UBE3A (ubiquitin-protein ligase E3A, AKA E6AP) is an E3 ubiquitin-protein ligase 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 ARNTL/BMAL1, ARC, RAD23A, RAD23B, MCM7, annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, UBE3A may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. UBE3A also plays an important role in the regulation of the circadian clock. Defects in UBE3A are a cause of Angelman syndrome (AS).