ERVW-1

Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on chromosome 7 that has inactivating mutations in the gag and pol genes. This gene is the envelope glycoprotein gene which appears to have been selectively preserved. The gene's protein product is expressed in the placental syncytiotrophoblast and is involved in fusion of the cytotrophoblast cells to form the syncytial layer of the placenta. The protein has the characteristics of a typical retroviral envelope protein, including a furin cleavage site that separates the surface (SU) and transmembrane (TM) proteins which form a heterodimer. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Endogenous Retrovirus Group W Member 1, Envelope

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.

Anatomical structure morphogenesis Source: ProtInc
Myoblast fusion Source: MGI
Syncytium formation Source: UniProtKB
Syncytium formation by plasma membrane fusion Source: UniProtKB

Surface protein: Cell membrane. The surface protein is not anchored to the membrane, but localizes to the extracellular surface through its binding to TM.
Transmembrane protein: Cell membrane
Syncytin-1: Virion

Extracellular: 21-443
Helical: 444-464
Cytoplasmic: 465-538

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.