HBSAG_HBVA8
ID HBSAG_HBVA8 Reviewed; 400 AA.
AC Q4R1S6;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 23-FEB-2022, entry version 56.
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 A3 (isolate Cameroon/CMR983/1994) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=489458;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15958684; DOI=10.1099/vir.0.80922-0;
RA Kurbanov F., Tanaka Y., Fujiwara K., Sugauchi F., Mbanya D., Zekeng L.,
RA Ndembi N., Ngansop C., Kaptue L., Miura T., Ido E., Hayami M., Ichimura H.,
RA Mizokami M.;
RT "A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination
RT between genotypes A and E in Cameroon.";
RL J. Gen. Virol. 86:2047-2056(2005).
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=Q4R1S6-1; Sequence=Displayed;
CC Name=S; Synonyms=Small envelope protein, SHB, S-HBsAg;
CC IsoId=Q4R1S6-2; Sequence=VSP_031364;
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; AB194950; BAE00090.1; -; Genomic_DNA.
DR Proteomes; UP000007911; 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_0000319073"
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 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 84..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 84..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"
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_031364"
SQ SEQUENCE 400 AA; 43771 MW; 22EFBE19CF481468 CRC64;
MGGWLPKPRK GMGTNLSVPN PLGFFPDHQL DPAFGANSNN PDWDFNPIKD HWPQANQVGV
GAFGPGFTPP HGGVLGWSPQ AQGTLTTVPA VPPPASANRQ SGRQPTPISP PLRDSHPQAI
KWNSPAFHQA LQDPRVKGLY FPAGGSSSGT VSPVPNIASH ISSISSRTGD PAPTMENITS
GFLGPLLVLQ AGFFLLTRIL TIPQSLDSWW TSLNFLGGSP VCLGQNSQSP TSNHSPTSCP
PICPGYRWMC LRRFIIFLFI LLLCLIFLLV LLDYQGMLPV CPLIPGSTTT STGPCRTCTT
PAQGNSMFPS CCCTKPTDGN CTCIPIPSSW AFAKYLWEWA SVRFSWLSLL VPFVQWFVGL
SPTVWLSVIW MMWYWGPRLY NILSPFIPLL PIFFCLWVYI
