This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. May induce fusion through binding of SLC1A4 and SLC1A5 (PubMed:10708449, PubMed:12050356, PubMed:23492904). Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes. The mature envelope protein (Env) consists of a trimer of SU-TM heterodimers attached probably by a labile interchain disulfide bond. Interacts with the C-type lectin CD209/DC-SIGN. 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 placental syncytiotrophoblast. Expressed at intermediate level in testis. Seems also to be found at low level in adrenal tissue, bone marrow, breast, colon, kidney, ovary, prostate, skin, spleen, thymus, thyroid, brain and trachea. Both mRNA and protein levels are significantly increased in the brain of individuals with multiple sclerosis, particularly in astrocytes and microglia. In placenta, detected at higher level during early pregnancy and at lower level during late pregnancy. The cytoplasmic region is essential for the fusiogenic function. The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo (By similarity). Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. The intracytoplasmic tail cleavage by the viral protease that is required for the fusiogenic activity of some retroviruses envelope proteins seems to have been lost during evolution. The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion. All variants have fusogenic properties. Probably involved in the development of multiple sclerosis (MS). MS is a neurodegenerative disease characterized by the gradual accumulation of focal plaques of demyelination particularly in the periventricular areas of the brain. It leads to physical and cognitive disabilities. Viral particles or intracellular RNA of HERV-W family members have been detected in tissue from patients with multiple sclerosis or schizophrenia. Orthologs in P.troglodytes, G.gorilla, P.pygmaeus and H.moloch. It can make pseudotypes with HIV-1 virions and confer infectivity. Can also induce cellular resistance to spleen necrosis virus in vitro. HERV-W family subgenomic RNAs have been observed. This provirus is intergenic, the closest flanking genes being ODAG and PEX1. The human genome contains a high percentage of proviral-like elements, also called endogenous retroviruses (ERVs) that are the genomic traces of ancient infections of the germline by exogenous retroviruses. Although most of these elements are defective, some have conserved a functional envelope (env) gene, most probably diverted by the host for its benefit. Belongs to the gamma type-C retroviral envelope protein family. HERV class-I W env subfamily. A virus for life - Issue 50 of September 2004