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Angelman syndrome (AS) , characterized by microcephaly, seizures, motor dysfunction, and mental retardation, is a result of maternal chromosome deletions in the region 15q11-q13 associated with ubiquitin-protein ligase E3A (UBE3A) critical region [379] Angelman syndrome (AS) UBE3A encodes E6-associated protein (E6-AP), which acts as a cellular ubiquitin ligase and establishes a covalent linkage between a 76-amino acid ubiquitin molecule and its target protein to form a polyubiquitylated substrate [379]