Tbio UBE3A Ubiquitin-protein ligase E3A

Protein Summary

Description

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 ARNTL/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 ARNTL/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. 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]

Uniprot Accession IDs

• Q05086
• A8K8Z9
• P78355
• Q93066
• Q9UEP4
• Q9UEP5
• Q9UEP6
• Q9UEP7
• Q9UEP8
• Q9UEP9

Gene Name

• UBE3A

Ensembl ID

• ENST00000232165
• ENSP00000232165
• ENSG00000114062
• ENST00000397954
• ENSP00000381045
• ENST00000428984
• ENSP00000401265
• ENST00000438097
• ENSP00000411258
• ENST00000566215
• ENSP00000457771
• ENST00000614096
• ENSP00000481796
• ENST00000630424
• ENSP00000486349
• ENST00000637886
• ENSP00000490258
• ENST00000638011
• ENSP00000490111
• ENST00000638155
• ENSP00000490557
• ENST00000648336
• ENSP00000497572
• ENST00000649550
• ENSP00000497549
• ENST00000650110
• ENSP00000497594

Symbol

• E6AP
• EPVE6AP
• HPVE6A
• AS
• ANCR
• E6-AP
• HPVE6A
• EPVE6AP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
kinase perturbation	1
viral protein	1
virus	1
transcription factor perturbation	0.97

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 802   (req: < 5)

Gene RIFs: 178   (req: <= 3)

Antibodies: 352   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 802   (req: >= 5)

Gene RIFs: 178   (req: > 3)

Antibodies: 352   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0