E3 ubiquitin-protein ligase (UBE3A) which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the BMAL1, ARC, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo. It Plays an important role in the regulation of the circadian clock, leading to its proteasomal degradation. UBE3A acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation and as a regulator of synaptic development by mediating ubiquitination and degradation of ARC.
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