Sperm-egg fusion protein TMEM95 (TMEM95)

Sperm-egg fusion protein TMEM95 (TMEM95) is a highly conserved, single-pass type I transmembrane protein localized on the sperm membrane, specifically at the acrosome and relocalizing to the equatorial segment after the acrosome reaction. TMEM95 is essential for male fertility in mammals: its absence causes complete male-specific sterility in mice, as sperm lacking TMEM95 retain normal morphology and motility, and can bind eggs, but are unable to undergo membrane fusion with the oolemma. TMEM95's structure reveals an N-terminal α-helical bundle and a C-terminal β-hairpin, with homology to the N-terminus of IZUMO1, but lacking IZUMO1’s C-terminal immunoglobulin-like domain. Human TMEM95 binds to receptor(s) on the egg membrane, and monoclonal antibodies against TMEM95 can block sperm-egg fusion without affecting sperm-egg binding, indicating TMEM95's direct, critical role in the membrane fusion step of fertilization. Loss-of-function mutations in TMEM95 have been linked to infertility in male mice and subfertility in cattle, without affecting sperm development or motility, highlighting its specific function in membrane fusion rather than in spermatogenesis or sperm transport. There is currently no evidence of direct drug targeting or biomarker utility for TMEM95, and it is principally relevant in the context of reproductive biology and infertility.

Other names

TMEM95UNQ9390/PRO34281MGC129793UNQ9390Transmembrane protein 95sperm-egg fusion protein TMEM95