WD repeat domain 20 (WDR20)

WD repeat domain 20 (WDR20) is a member of the WD repeat domain protein family characterized by several WD40 motifs that enable protein-protein interactions through a β-propeller structure[1][2]. WDR20 acts as a regulatory subunit that preserves and modulates the activity of the USP12-UAF1 deubiquitinating enzyme complex, which is involved in removing ubiquitin from target proteins and regulating their stability and localization[2]. WDR20 anchors USP12 at the base of its ubiquitin-contacting loop and allosterically influences the catalytic center, controlling the deubiquitination process. It shuttles the USP12 complex between the plasma membrane, cytoplasm, and nucleus[2]. Diseases associated with mutations in the WDR20 gene include Temple syndrome and Mulchandani-Bhoj-Conlin syndrome[2]. WDR20 does not have direct small molecule modulators currently known in clinical use or development, but its role as a scaffold and regulator of deubiquitinating complexes makes it of emerging interest in pathways relevant to cancer and protein homeostasis[2][3].

Other names

DMR

Modulation of deubiquitination via activation/regulation of USP12-UAF1 complexes