HBSAG_HBVA3
ID HBSAG_HBVA3 Reviewed; 400 AA.
AC P03141;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 29-SEP-2021, entry version 87.
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 A2 subtype adw2 (strain Rutter 1979) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=480116;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J.;
RT "The nucleotide sequence of the hepatitis B viral genome and the
RT identification of the major viral genes.";
RL (In) Field B.N., Jaenisch R., Fox C.F. (eds.);
RL Animal virus genetics, pp.57-70, Academic Press, New York (1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 175-400.
RX PubMed=471053; DOI=10.1038/280815a0;
RA Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H.M., Rutter W.J.;
RT "Nucleotide sequence of the gene coding for the major protein of hepatitis
RT B virus surface antigen.";
RL Nature 280:815-819(1979).
RN [3]
RP RECOMBINANT VACCINE.
RX PubMed=6150233; DOI=10.1016/s0140-6736(84)92740-5;
RA Jilg W., Lorbeer B., Schmidt M., Wilske B., Zoulek G., Deinhardt F.;
RT "Clinical evaluation of a recombinant hepatitis B vaccine.";
RL Lancet 2:1174-1175(1984).
RN [4]
RP CHARACTERIZATION.
RC STRAIN=Isolate clinical;
RX PubMed=6492255; DOI=10.1128/jvi.52.2.396-402.1984;
RA Heermann K.H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H.,
RA Gerlich W.H.;
RT "Large surface proteins of hepatitis B virus containing the pre-s
RT sequence.";
RL J. Virol. 52:396-402(1984).
RN [5]
RP FUNCTION.
RX PubMed=2041095; DOI=10.1128/jvi.65.7.3813-3820.1991;
RA Bruss V., Ganem D.;
RT "Mutational analysis of hepatitis B surface antigen particle assembly and
RT secretion.";
RL J. Virol. 65:3813-3820(1991).
RN [6]
RP TRANSMEMBRANE TOPOLOGY.
RX PubMed=8194518; DOI=10.1002/j.1460-2075.1994.tb06509.x;
RA Bruss V., Lu X., Thomssen R., Gerlich W.H.;
RT "Post-translational alterations in transmembrane topology of the hepatitis
RT B virus large envelope protein.";
RL EMBO J. 13:2273-2279(1994).
RN [7]
RP INTERACTION WITH HDV ANTIGENS (ISOFORM S).
RX PubMed=8289368; DOI=10.1128/jvi.68.2.646-653.1994;
RA Chang M.F., Chen C.J., Chang S.C.;
RT "Mutational analysis of delta antigen: effect on assembly and replication
RT of hepatitis delta virus.";
RL J. Virol. 68:646-653(1994).
RN [8]
RP FUNCTION (ISOFORM M).
RX PubMed=9050863; DOI=10.1073/pnas.94.5.1822;
RA Mehta A., Lu X., Block T.M., Blumberg B.S., Dwek R.A.;
RT "Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their
RT sensitivity to glycan processing: evidence that alteration of a single N-
RT linked glycosylation site can regulate HBV secretion.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1822-1827(1997).
RN [9]
RP FUNCTION OF GLYCOSYLATION.
RX PubMed=9122203; DOI=10.1073/pnas.94.6.2380;
RA Lu X., Mehta A., Dadmarz M., Dwek R., Blumberg B.S., Block T.M.;
RT "Aberrant trafficking of hepatitis B virus glycoproteins in cells in which
RT N-glycan processing is inhibited.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2380-2385(1997).
RN [10]
RP INTERACTION WITH HOST CANX (ISOFORM L).
RX PubMed=9188622; DOI=10.1128/jvi.71.7.5487-5494.1997;
RA Xu Z., Bruss V., Yen T.S.;
RT "Formation of intracellular particles by hepatitis B virus large surface
RT protein.";
RL J. Virol. 71:5487-5494(1997).
RN [11]
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 [12]
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 [13]
RP INTERACTION WITH HOST CANX (ISOFORM M).
RX PubMed=9420286; DOI=10.1128/jvi.72.1.778-782.1998;
RA Werr M., Prange R.;
RT "Role for calnexin and N-linked glycosylation in the assembly and secretion
RT of hepatitis B virus middle envelope protein particles.";
RL J. Virol. 72:778-782(1998).
RN [14]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=11350599; DOI=10.1034/j.1399-3011.2001.00848.x;
RA De Falco S., Ruvo M., Verdoliva A., Scarallo A., Raimondo D., Raucci A.,
RA Fassina G.;
RT "N-terminal myristylation of HBV preS1 domain enhances receptor
RT recognition.";
RL J. Pept. Res. 57:390-400(2001).
RN [15]
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 [16]
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).
RN [17]
RP INTERACTION WITH ISOFORM S (ISOFORM L), INTERACTION WITH THE CAPSID
RP PROTEIN, AND INTERACTION WITH ISOFORM L (ISOFORM S).
