ID HBSAG_HBVB5 Reviewed; 400 AA. AC Q9PWW3; Q9PX15; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 22-FEB-2023, entry version 77. 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 B2 (isolate Vietnam/16091/1992) (HBV-B). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Blubervirales; Hepadnaviridae; Orthohepadnavirus. OX NCBI_TaxID=489462; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=HBV/14611, HBV/16091, and HBV/IK29902; RX PubMed=10640544; DOI=10.1099/0022-1317-81-1-75; RA Hannoun C., Horal P., Lindh M.; RT "Long-term mutation rates in the hepatitis B virus genome."; RL J. Gen. Virol. 81:75-83(2000). 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: [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=Q9PWW3-1; Sequence=Displayed; CC Name=M; Synonyms=Middle envelope protein, MHB, M-HBsAg; CC IsoId=Q9PWW3-2; Sequence=VSP_031376; CC Name=S; Synonyms=Small envelope protein, SHB, S-HBsAg; CC IsoId=Q9PWW3-3; Sequence=VSP_031375; 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 -!- 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=AAF24688.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAF24702.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAF24709.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF121243; AAF24687.1; -; Genomic_DNA. DR EMBL; AF121243; AAF24688.1; ALT_INIT; Genomic_DNA. DR EMBL; AF121245; AAF24701.1; -; Genomic_DNA. DR EMBL; AF121245; AAF24702.1; ALT_INIT; Genomic_DNA. DR EMBL; AF121246; AAF24708.1; -; Genomic_DNA. DR EMBL; AF121246; AAF24709.1; ALT_INIT; Genomic_DNA. DR PIR; JQ2059; JQ2059. DR PIR; JQ2060; JQ2060. DR PIR; JQ2062; JQ2062. DR GlyCosmos; Q9PWW3; 2 sites, No reported glycans. DR Proteomes; UP000001386; Genome. DR Proteomes; UP000158684; Genome. DR Proteomes; UP000168764; Genome. DR GO; GO:0016020; C:membrane; 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; 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_0000319076" 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..51 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 85..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 85..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_031375" FT VAR_SEQ 1..119 FT /note="Missing (in isoform M)" FT /evidence="ECO:0000305" FT /id="VSP_031376" FT MOD_RES Q9PWW3-2:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000305" FT CARBOHYD Q9PWW3-2:4 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" SQ SEQUENCE 400 AA; 43751 MW; CE6F6A9093879343 CRC64; MGGWSSKPRK GMGTNLSVPN PLGFFPDHQL DPAFKANSEN PDWDLNPHKD NWPDANKVGV GAFGPGFTPP HGGLLGWSPQ AQGLLTTVPA APPPASTNRQ SGRQPTPLSP PLRDTHPQAM QWNSTTFHQT LQDPRVRALY FPAGGSSSGT VSPAQNTVST ISSILSKTGD PVPNMENIAS GLLGPLLVLQ AGFFLLTKIL TIPQSLDSWW TSLNFLGGTP VCLGQNSQSQ ISSHSPTCCP PICPGYRWMC LRRFIIFLCI LLLCLIFLLV LLDYQGMLPV CPLIPGSSTT STGPCKTCTT PAQGTSMFPS CCCTKPTDGN CTCIPIPSSW AFAKYLWEWA SVRFSWLSLL VPFVQWFVGL SPTVWLSVIW MMWFWGPSLY NILSPFMPLL PIFFCLWVYI //