Protein: Q05086

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
Q05086 (Uniprot) UBE3A_HUMAN UBE3A Ubiquitin-protein ligase E3A human No
Uniprot: 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 RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. 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). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533). more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0007165 signal transduction 4 GO:0006139 nucleobase-containing compound metabolic process 480 1.10e-111 5.07e-25
GO:0009056 catabolic process 125 GO:0009059 macromolecule biosynthetic process 243 6.37e-04 1.88e-40
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
4 GO:0035556 intracellular signal transduction
4 GO:0031399 regulation of protein modification process
4 GO:0009966 regulation of signal transduction
123 GO:0006464 cellular protein modification process
123 GO:0006355 regulation of transcription, DNA-templated
125 GO:0044248 cellular catabolic process
125 GO:0016567 protein ubiquitination
125 GO:0060255 regulation of macromolecule metabolic process
172 GO:0060255 regulation of macromolecule metabolic process
243 GO:0034645 cellular macromolecule biosynthetic process
243 GO:0044271 cellular nitrogen compound biosynthetic process
243 GO:0006464 cellular protein modification process
243 GO:0031325 positive regulation of cellular metabolic process
243 GO:0010604 positive regulation of macromolecule metabolic process
243 GO:0051173 positive regulation of nitrogen compound metabolic process
243 GO:0051252 regulation of RNA metabolic process
243 GO:0031326 regulation of cellular biosynthetic process
243 GO:0032268 regulation of cellular protein metabolic process
243 GO:0010468 regulation of gene expression
243 GO:0010556 regulation of macromolecule biosynthetic process
243 GO:0007165 signal transduction
287 GO:0006464 cellular protein modification process
287 GO:0006355 regulation of transcription, DNA-templated
310 GO:0019538 protein metabolic process
480 GO:0034654 nucleobase-containing compound biosynthetic process
544 GO:0016070 RNA metabolic process
544 GO:0006464 cellular protein modification process
544 GO:0006796 phosphate-containing compound metabolic process
544 GO:0031325 positive regulation of cellular metabolic process
544 GO:0010604 positive regulation of macromolecule metabolic process
544 GO:0051173 positive regulation of nitrogen compound metabolic process
544 GO:0032268 regulation of cellular protein metabolic process
544 GO:0010468 regulation of gene expression
544 GO:0023051 regulation of signaling
544 GO:0007165 signal transduction
652 GO:0044267 cellular protein metabolic process
652 GO:0060255 regulation of macromolecule metabolic process
680 GO:0016070 RNA metabolic process
680 GO:0009059 macromolecule biosynthetic process
680 GO:0060255 regulation of macromolecule metabolic process
704 GO:0007165 signal transduction
775 GO:0044267 cellular protein metabolic process
775 GO:0010467 gene expression
775 GO:0006139 nucleobase-containing compound metabolic process
775 GO:0060255 regulation of macromolecule metabolic process
836 GO:0007165 signal transduction
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
4 GO:0005829 cytosol
4 GO:0005634 nucleus
123 GO:0043232 intracellular non-membrane-bounded organelle
123 GO:0005654 nucleoplasm
125 GO:0005829 cytosol
125 GO:0005634 nucleus
213 GO:0005634 nucleus
243 GO:0005829 cytosol
243 GO:0070013 intracellular organelle lumen
243 GO:0044428 nuclear part
287 GO:0005829 cytosol
287 GO:0043232 intracellular non-membrane-bounded organelle
287 GO:0031981 nuclear lumen
310 GO:0005829 cytosol
310 GO:0005634 nucleus
368 GO:0005829 cytosol
368 GO:0005634 nucleus
368 GO:0031982 vesicle
480 GO:0005654 nucleoplasm
544 GO:0005829 cytosol
544 GO:0005634 nucleus
652 GO:0005829 cytosol
652 GO:0005634 nucleus
652 GO:0031982 vesicle
680 GO:0005634 nucleus
775 GO:0005829 cytosol
775 GO:0005634 nucleus
836 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0001541 ovarian follicle development IEA
GO:0006508 proteolysis TAS
GO:0006511 ubiquitin-dependent protein catabolic process IEA
GO:0007420 brain development TAS
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling IEA
GO:0016032 viral process IEA
GO:0030521 androgen receptor signaling pathway IEA
GO:0031398 positive regulation of protein ubiquitination IDA
GO:0032570 response to progesterone IDA
GO:0035037 sperm entry IEA
GO:0042220 response to cocaine IEA
GO:0042542 response to hydrogen peroxide IEA
GO:0042752 regulation of circadian rhythm IMP
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IEA
GO:0050847 progesterone receptor signaling pathway IDA
GO:0051865 protein autoubiquitination IDA
GO:0060736 prostate gland growth IEA
GO:0061002 negative regulation of dendritic spine morphogenesis IEA
GO:0070936 protein K48-linked ubiquitination IDA
GO:1990416 cellular response to brain-derived neurotrophic factor stimulus IEA
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process IMP
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000502 proteasome complex IEA
GO:0005634 nucleus IEA
GO:0005737 cytoplasm IBA
GO:0005829 cytosol IEA
No pairs of PrOnto dissimilar CC GO terms found.
PMID Article Title
8380895 Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53.
8988171 UBE3A/E6-AP mutations cause Angelman syndrome.
8988172 De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome.
9143503 The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing.
9585605 Mutation analysis of UBE3A in Angelman syndrome patients.
9688277 The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate.
10373495 Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination.
10508479 Antigens recognized by autologous antibody in patients with renal-cell carcinoma.
10558980 Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.
10983987 The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome.
11170455 Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP.
12207887 VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
16572171 Analysis of the DNA sequence and duplication history of human chromosome 15.
16772533 WW domain binding protein-2, an E6-associated protein interacting protein, acts as a coactivator of estrogen and progesterone receptors.
17108031 E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein.
17323924 Mass spectrometric characterization of the affinity-purified human 26S proteasome complex.
17525332 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
19204938 Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation.
19233847 The ubiquitin ligase E6-AP is induced and recruited to aggresomes in response to proteasome inhibition and may be involved in the ubiquitination of Hsp70-bound misfolded proteins.
19325566 E6AP promotes the degradation of the PML tumor suppressor.
19591933 UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degrADation of p27.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
21269460 Initial characterization of the human central proteome.
21642474 Tyrosine phosphorylation of transcriptional coactivator WW-domain binding protein 2 regulates estrogen receptor alpha function in breast cancer via the Wnt pathway.
21947926 Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A.
22645313 Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes.
23581475 c-Abl phosphorylates E6AP and regulates its E3 ubiquitin ligase activity.
24273172 The active form of E6-associated protein (E6AP)/UBE3A ubiquitin ligase is an oligomer.
24728990 The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor.
25212744 Mutation update for UBE3A variants in Angelman syndrome.
OMIM ID Disease Name
105830 Angelman syndrome
Domain Name Domain ID Source
HECT_dom IPR000569 InterPro
UBE3A IPR017134 InterPro
AZUL IPR032353 InterPro
Hect_E3_ubiquitin_ligase IPR035983 InterPro
HECT PF00632 Pfam
AZUL PF16558 Pfam
Ubiquitin-protein_ligase_E6-AP PIRSF037201 PIRSF
HECT PS50237 PROSITE
HECTc SM00119 SMART
SSF56204 SSF56204 SUPFAM
HECTc cd00078 CDD