RX PubMed=31700077; DOI=10.1038/s41598-019-52824-z;
RA Pastor F., Herrscher C., Patient R., Eymieux S., Moreau A.,
RA Burlaud-Gaillard J., Seigneuret F., de Rocquigny H., Roingeard P.,
RA Hourioux C.;
RT "Direct interaction between the hepatitis B virus core and envelope
RT proteins analyzed in a cellular context.";
RL Sci. Rep. 9:16178-16178(2019).
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: [Isoform L]: In its internal form (Li-HBsAg), interacts with
CC the capsid protein and with the isoform S (PubMed:31700077). Interacts
CC with host chaperone CANX (PubMed:9188622).
CC {ECO:0000269|PubMed:31700077, ECO:0000269|PubMed:9188622}.
CC -!- SUBUNIT: [Isoform M]: Associates with host chaperone CANX through its
CC pre-S2 N glycan; this association may be essential for isoform M proper
CC secretion. {ECO:0000269|PubMed:9420286}.
CC -!- SUBUNIT: [Isoform S]: Interacts with isoform L (PubMed:31700077).
CC Interacts with the antigens of satellite virus HDV (HDVAgs); this
CC interaction is required for encapsidation of HDV genomic RNA
CC (PubMed:8289368). {ECO:0000269|PubMed:31700077,
CC ECO:0000269|PubMed:8289368}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04075}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=L; Synonyms=Large envelope protein, LHB, L-HBsAg;
CC IsoId=P03141-1; Sequence=Displayed;
CC Name=M; Synonyms=Middle envelope protein, MHB, M-HBsAg;
CC IsoId=P03141-2; Sequence=VSP_030415;
CC Name=S; Synonyms=Small envelope protein, SHB, S-HBsAg;
CC IsoId=P03141-3; Sequence=VSP_030414;
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.
CC {ECO:0000250|UniProtKB:P03138, ECO:0000255|HAMAP-Rule:MF_04075}.
CC -!- PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04075,
CC ECO:0000269|PubMed:11350599}.
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; X02763; CAA26539.1; -; Genomic_DNA.
DR EMBL; J02205; AAA45524.1; -; Genomic_RNA.
DR PIR; A03706; SAVLVD.
DR ABCD; P03141; 3 sequenced antibodies.
DR Proteomes; UP000008766; Genome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
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;
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..400
FT /note="Large envelope protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT /id="PRO_0000038087"
FT TOPO_DOM 2..253
FT /note="Intravirion; in internal conformation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TOPO_DOM 2..181
FT /note="Virion surface; in external conformation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TRANSMEM 182..202
FT /note="Helical; Name=TM1; Note=In external conformation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TOPO_DOM 203..253
FT /note="Intravirion; in external conformation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TRANSMEM 254..274
FT /note="Helical; Name=TM2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TOPO_DOM 275..348
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TOPO_DOM 370..375
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TRANSMEM 376..398
FT /note="Helical; Name=TM3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT TOPO_DOM 399..400
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..174
FT /note="Pre-S"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT REGION 2..119
FT /note="Pre-S1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT REGION 89..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 120..174
FT /note="Pre-S2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT COMPBIAS 89..108
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 320
FT /note="N-linked (GlcNAc...) asparagine; by host; partial"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04075"
FT VAR_SEQ 1..174
FT /note="Missing (in isoform S)"
FT /evidence="ECO:0000305"
FT /id="VSP_030414"
FT VAR_SEQ 1..119
FT /note="Missing (in isoform M)"
FT /evidence="ECO:0000305"
FT /id="VSP_030415"
FT MOD_RES P03141-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000305"
FT CARBOHYD P03141-2:4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 400 AA; 43705 MW; 57356B6293872BC5 CRC64;
MGGWSSKPRK GMGTNLSVPN PLGFFPDHQL DPAFGANSNN PDWDFNPVKD DWPAANQVGV
GAFGPRLTPP HGGILGWSPQ AQGILTTVST IPPPASTNRQ SGRQPTPISP PLRDSHPQAM
QWNSTAFHQT LQDPRVRGLY LPAGGSSSGT VNPAPNIASH ISSISARTGD PVTNMENITS
GFLGPLLVLQ AGFFLLTRIL TIPQSLDSWW TSLNFLGGSP VCLGQNSQSP TSNHSPTSCP
PICPGYRWMC LRRFIIFLFI LLLCLIFLLV LLDYQGMLPV CPLIPGSTTT STGPCKTCTT
PAQGNSMFPS CCCTKPTDGN CTCIPIPSSW AFAKYLWEWA SVRFSWLSLL VPFVQWFVGL
SPTVWLSAIW MMWYWGPSLY SIVSPFIPLL PIFFCLWVYI
