UBE3A

Chr 15q11.2

ubiquitin protein ligase E3A

Aliases:: AS, ANCR, E6-AP, FLJ26981
MANE:: ENST00000648336.2

OMIM: 601623 ↗NCBI: 7337 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

UBE3A · Q05086

v62025-08-01

Predicted Aligned Error matrix for UBE3A — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.8/ 100

Confident

875 residues

Confidence breakdown

Very high(≥ 90)51%
Confident(70–90)30%
Low(50–70)4%
Very low(< 50)14%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Severe microcephaly
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Disease associations (Open Targets)

Angelman syndrome
0.84
hereditary disease
0.55
Intellectual disability
0.51
neurodevelopmental disorder
0.35
Epileptic encephalopathy
0.34
Global developmental delay
0.34
Seizure
0.33
Abnormal corpus callosum morphology
0.33
Expressive language delay
0.33
Poor speech
0.33

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Ubiquitin-protein ligase E3A

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, PubMed:30020076). Several substrates have been identified including the BMAL1, ARC, LAMTOR1, 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, PubMed:30020076). 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). Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (By similarity). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533)