Frey regulator of sperm-oocyte fusion 1 (FREY1)

Frey regulator of sperm-oocyte fusion 1 (Frey1, FREY1, also known as C11orf94 or 1700029I15Rik) is a small, testis-specific type II transmembrane protein identified as the first endogenous inhibitor of the aspartic intramembrane-cleaving protease SPPL2c. Frey1 blocks SPPL2c-mediated proteolysis by a unique mechanism in which its transmembrane domain occupies the catalytic center, thereby preventing cleavage of physiological substrates. Structural studies have mapped crucial inhibitory motifs to specific residues within Frey1's transmembrane helix, mainly at the N-terminal region. This inhibition is selective for SPPL2c and does not extend to catalytically inactive SPPL2c mutants. While Frey1-mediated regulation of SPPL2c may have implications for protease-related signaling pathways and diseases such as Alzheimer’s disease, current data do not support its direct involvement as a therapeutic target or its interaction with any drugs[1][2].

Other names

Protein Frey 1C11orf94FREY1700029I15Rikuncharacterized protein C11orf94protein Frey

Acts as an endogenous protein inhibitor by blocking the catalytic site of SPPL2c through its transmembrane domain, preventing substrate access and proteolysis