ID   HBSAG_HBVD6             Reviewed;         389 AA.
AC   Q67875;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-NOV-2023, entry version 80.
DE   RecName: Full=Large envelope protein {ECO:0000255|HAMAP-Rule:MF_04075};
DE   AltName: Full=L glycoprotein {ECO:0000255|HAMAP-Rule:MF_04075};
DE   AltName: Full=L-HBsAg {ECO:0000255|HAMAP-Rule:MF_04075};
DE            Short=LHB {ECO:0000255|HAMAP-Rule:MF_04075};
DE   AltName: Full=Large S protein {ECO:0000255|HAMAP-Rule:MF_04075};
DE   AltName: Full=Large surface protein {ECO:0000255|HAMAP-Rule:MF_04075};
DE   AltName: Full=Major surface antigen {ECO:0000255|HAMAP-Rule:MF_04075};
GN   Name=S {ECO:0000255|HAMAP-Rule:MF_04075};
OS   Hepatitis B virus genotype D subtype ayw (isolate Italy/CI/1992) (HBV-D).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Blubervirales; Hepadnaviridae; Orthohepadnavirus; Hepatitis B virus;
OC   hepatitis B virus genotype D.
OX   NCBI_TaxID=489489;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Lai M.E., Mazzoleni A.P., Balestrieri A., Melis A., Porru A.;
RT   "Sequence analysis of HBV genomes isolated from patients with HBsAg
RT   negative chronic liver disease.";
RL   Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   REVIEW.
RX   PubMed=8957666; DOI=10.1159/000150471;
RA   Bruss V., Gerhardt E., Vieluf K., Wunderlich G.;
RT   "Functions of the large hepatitis B virus surface protein in viral particle
RT   morphogenesis.";
RL   Intervirology 39:23-31(1996).
RN   [3]
RP   REVIEW.
RX   PubMed=9498079; DOI=10.1007/978-1-4615-5383-0_20;
RA   Block T.M., Lu X., Mehta A., Park J., Blumberg B.S., Dwek R.;
RT   "Role of glycan processing in hepatitis B virus envelope protein
RT   trafficking.";
RL   Adv. Exp. Med. Biol. 435:207-216(1998).
RN   [4]
RP   REVIEW.
RX   PubMed=15567498; DOI=10.1016/j.virusres.2004.08.016;
RA   Bruss V.;
RT   "Envelopment of the hepatitis B virus nucleocapsid.";
RL   Virus Res. 106:199-209(2004).
RN   [5]
RP   REVIEW.
RX   PubMed=16863502; DOI=10.1111/j.1349-7006.2006.00235.x;
RA   Wang H.C., Huang W., Lai M.D., Su I.J.;
RT   "Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and
RT   hepatocarcinogenesis.";
RL   Cancer Sci. 97:683-688(2006).
CC   -!- FUNCTION: The large envelope protein exists in two topological
CC       conformations, one which is termed 'external' or Le-HBsAg and the other
CC       'internal' or Li-HBsAg. In its external conformation the protein
CC       attaches the virus to cell receptors and thereby initiating infection.
CC       This interaction determines the species specificity and liver tropism.
CC       This attachment induces virion internalization predominantly through
CC       caveolin-mediated endocytosis. The large envelope protein also assures
CC       fusion between virion membrane and endosomal membrane. In its internal
CC       conformation the protein plays a role in virion morphogenesis and
CC       mediates the contact with the nucleocapsid like a matrix protein.
CC       {ECO:0000255|HAMAP-Rule:MF_04075}.
CC   -!- FUNCTION: The middle envelope protein plays an important role in the
CC       budding of the virion. It is involved in the induction of budding in a
CC       nucleocapsid independent way. In this process the majority of envelope
CC       proteins bud to form subviral lipoprotein particles of 22 nm of
CC       diameter that do not contain a nucleocapsid. {ECO:0000255|HAMAP-
CC       Rule:MF_04075}.
CC   -!- SUBUNIT: Li-HBsAg interacts with capsid protein and with HDV Large
CC       delta antigen. Isoform M associates with host chaperone CANX through
CC       its pre-S2 N glycan. This association may be essential for M proper
CC       secretion. {ECO:0000255|HAMAP-Rule:MF_04075}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC       Rule:MF_04075}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing, Alternative initiation; Named isoforms=2;
CC       Name=L; Synonyms=Large envelope protein, LHB, L-HBsAg;
CC         IsoId=Q67875-1; Sequence=Displayed;
CC       Name=S; Synonyms=Small envelope protein, SHB, S-HBsAg;
CC         IsoId=Q67875-2; Sequence=VSP_031410;
CC   -!- DOMAIN: The large envelope protein is synthesized with the pre-S region
CC       at the cytosolic side of the endoplasmic reticulum and, hence will be
CC       within the virion after budding. Therefore the pre-S region is not N-
CC       glycosylated. Later a post-translational translocation of N-terminal
CC       pre-S and TM1 domains occur in about 50% of proteins at the virion
CC       surface. These molecules change their topology by an unknown mechanism,
CC       resulting in exposure of pre-S region at virion surface.
