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-MAR-2008, entry version 32. DE Large envelope protein (Large surface protein) (L glycoprotein) (Major DE surface antigen) (Large S protein) (L-HBsAg) (LHB). GN Name=S; OS Hepatitis B virus genotype B2 (isolate Vietnam/16091/1992) (HBV-B). OC Viruses; Retro-transcribing viruses; Hepadnaviridae; OC 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 MEDLINE=20109034; PubMed=10640544; 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; 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; 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. It also assume fusion between CC virion membrane and cellular 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 (By similarity). 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 (By similarity). 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 (By similarity). CC -!- SUBCELLULAR LOCATION: Virion membrane (By similarity). 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 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. CC -!- PTM: Isoform M is N-terminaly acetylated at a ratio of 90%, and N- CC glycosylated at the pre-S2 region (By similarity). CC -!- PTM: Myristoylated (By similarity). 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. CC -!- WEB RESOURCE: Name=HepSEQ; Note=Hepatitis virus B database; CC URL="http://www.hpa-bioinfodatabases.org.uk/hepatitis_open/main.php"; 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 GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR InterPro; IPR000349; Hepvir_surfAg. DR Pfam; PF00695; vMSA; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative initiation; Alternative splicing; KW Glycoprotein; Lipoprotein; Membrane; Myristate; Transmembrane; Virion. FT INIT_MET 1 1 Removed; by host (By similarity). FT CHAIN 2 400 Large envelope protein. FT /FTId=PRO_0000319076. FT TOPO_DOM 2 253 Cytoplasmic; in internal conformation FT (Potential). FT TOPO_DOM 2 181 Extracellular; in external conformation FT (Potential). FT TRANSMEM 182 202 In external conformation (Potential). FT TOPO_DOM 203 253 Cytoplasmic; in external conformation FT (Potential). FT TRANSMEM 254 274 Potential. FT TOPO_DOM 275 348 Extracellular (Potential). FT TRANSMEM 349 369 Potential. FT TOPO_DOM 370 375 Cytoplasmic (Potential). FT TRANSMEM 376 398 Potential. FT TOPO_DOM 399 400 Extracellular (Potential). FT REGION 2 174 Pre-S. FT REGION 2 119 Pre-S1. FT REGION 120 174 Pre-S2. FT MOD_RES 120 120 N-acetylmethionine; by host; in isoform M FT (By similarity). FT LIPID 2 2 N-myristoyl glycine; by host (By FT similarity). FT CARBOHYD 123 123 N-linked (GlcNAc...); in isoform M (By FT similarity). FT CARBOHYD 320 320 N-linked (GlcNAc...) (By similarity). FT VAR_SEQ 1 174 Missing (in isoform S). FT /FTId=VSP_031375. FT VAR_SEQ 1 119 Missing (in isoform M). 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 //