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 18-SEP-2019, entry version 70. 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; 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 RT particle 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 CC other 'internal' or Li-HBsAg. In its external conformation the CC protein attaches the virus to cell receptors and thereby CC initiating infection. This interaction determines the species CC specificity and liver tropism. This attachment induces virion CC internalization predominantly through caveolin-mediated CC endocytosis. The large envelope protein also assures fusion CC 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 CC the budding of the virion. It is involved in the induction of CC budding in a nucleocapsid independent way. In this process the CC majority of envelope proteins bud to form subviral lipoprotein CC particles of 22 nm of diameter that do not contain a nucleocapsid. CC {ECO:0000255|HAMAP-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 CC through its pre-S2 N glycan. This association may be essential for CC M proper 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=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 Note=Contains a N-acetylmethionine at position 1. Contains a CC N-linked (GlcNAc...) asparagine at position 4. CC {ECO:0000250|UniProtKB:P03138}; 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 CC region at the cytosolic side of the endoplasmic reticulum and, CC hence will be within the virion after budding. Therefore the pre-S CC region is not N-glycosylated. Later a post-translational CC translocation of N-terminal pre-S and TM1 domains occur in about CC 50% of proteins at the virion surface. These molecules change CC their topology by an unknown mechanism, resulting in exposure of CC pre-S region at virion surface. For isoform M in contrast, the CC pre-S2 region is translocated cotranslationally to the endoplasmic CC 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 CC 90%, 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 CC hepatitis B virus carriers. The vaccine is now produced by CC recombinant DNA techniques and expression of the S isoform in CC yeast cells. The pre-S region do not seem to induce strong enough CC 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 SMR; Q9PWW3; -. DR Proteomes; UP000001386; Genome. DR Proteomes; UP000158684; Genome. DR Proteomes; UP000168764; 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; Complete proteome; 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 Transmembrane; Transmembrane helix; Viral attachment to host cell; KW Viral penetration into host cytoplasm; Virion; KW Virus endocytosis by host; Virus entry into host cell. FT INIT_MET 1 1 Removed; by host. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT CHAIN 2 400 Large envelope protein. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT /FTId=PRO_0000319076. FT TOPO_DOM 2 253 Intravirion; in internal conformation. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT TOPO_DOM 2 181 Virion surface; in external conformation. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT TRANSMEM 182 202 Helical; Name=TM1; Note=In external FT conformation. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TOPO_DOM 203 253 Intravirion; in external conformation. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT TRANSMEM 254 274 Helical; Name=TM2. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TOPO_DOM 275 348 Virion surface. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TRANSMEM 349 369 Helical. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TOPO_DOM 370 375 Intravirion. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TRANSMEM 376 398 Helical; Name=TM3. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT TOPO_DOM 399 400 Virion surface. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT REGION 2 174 Pre-S. {ECO:0000255|HAMAP-Rule:MF_04075}. FT REGION 2 119 Pre-S1. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT REGION 120 174 Pre-S2. {ECO:0000255|HAMAP- FT Rule:MF_04075}. FT LIPID 2 2 N-myristoyl glycine; by host. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT CARBOHYD 320 320 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255|HAMAP-Rule:MF_04075}. FT VAR_SEQ 1 174 Missing (in isoform S). {ECO:0000305}. FT /FTId=VSP_031375. FT VAR_SEQ 1 119 Missing (in isoform M). {ECO:0000305}. FT /FTId=VSP_031376. 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 //