UBE3A

This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

UBE3A

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 (PubMed:10373495, PubMed:16772533, PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24273172, PubMed:24728990).
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 (PubMed:10373495, PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24728990).
Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins (PubMed:19233847).
Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation (PubMed:24728990).
Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation (PubMed:16772533).
Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (By similarity).
Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533).
(Microbial infection) Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses.

Biological Process androgen receptor signaling pathway Source:Ensembl
Biological Process brain development Source:ProtInc1 Publication
Biological Process modulation of chemical synaptic transmission Source:Ensembl
Biological Process ovarian follicle development Source:Ensembl
Biological Process positive regulation of Golgi lumen acidification Source:Ensembl
Biological Process positive regulation of phosphatidylinositol 3-kinase signaling Source:Ensembl
Biological Process positive regulation of protein ubiquitination Source:CACAO1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:Ensembl
Biological Process progesterone receptor signaling pathway Source:UniProtKB1 Publication
Biological Process prostate gland growth Source:Ensembl
Biological Process protein autoubiquitination Source:FlyBase1 Publication
Biological Process protein K48-linked ubiquitination Source:UniProtKB1 Publication
Biological Process protein polyubiquitination Source:GO_Central1 Publication
Biological Process proteolysis Source:ProtInc1 Publication
Biological Process regulation of circadian rhythm Source:UniProtKB1 Publication
Biological Process regulation of ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process response to progesterone Source:UniProtKB1 Publication
Biological Process rhythmic process Source:UniProtKB-KW
Biological Process sperm entry Source:Ensembl
Biological Process ubiquitin-dependent protein catabolic process Source:ProtInc1 Publication

Cytoplasm
Nucleus

Angelman syndrome (AS):
A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue.

A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue.