HBSAG_HBVD3
ID HBSAG_HBVD3 Reviewed; 389 AA.
AC P03138;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 111.
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 France/Tiollais/1979)
OS (HBV-D).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC hepatitis B virus genotype D.
OX NCBI_TaxID=490133;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=399327; DOI=10.1038/281646a0;
RA Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P.;
RT "Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned
RT in E. coli.";
RL Nature 281:646-650(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Latvia;
RX PubMed=3996597; DOI=10.1016/0014-5793(85)80771-7;
RA Bichko V., Pushko P., Dreilina D., Pumpen P., Gren E.Y.;
RT "Subtype ayw variant of hepatitis B virus. DNA primary structure
RT analysis.";
RL FEBS Lett. 185:208-212(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Latvia;
RX PubMed=6373205;
RA Kozlovskaia T.M., Pumpen P.P., Borisova G.P., Dishler A.V., Bychko V.V.;
RT "Synthesis of the full amino acid sequence of the surface antigen of the
RT hepatitis B virus in Escherichia coli.";
RL Dokl. Akad. Nauk SSSR 274:1250-1253(1984).
RN [4]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=3573147; DOI=10.1128/jvi.61.5.1672-1677.1987;
RA Persing D.H., Varmus H.E., Ganem D.;
RT "The preS1 protein of hepatitis B virus is acylated at its amino terminus
RT with myristic acid.";
RL J. Virol. 61:1672-1677(1987).
RN [5]
RP TRANSMEMBRANE TOPOLOGY.
RX PubMed=7835336; DOI=10.1002/j.1460-2075.1995.tb06998.x;
RA Prange R., Streeck R.E.;
RT "Novel transmembrane topology of the hepatitis B virus envelope proteins.";
RL EMBO J. 14:247-256(1995).
RN [6]
RP MUTAGENESIS OF GLY-2.
RX PubMed=7491754; DOI=10.1006/viro.1995.0002;
RA Gripon P., Le Seyec J., Rumin S., Guguen-Guillouzo C.;
RT "Myristylation of the hepatitis B virus large surface protein is essential
RT for viral infectivity.";
RL Virology 213:292-299(1995).
RN [7]
RP FUNCTION.
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 [8]
RP GLYCOSYLATION (ISOFORM M), AND ACETYLATION AT MET-1 (ISOFORM M).
RC STRAIN=Isolate clinical;
RX PubMed=10207016; DOI=10.1074/jbc.274.17.11945;
RA Schmitt S., Glebe D., Alving K., Tolle T.K., Linder M., Geyer H.,
RA Linder D., Peter-Katalinic J., Gerlich W.H., Geyer R.;
RT "Analysis of the pre-S2 N- and O-linked glycans of the M surface protein
RT from human hepatitis B virus.";
RL J. Biol. Chem. 274:11945-11957(1999).
RN [9]
RP GLYCOSYLATION AT THR-37 (ISOFORM M).
RX PubMed=15218190; DOI=10.1099/vir.0.79932-0;
RA Schmitt S., Glebe D., Tolle T.K., Lochnit G., Linder D., Geyer R.,
RA Gerlich W.H.;
RT "Structure of pre-S2 N- and O-linked glycans in surface proteins from
RT different genotypes of hepatitis B virus.";
RL J. Gen. Virol. 85:2045-2053(2004).
RN [10]
RP FUNCTION.
RX PubMed=17020942; DOI=10.1128/jvi.00621-06;
RA Blanchet M., Sureau C.;
RT "Analysis of the cytosolic domains of the hepatitis B virus envelope
RT proteins for their function in viral particle assembly and infectivity.";
RL J. Virol. 80:11935-11945(2006).
RN [11]
RP MUTAGENESIS OF LEU-11; GLY-12 AND 13-PHE-PHE-14.
RX PubMed=16557545; DOI=10.1002/hep.21112;
RA Engelke M., Mills K., Seitz S., Simon P., Gripon P., Schnolzer M.,
RA Urban S.;
RT "Characterization of a hepatitis B and hepatitis delta virus receptor
RT binding site.";
RL Hepatology 43:750-760(2006).
RN [12]
RP MUTAGENESIS OF 11-LEU--PRO-15; 16-ASP--ASP-20; 21-PRO--ALA-25;
RP 26-ASN--PRO-30; 31-ASP--ASN-35; 36-PRO--THR-40; 41-TRP--ASN-45;
RP 46-LYS--GLY-50; 51-ALA--GLY-55; 56-PHE--HIS-60; 61-GLY--GLY-65;
RP 66-TRP--ALA-70; 71-GLN--GLN-75; 76-THR--ASN-80; 81-PRO--SER-85;
RP 86-THR--SER-90; 91-GLY--THR-95; 96-PRO--PRO-100; 101-LEU--HIS-105 AND
RP 106-PRO--GLN-110.
