Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution. This envelope protein has superantigenic properties. SU mediates receptor recognition. TM anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane (By similarity). The surface (SU) and transmembrane (TM) proteins form a heterodimer. SU and TM are attached by noncovalent interactions or by a labile interchain disulfide bond (By similarity). The surface protein is not anchored to the membrane, but localizes to the extracellular surface through its binding to TM. Expressed at higher level in the thymus. Expressed at lower level in peripheral blood lymphocytes. High expression in thymocytes. Neither expressed nor inducible in mature T-cells. Inducible in CD2 negative peripheral blood lymphocytes. Induced by type I interferons and by Epstein-Barr virus (EBV). Specific enzymatic cleavages in vivo yield the mature SU and TM proteins. This envelope gene is polymorphic with at least three different alleles (called HERV-K18.1, HERV-K18.2 and HERV-K18.3). A polymorphism introducing a premature stop codon in position 154 is present in allele HERV-K18.1 resulting in a truncated SU protein. The sequence shown is that of HERV-K18.2. Some positive evidence of genetic association found between allele HERV-K18.3 and type 1 diabetes. Orthologs in P.troglodytes and G.gorilla. Has a type 1 genome. The HERV-K(HML-2) family contains type 1 and type 2 genomes depending on the absence or presence of 292 nucleotides at the 5'-end of the env gene resulting in Env proteins of distinct sizes. Despite their overall retroviral envelope structure HERV-K(HML-2) type 1 envelope proteins lack a predictable signal sequence. Subgenomic RNA transcripts coding for full-length envelope proteins have been detected for both type of genomes. Autoantibodies reactive to this envelope are detectable in sera from healthy donors and individuals with autoimmune diseases. Intragenic, in the first intron of CD48 gene. Belongs to the beta type-B retroviral envelope protein family. HERV class-II K(HML-2) env subfamily. No predictable signal peptide.