLTTVPAA PPPASTNRQS GRQPTPLSPP LRDTHPQAMQ WNSTTFHQTL 130 140 150 160 170 180 QDPGVRALYF PAGGSSSGTV SPAQNTVSAI SSILSKTGDP VPNMENIASG LLGPLLVLQA 190 200 210 220 230 240 GFFLLTKILT IPQSLDSWWT SLNFLGGTPV CLGQNSQSQI SSHSPTCCPP ICPGYRWMCL 250 260 270 280 290 300 RRFIIFLCIL LLCLIFLLVL LDYQGMLPVC PLIPGSSTTS TGPCKTCTTP AQGTSMFPSC 310 320 330 340 350 360 CCTKPTDGNC TCIPIPSSWA FAKYLWEWAS VRFSWLSLLV PFVQWFVGLS PTVWLSVIWM 370 380 IWFWGPSLYN ILSPFMPLLP IFFCLWVYI
	Isoform M (Middle envelope protein) (MHB) (M-HBsAg) [UniParc]. Checksum: 7AD1CD851F4F0764	FASTA	281	31,020
	10 20 30 40 50 60 MQWNSTTFHQ TLQDPGVRAL YFPAGGSSSG TVSPAQNTVS AISSILSKTG DPVPNMENIA 70 80 90 100 110 120 SGLLGPLLVL QAGFFLLTKI LTIPQSLDSW WTSLNFLGGT PVCLGQNSQS QISSHSPTCC 130 140 150 160 170 180 PPICPGYRWM CLRRFIIFLC ILLLCLIFLL VLLDYQGMLP VCPLIPGSST TSTGPCKTCT 190 200 210 220 230 240 TPAQGTSMFP SCCCTKPTDG NCTCIPIPSS WAFAKYLWEW ASVRFSWLSL LVPFVQWFVG 250 260 270 280 LSPTVWLSVI WMIWFWGPSL YNILSPFMPL LPIFFCLWVY I
	Isoform S (Small envelope protein) (SHB) (S-HBsAg) [UniParc]. Checksum: 7671F4B3CC5D9E7E	FASTA	226	25,330
	10 20 30 40 50 60 MENIASGLLG PLLVLQAGFF LLTKILTIPQ SLDSWWTSLN FLGGTPVCLG QNSQSQISSH 70 80 90 100 110 120 SPTCCPPICP GYRWMCLRRF IIFLCILLLC LIFLLVLLDY QGMLPVCPLI PGSSTTSTGP 130 140 150 160 170 180 CKTCTTPAQG TSMFPSCCCT KPTDGNCTCI PIPSSWAFAK YLWEWASVRF SWLSLLVPFV 190 200 210 220 QWFVGLSPTV WLSVIWMIWF WGPSLYNILS PFMPLLPIFF CLWVYI

References

[1]	"Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes." Okamoto H., Tsuda F., Sakugawa H., Sastrosoewignjo R.I., Imai M., Miyakawa Y., Mayumi M. J. Gen. Virol. 69:2575-2583(1988) [PubMed: 3171552] [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	D00330 Genomic DNA. No translation available.
PIR	SAVLJ2. H28925.
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_HBVB4

Accession

Primary (citable) accession number: P17399

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	May 31, 2011
This is version 55 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program