Ubiquitin-protein ligase E3C (UBE3C)

Ubiquitin-protein ligase E3C (UBE3C) is a member of the HECT family of E3 ubiquitin ligases, specifically of the 'other' HECT subfamily[1][3]. It catalyzes the formation of Lys29- and Lys48-linked polyubiquitin chains, targeting substrate proteins for proteasome-mediated degradation[6][2]. UBE3C enhances proteasome processivity, particularly facilitating the complete degradation of substrates that are otherwise recalcitrant or partially processed, thereby preventing the accumulation of harmful protein fragments[2]. It plays important biological roles in protein quality control, innate immunity, cellular stress responses, and is implicated in various disease processes, including cancer, where it may influence tumor progression and metastasis, and neurodevelopmental disorders, including autism spectrum disorder[1][2][3][6]. UBE3C also restricts certain viral infections by ubiquitinating viral proteins and promoting their degradation[5]. Structural studies reveal it has a classic HECT domain organization crucial for its activity and interactions with the proteasome[1][3][2]. Defects in UBE3C function can lead to impaired protein degradation and are associated with human disease.

Other names

KIAA0010KIAA10HectH2RAULHECTH2NDSMBANEDSMBARTA-associated ubiquitin ligasehomologous to E6AP carboxyl terminus homologous protein 2

Facilitates Lys29- and Lys48-linked polyubiquitin chain formation for substrate degradation; Promotes proteasomal degradation of partially unfolded, misfolded, or stable protein substrates; Ubiquitinates viral proteins (e.g., EV-A71 2C protein) to mediate antiviral responses