P03144 (HBSAG_GSHV) 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

Ground squirrel hepatitis virus (strain 27) (GSHV) [Complete proteome]

Taxonomic identifier

10406 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus

Virus host

Spermophilus [TaxID: 9996]

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

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. The large envelope protein probably also assumes fusion between virion and host membranes. 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.
Sequence similarities	Belongs to the orthohepadnavirus major surface antigen family.
Sequence caution	The sequence AAA46757.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Fusion of virus membrane with host membrane Host-virus interaction Initiation of viral infection Viral attachment to host cell Viral penetration into host cytoplasm
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: P03144-1)

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: P03144-2)

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

The sequence of this isoform differs from the canonical sequence as follows:
     1-146: Missing.

Isoform S (identifier: P03144-3)

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

The sequence of this isoform differs from the canonical sequence as follows:
     1-206: 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 – 428	427	Large envelope protein		PRO_0000038083
Regions
	Topological domain	4 – 283	280	Cytoplasmic; in internal conformation Potential
	Topological domain	4 – 211	208	Extracellular; in external conformation Potential
	Transmembrane	212 – 232	21	Helical; Name=TM1; Note=In external conformation; Potential
	Topological domain	233 – 283	51	Cytoplasmic; in external conformation Potential
	Transmembrane	284 – 304	21	Helical; Name=TM2; Potential
	Topological domain	305 – 376	72	Extracellular Potential
	Transmembrane	377 – 397	21	Helical; Name=TM3; Potential
	Topological domain	398 – 403	6	Cytoplasmic Potential
	Transmembrane	404 – 426	23	Helical; Potential
	Topological domain	427 – 428	2	Extracellular Potential
	Region	2 – 206	205	Pre-S By similarity
	Region	2 – 146	145	Pre-S1 By similarity
	Region	147 – 206	60	Pre-S2 By similarity
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
	Glycosylation	149	1	N-linked (GlcNAc...); by host; in isoform M By similarity
	Glycosylation	348	1	N-linked (GlcNAc...); by host By similarity
Natural variations
	Alternative sequence	1 – 206	206	Missing in isoform S.		VSP_031448
	Alternative sequence	1 – 146	146	Missing in isoform M.		VSP_031449

Sequences

	Sequence		Length	Mass (Da)
	Isoform L (Large envelope protein) (LHB) (L-HBsAg) [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 5E84114BC33862D7	FASTA	428	48,383
	10 20 30 40 50 60 MGNNIKVTFD PNKLAAWWPT VGTYYTPTTT VTNPAIFKPG IYQTTSLKNP KNQQELDAIL 70 80 90 100 110 120 MTRYKEIDWD NWQGFPVNQR LPVSNNNPPS GQRAETFEIK SRPIIVPGIR DIPRGIVPPQ 130 140 150 160 170 180 TPSNRDQRRK PTPLTPPLRD THPHLTMKNQ TGHLQGFAEG LRALTTSDHH NSAYGDPFTT 190 200 210 220 230 240 LSPVVPTVST TLSPPLTIGD PVLSTEMSPS GLLGLLAGLQ VVYFLWTKIL TIAQSLDWWW 250 260 270 280 290 300 TSLSFPGGIP ECTGQNLQFQ TCKHLPTSCP PTCNGFRWMY LRRFIIYLLV LLLFLTFLLV 310 320 330 340 350 360 LLDWKGLLPV CPMMPATETT VNCRQCTISA QDTFTTPYCC CLKPTAGNCT CWPIPSSWAL 370 380 390 400 410 420 GSYLWEWALA RFSWLSLLVP LLQWLGGISL TVWLLLIWMI WFWGPVLMSI LPPFIPIFAL FFLIWAYI
	Isoform M (Middle envelope protein) (MHB) (M-HBsAg) [UniParc]. Checksum: A82E58360A5DDFDF	FASTA	282	31,764
	10 20 30 40 50 60 MKNQTGHLQG FAEGLRALTT SDHHNSAYGD PFTTLSPVVP TVSTTLSPPL TIGDPVLSTE 70 80 90 100 110 120 MSPSGLLGLL AGLQVVYFLW TKILTIAQSL DWWWTSLSFP GGIPECTGQN LQFQTCKHLP 130 140 150 160 170 180 TSCPPTCNGF RWMYLRRFII YLLVLLLFLT FLLVLLDWKG LLPVCPMMPA TETTVNCRQC 190 200 210 220 230 240 TISAQDTFTT PYCCCLKPTA GNCTCWPIPS SWALGSYLWE WALARFSWLS LLVPLLQWLG 250 260 270 280 GISLTVWLLL IWMIWFWGPV LMSILPPFIP IFALFFLIWA YI
	Isoform S (Small envelope protein) (SHB) (S-HBsAg) [UniParc]. Checksum: B44662CA25AEF543	FASTA	222	25,475
	10 20 30 40 50 60 MSPSGLLGLL AGLQVVYFLW TKILTIAQSL DWWWTSLSFP GGIPECTGQN LQFQTCKHLP 70 80 90 100 110 120 TSCPPTCNGF RWMYLRRFII YLLVLLLFLT FLLVLLDWKG LLPVCPMMPA TETTVNCRQC 130 140 150 160 170 180 TISAQDTFTT PYCCCLKPTA GNCTCWPIPS SWALGSYLWE WALARFSWLS LLVPLLQWLG 190 200 210 220 GISLTVWLLL IWMIWFWGPV LMSILPPFIP IFALFFLIWA YI

References

[1]	"Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus." Seeger C., Ganem D., Varmus H.E. J. Virol. 51:367-375(1984) [PubMed: 6086950] [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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	K02715 Genomic DNA. Translation: AAA46757.1. Different initiation.
PIR	SAVLS. A03709.
RefSeq	NP_040995.1. NC_001484.1. NP_955537.1. NC_001484.1.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1488458.
Family and domain databases
InterPro	IPR000349. Hepvir_surfAg. [Graphical view]
Pfam	PF00695. vMSA. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

HBSAG_GSHV

Accession

Primary (citable) accession number: P03144

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 31, 2011
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program