CC   -!- DOMAIN: The large envelope protein is synthesized with the pre-S region
CC       at the cytosolic side of the endoplasmic reticulum and, hence will be
CC       within the virion after budding. Therefore the pre-S region is not N-
CC       glycosylated. Later a post-translational translocation of N-terminal
CC       pre-S and TM1 domains occur in about 50% of proteins at the virion
CC       surface. These molecules change their topology by an unknown mechanism,
CC       resulting in exposure of pre-S region at virion surface. For isoform M
CC       in contrast, the pre-S2 region is translocated cotranslationally to the
CC       endoplasmic reticulum lumen and is N-glycosylated. {ECO:0000255|HAMAP-
CC       Rule:MF_04075}.
CC   -!- PTM: Isoform M is N-terminally acetylated by host at a ratio of 90%,
CC       and N-glycosylated by host at the pre-S2 region. {ECO:0000255|HAMAP-
CC       Rule:MF_04075}.
CC   -!- PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04075}.
CC   -!- BIOTECHNOLOGY: Systematic vaccination of individuals at risk of
CC       exposure to the virus has been the main method of controlling the
CC       morbidity and mortality associated with hepatitis B. The first
CC       hepatitis B vaccine was manufactured by the purification and
CC       inactivation of HBsAg obtained from the plasma of chronic hepatitis B
CC       virus carriers. The vaccine is now produced by recombinant DNA
CC       techniques and expression of the S isoform in yeast cells. The pre-S
CC       region do not seem to induce strong enough antigenic response.
CC   -!- SIMILARITY: Belongs to the orthohepadnavirus major surface antigen
CC       family. {ECO:0000255|HAMAP-Rule:MF_04075}.
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DR   EMBL; X65258; CAA46353.1; -; Genomic_DNA.
DR   PIR; JQ2054; JQ2054.
DR   PIR; S20749; S20749.
DR   GlyCosmos; Q67875; 1 site, No reported glycans.
DR   Proteomes; UP000008282; Genome.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0075513; P:caveolin-mediated endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   HAMAP; MF_04075; HBV_HBSAG; 1.
DR   InterPro; IPR000349; HBV_HBSAG.
DR   Pfam; PF00695; vMSA; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative initiation; Alternative splicing;
KW   Caveolin-mediated endocytosis of virus by host;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host-virus interaction; Lipoprotein; Membrane; Myristate; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   CHAIN           2..389
FT                   /note="Large envelope protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT                   /id="PRO_0000319087"
FT   TOPO_DOM        2..242
FT                   /note="Intravirion; in internal conformation"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TOPO_DOM        2..170
FT                   /note="Virion surface; in external conformation"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TRANSMEM        171..191
FT                   /note="Helical; Name=TM1; Note=In external conformation"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TOPO_DOM        192..242
FT                   /note="Intravirion; in external conformation"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TRANSMEM        243..263
FT                   /note="Helical; Name=TM2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TOPO_DOM        264..337
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TRANSMEM        338..358
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TOPO_DOM        359..364
FT                   /note="Intravirion"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TRANSMEM        365..387
FT                   /note="Helical; Name=TM3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   TOPO_DOM        388..389
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   REGION          1..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2..163
FT                   /note="Pre-S"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   REGION          2..108
FT                   /note="Pre-S1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   REGION          73..106
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          109..163
FT                   /note="Pre-S2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   COMPBIAS        80..97
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   CARBOHYD        309
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT   VAR_SEQ         1..163
FT                   /note="Missing (in isoform S)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_031410"
SQ   SEQUENCE   389 AA;  42661 MW;  A39542B416E48F24 CRC64;
     MGQNLSTSNP LGFFPDHQLD PASRANTANP DWDFNPNKDT WPDANKDGAG AFGLGLTPPH
     GGLLGWSPQA QGILHTVPAN PPPASTNRQT GRQPTPLSPP LRDTHPQAVQ WNSTTFHQTL
     QDPRVRGLYF PAGGSSSGTV NPVPTTASPL SSIFSRIGDP VTNMENITSG FLGPLLVLQA
     GFFLLTRILT IPQSLDSWWT SLNFRGGTTV CLGQNSQSPT SNHSPTSCPP TCPGYRWMCL
     RGFIIFLFIL LLCLIFLLVL LEYQGMLHVC PLIPGTTTTS TGPCKTCTTP AQGNSMFPSC
     CCTKTSDGNC TCIPIPSSWA FAKYLWEWAS VRFSWLSLLV PFVQWFVGLS PTVWLSAIWM
     MWYWGPSLYS ILSPFLPLLP IFFCLWVYI
//