The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein. The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid. In its internal form (Li-HBsAg), interacts with the capsid protein and with the isoform S. Interacts with host chaperone CANX. Associates with host chaperone CANX through its pre-S2 N glycan; this association may be essential for isoform M proper secretion. Interacts with isoform L. Interacts with the antigens of satellite virus HDV (HDVAgs); this interaction is required for encapsidation of HDV genomic RNA. The large envelope protein is synthesized with the pre-S region at the cytosolic side of the endoplasmic reticulum and, hence will be within the virion after budding. Therefore the pre-S region is not N-glycosylated. Later a post-translational translocation of N-terminal pre-S and TM1 domains occur in about 50% of proteins at the virion surface. These molecules change their topology by an unknown mechanism, resulting in exposure of pre-S region at virion surface. For isoform M in contrast, the pre-S2 region is translocated cotranslationally to the endoplasmic reticulum lumen and is N-glycosylated. Isoform M is N-terminally acetylated by host at a ratio of 90%, and N-glycosylated by host at the pre-S2 region. Myristoylated. Belongs to the orthohepadnavirus major surface antigen family.