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Description

Ubiquitin-protein ligase E3A (UniProt: Q05086, also known as EC: 2.3.2.26, E6AP ubiquitin-protein ligase, HECT-type ubiquitin transferase E3A, Human papillomavirus E6-associated protein, Oncogenic protein-associated protein E6-AP, Renal carcinoma antigen NY-REN-54) is encoded by the UBE3A (also known as E6AP, EPVE6AP, HPVE6A) gene (Gene ID: 7337)in human. UBE3A is the E3 ubiquitin-protein ligase that 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 RAD23A and RAD23B, MCM7, annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. UBE3A catalyzes the high-risk human papilloma virus (HPV) E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. Phosphorylation at Tyr659 by ABL1 impairs E3 ligase activity and protects p53/TP53 from degradation in (HPV)-infected cells. UBE3A may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins and it also promotes its own degradation in vivo. It is reported to plays an important role in the regulation of the circadian clock by ubiquitinating the core clock component ARNTL/BMAL1 and leading to its proteasomal degradation. Three isoforms of UBE3A have been reported that are generated via alternative splicing. Mutations in UBE3A gene cause Angelman syndrome that is characterized by severe motor and intellectual retardation, ataxia, hypotonia, and frequent jerky limb movements.