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Protein

Large envelope protein

Gene

S

Organism
Hepatitis B virus genotype E subtype ayw4 (isolate Kou) (HBV-E)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

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 assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein.UniRule annotation
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.UniRule annotation

GO - Biological processi

Keywordsi

Biological processCaveolin-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

Names & Taxonomyi

Protein namesi
Recommended name:
Large envelope proteinUniRule annotation
Alternative name(s):
L glycoproteinUniRule annotation
L-HBsAgUniRule annotation
Short name:
LHBUniRule annotation
Large S proteinUniRule annotation
Large surface proteinUniRule annotation
Major surface antigenUniRule annotation
Gene namesi
Name:SUniRule annotation
OrganismiHepatitis B virus genotype E subtype ayw4 (isolate Kou) (HBV-E)
Taxonomic identifieri489495 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesHepadnaviridaeOrthohepadnavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Pan troglodytes (Chimpanzee) [TaxID: 9598]
Proteomesi
  • UP000008538 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 252Intravirion; in internal conformationUniRule annotationAdd BLAST251
Topological domaini2 – 180Virion surface; in external conformationUniRule annotationAdd BLAST179
Transmembranei181 – 201Helical; Name=TM1; Note=In external conformationUniRule annotationAdd BLAST21
Topological domaini202 – 252Intravirion; in external conformationUniRule annotationAdd BLAST51
Transmembranei253 – 273Helical; Name=TM2UniRule annotationAdd BLAST21
Topological domaini274 – 347Virion surfaceUniRule annotationAdd BLAST74
Transmembranei348 – 368HelicalUniRule annotationAdd BLAST21
Topological domaini369 – 374IntravirionUniRule annotation6
Transmembranei375 – 397Helical; Name=TM3UniRule annotationAdd BLAST23
Topological domaini398 – 399Virion surfaceUniRule annotation2

GO - Cellular componenti

Keywords - Cellular componenti

Membrane, Virion

Pathology & Biotechi

Biotechnological usei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostUniRule annotation
ChainiPRO_00003190892 – 399Large envelope proteinUniRule annotationAdd BLAST398

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostUniRule annotation1
Glycosylationi319N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Isoform M (identifier: Q69603-2)
Modified residuei1N-acetylmethionineBy similarity1
Glycosylationi4N-linked (GlcNAc...) asparagineBy similarity1

Post-translational modificationi

Isoform M is N-terminally acetylated by host at a ratio of 90%, and N-glycosylated by host at the pre-S2 region.UniRule annotationBy similarity
Myristoylated.UniRule annotation

Keywords - PTMi

Acetylation, Glycoprotein, Lipoprotein, Myristate

Interactioni

Subunit structurei

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.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliQ69603.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 173Pre-SUniRule annotationAdd BLAST172
Regioni2 – 118Pre-S1UniRule annotationAdd BLAST117
Regioni119 – 173Pre-S2UniRule annotationAdd BLAST55

Domaini

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.UniRule annotation

Sequence similaritiesi

Belongs to the orthohepadnavirus major surface antigen family.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG090000AH.

Family and domain databases

HAMAPiMF_04075. HBV_HBSAG. 1 hit.
InterProiView protein in InterPro
IPR000349. Hepvir_surfAg.
PfamiView protein in Pfam
PF00695. vMSA. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform L (identifier: Q69603-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGLSWTVPLE WGKNISTTNP LGFFPDHQLD PAFRANTRNP DWDHNPNKDH
60 70 80 90 100
WTEANKVGVG AFGPGFTPPH GGLLGWSPQA QGMLKTLPAD PPPASTNRQS
110 120 130 140 150
GRQPTPITPP LRDTHPQAMQ WNSTTFHQAL QDPRVRGLYF PAGGSSSGTV
160 170 180 190 200
NPVPTTASLI SSIFSRIGDP APNMESITSG FLGPLLVLQA GFFLLTKILT
210 220 230 240 250
IPQSLDSWWT SLNFLGGAPV CLGQNSQSPT SNHSPTSCPP ICPGYRWMCL
260 270 280 290 300
RRFIIFLFIL LLCLIFLLVL LDYQGMLPVC PLIPGSSTTS TGPCRTCMTL
310 320 330 340 350
AQGTSMFPSC CCSKPSDGNC TCIPIPSSWA FGKFLWEWAS ARFSWLSLLV
360 370 380 390
PFVQWFAGLS PTVWLSVIWM MWYWGPSLYD ILSPFIPLLP IFFCLWVYI
Length:399
Mass (Da):43,984
Last modified:February 26, 2008 - v2
Checksum:i79B52A0B9A55DB73
GO
Isoform M (identifier: Q69603-2) [UniParc]FASTAAdd to basket
Also known as: Middle envelope protein, MHB, M-HBsAg

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Show »
Length:281
Mass (Da):31,142
Checksum:iEB38F7A010DF4C9E
GO
Isoform S (identifier: Q69603-3) [UniParc]FASTAAdd to basket
Also known as: Small envelope protein, SHB, S-HBsAg

The sequence of this isoform differs from the canonical sequence as follows:
     1-173: Missing.

Show »
Length:226
Mass (Da):25,326
Checksum:iFD0E70C563B11992
GO

Sequence cautioni

The sequence CAA53355 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0314131 – 173Missing in isoform S. CuratedAdd BLAST173
Alternative sequenceiVSP_0314141 – 118Missing in isoform M. CuratedAdd BLAST118

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75664 Genomic DNA. Translation: CAA53355.1. Different initiation.
PIRiJQ1578.
JQ2079.
JQ2087.
JQ2088.
JQ2089.
JQ2091.
JQ2092.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHBSAG_HBVE1
AccessioniPrimary (citable) accession number: Q69603
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: July 5, 2017
This is version 67 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families