E3 ubiquitin-protein ligase PHF7 (PHF7)

E3 ubiquitin-protein ligase PHF7 (PHF7) is a multidomain protein containing extended plant homeodomain (ePHD) and RING finger domains, acting as a RING-type E3 ubiquitin ligase. PHF7 is specifically and predominantly expressed in the male germline, where it is essential for proper progression of spermatogenesis and male fertility. PHF7's domains cooperate for substrate recognition and catalytic activity: the ePHD recognizes nucleosomal DNA, while its PHD domain binds to methylated lysine 4 of histone H3 (H3K4me2/3), acting as an epigenetic reader, and the RING domain confers E3 ubiquitin ligase activity, specifically targeting lysine 14 of histone H3 and histone H2A for ubiquitination. These modifications facilitate the critical histone-to-protamine exchange necessary for maturation of elongating spermatids. Loss of PHF7 impairs histone removal, resulting in male infertility due to defective chromatin remodeling. PHF7 additionally appears to promote and induce male germline identity and is involved in epigenetic regulation by coordinating histone binding and ubiquitination[1][2][3][4][5]. There are currently no drugs or clinical biomarkers linked to PHF7; its role is of scientific interest as a fundamental regulator of spermatogenesis and epigenetic reprogramming, but it is not considered a therapeutic target in current literature.

Other names

PHF7PHD finger protein 7E3 ubiquitin-protein ligase PHF7NYD-SP6HSPC226HSPC045testicular secretory protein Li 34testis development protein NYD-SP6