UBE3A
Ubiquitin Protein Ligase E3A (Angelman Syndrome Gene)
Gene Information Card
| Symbol | UBE3A |
|---|---|
| Full Name | Ubiquitin Protein Ligase E3A |
| Gene Type | Protein coding |
| Chromosomal Location | 15q11.2 |
| NCBI Gene ID | 7337 ncbi.nlm.nih.gov/gene/7337 |
| Ensembl ID | ENSG00000114062 |
| UniProt ID | Q05086 |
| OMIM ID | 601623 |
| HGNC ID | 12496 |
| Aliases | E6-AP, EPVE6AP, HPVE6A |
Description
UBE3A encodes E6-associated protein (E6-AP), a HECT domain E3 ubiquitin ligase that targets proteins for proteasomal degradation. It is subject to genomic imprinting in neurons, with maternal allele expression predominant. Loss of maternal UBE3A function causes Angelman syndrome, a severe neurodevelopmental disorder. UBE3A also mediates p53 degradation in HPV-infected cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Angelman Syndrome | Loss of maternal UBE3A expression leads to impaired ubiquitination of synaptic proteins (e.g., Arc, Ephexin5), disrupting dendritic spine development and synaptic plasticity. | OMIM #105830; ClinVar; multiple case-control studies |
| Autism Spectrum Disorder | Rare UBE3A duplications or gain-of-function variants may alter synaptic protein turnover, contributing to ASD risk. | OMIM #611936; GWAS and sequencing studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.1 | High |
| Cerebellum | 18.5 | High |
| Cerebral cortex | 22.3 | High |
| Heart | 5.2 | Medium |
| Liver | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.4 | Neuronal model |
| HEK293 (embryonic kidney) | 8.7 | Common expression system |
| HeLa (cervical carcinoma) | 6.3 | HPV-positive line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1906C>T (p.Gln636*) | Nonsense | <0.01% in general population | Truncation; loss of HECT domain; Angelman syndrome |
| c.1312G>A (p.Glu438Lys) | Missense | Rare | Impaired ubiquitin transfer; Angelman syndrome |
| 15q11.2-q13.1 deletion | Copy number loss | ~70% of Angelman cases | Loss of maternal UBE3A; most common cause |
Mutation functional classification
Loss of Function (LOF)
Maternal UBE3A loss-of-function (nonsense, frameshift, deletion) causes Angelman syndrome due to insufficient E3 ligase activity in neurons.
Gain of Function (GOF)
UBE3A duplications or hypermorphic missense variants are associated with autism spectrum disorder, likely due to excessive ubiquitination of synaptic targets.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with wild-type UBE3A dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein ubiquitination |
| • proteasome-mediated ubiquitin-dependent protein catabolic process | • synaptic plasticity |
| • dendritic spine development |
Pathways
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• p53 degradation by E6-AP (Reactome R-HSA-8951664)
• Angelman syndrome pathway (Reactome R-HSA-5619507)
Protein Summary
UBE3A (E6-AP) is a 100 kDa HECT domain E3 ubiquitin ligase. It catalyzes the transfer of ubiquitin from E2 enzymes to substrate lysines, targeting proteins for proteasomal degradation. In neurons, it regulates synaptic proteins such as Arc and Ephexin5. The protein also interacts with HPV E6 to promote p53 degradation, linking UBE3A to oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBE3A Knockout HEK293 Cell Line | EDC07600 | Human | 7337 | Details Get a Quote |
| UBE3A Knockout A-549 Cell Line | EDJ-KQ23017 | Human | 7337 | Details Get a Quote |
| UBE3A Knockout HeLa Cell Line | EDJ-KQ23018 | Human | 7337 | Details Get a Quote |
| UBE3A Knockout HCT 116 Cell Line | EDJ-KQ21668 | Human | 7337 | Details Get a Quote |
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