RX PubMed=17376925; DOI=10.1128/jvi.00096-07;
RA Blanchet M., Sureau C.;
RT "Infectivity determinants of the hepatitis B virus pre-S domain are
RT confined to the N-terminal 75 amino acid residues.";
RL J. Virol. 81:5841-5849(2007).
RN [13]
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 [14]
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 [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).
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. Interacts with host
CC chaperone CANX. {ECO:0000250|UniProtKB:P03141}.
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:0000250|UniProtKB:P03141}.
CC -!- SUBUNIT: [Isoform S]: Interacts with isoform L. Interacts with the
CC antigens of satellite virus HDV (HDVAgs); this interaction is required
CC for encapsidation of HDV genomic RNA. {ECO:0000250|UniProtKB:P03141}.
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=P03138-1; Sequence=Displayed;
CC Name=M; Synonyms=Middle envelope protein, MHB, M-HBsAg;
CC IsoId=P03138-2; Sequence=VSP_031405;
CC Name=S; Synonyms=Small envelope protein, SHB, S-HBsAg;
CC IsoId=P03138-3; Sequence=VSP_031404;
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, ECO:0000269|PubMed:10207016,
CC ECO:0000269|PubMed:15218190}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA45496.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA26324.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; V01460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X02496; CAA26324.1; ALT_INIT; Genomic_DNA.
DR EMBL; M12393; AAA45496.1; ALT_INIT; Genomic_DNA.
DR PIR; A03703; SAVLAH.
DR ELM; P03138; -.
DR BindingDB; P03138; -.
DR ABCD; P03138; 4 sequenced antibodies.
DR EvolutionaryTrace; P03138; -.
DR Proteomes; UP000007930; 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;
KW Reference proteome; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral penetration into host cytoplasm;
KW Virion; Virus endocytosis by host; 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_0000038107"
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 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 76..103
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 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_031404"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform M)"
FT /evidence="ECO:0000305"
FT /id="VSP_031405"
FT VARIANT 75
FT /note="Q -> E (in strain: Latvia)"
FT VARIANT 147
FT /note="A -> S (in strain: Latvia)"
FT VARIANT 150
FT /note="L -> I (in strain: Latvia)"
FT VARIANT 288..290
FT /note="MTT -> TTP (in strain: Latvia)"
FT MUTAGEN 2
FT /note="G->A: Complete loss of myristoylation. Complete loss
FT of infectivity."
FT /evidence="ECO:0000269|PubMed:7491754"
FT MUTAGEN 11..15
FT /note="LGFFP->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 11
FT /note="L->R: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:16557545"
FT MUTAGEN 12
FT /note="G->E: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:16557545"
FT MUTAGEN 13..14
FT /note="FF->SS: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:16557545"
FT MUTAGEN 13
FT /note="F->S: Complete loss of infectivity."
FT MUTAGEN 16..20
FT /note="DHQLD->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 21..25
FT /note="PAFRA->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 26..30
FT /note="NTANP->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 31..35
FT /note="DWDFN->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 36..40
FT /note="PNKDT->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 41..45
FT /note="WPDAN->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 47..50
FT /note="VGAG->L: Complete loss of infectivity."
FT MUTAGEN 51..55
FT /note="AFGLG->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 56..60
FT /note="FTPPH->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 61..65
FT /note="GGLLG->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 66..70
FT /note="WSPQA->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 71..75
FT /note="QGILQ->KL: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 76..80
FT /note="TLPAN->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 81..85
FT /note="PPPAS->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 86..90
FT /note="TNRQS->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 91..95
FT /note="GRQPT->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 96..100
FT /note="PLSPP->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 101..105
FT /note="LRNTH->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MUTAGEN 106..110
FT /note="PQAMQ->KL: No effect on infectivity."
FT /evidence="ECO:0000269|PubMed:17376925"
FT MOD_RES P03138-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:10207016"
FT CARBOHYD P03138-2:37
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:15218190"
SQ SEQUENCE 389 AA; 42766 MW; 6DC9E682DA694F63 CRC64;
MGQNLSTSNP LGFFPDHQLD PAFRANTANP DWDFNPNKDT WPDANKVGAG AFGLGFTPPH
GGLLGWSPQA QGILQTLPAN PPPASTNRQS GRQPTPLSPP LRNTHPQAMQ WNSTTFHQTL
QDPRVRGLYF PAGGSSSGTV NPVLTTASPL SSIFSRIGDP ALNMENITSG FLGPLLVLQA
GFFLLTRILT IPQSLDSWWT SLNFLGGTTV CLGQNSQSPT SNHSPTSCPP TCPGYRWMCL
RRFIIFLFIL LLCLIFLLVL LDYQGMLPVC PLIPGSSTTS TGPCRTCMTT AQGTSMYPSC
CCTKPSDGNC TCIPIPSSWA FGKFLWEWAS ARFSWLSLLV PFVQWFVGLS PTVWLSVIWM
MWYWGPSLYS ILSPFLPLLP IFFCLWVYI
