UBE4A: Ubiquitination Factor E4A
A key component of the ubiquitin-proteasome system involved in protein degradation and neurodegenerative disorders.
Gene Information Card
| Symbol | UBE4A |
|---|---|
| Full Name | Ubiquitination Factor E4A |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 9354 ncbi.nlm.nih.gov/gene/9354 |
| Ensembl ID | ENSG00000110344 |
| UniProt ID | Q14139 |
| OMIM ID | 603753 |
| HGNC ID | 12499 |
| Aliases | UFD2, UBE4A_HUMAN |
Description
UBE4A encodes a ubiquitin conjugation factor E4 that functions as a ubiquitin chain elongation factor in the ubiquitin-proteasome system. It interacts with E1, E2, and E3 enzymes to add ubiquitin moieties to growing polyubiquitin chains, targeting proteins for proteasomal degradation. UBE4A is implicated in protein quality control and has been linked to neurodegenerative diseases such as spinocerebellar ataxia and Alzheimer's disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia (SCA) | UBE4A mutations impair ubiquitin chain elongation, leading to accumulation of misfolded proteins and neuronal toxicity. | ClinVar, OMIM |
| Alzheimer's disease | Altered UBE4A expression may disrupt tau and amyloid-beta clearance via the ubiquitin-proteasome pathway. | NCBI Gene, PubMed |
| Neurodevelopmental disorders | Loss-of-function variants in UBE4A are associated with intellectual disability and developmental delay. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Moderate expression |
| SH-SY5Y | 14.3 | High expression (neuronal) |
| HeLa | 7.8 | Low expression |
| HepG2 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1282C>T (p.Arg428*) | Nonsense | <0.01% | Loss of function; truncation of UBE4A protein |
| c.1015G>A (p.Gly339Arg) | Missense | <0.01% | Impaired ubiquitin chain elongation activity |
| c.1543_1544del (p.Leu515fs) | Frameshift | <0.01% | Loss of function; predicted protein truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent UBE4A protein, reducing ubiquitin chain elongation and proteasomal degradation.
Gain of Function (GOF)
No evidence of gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly339Arg) may act in a dominant-negative manner by interfering with wild-type UBE4A function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
UBE4A is a 130 kDa protein containing a U-box domain that mediates E4 ubiquitin chain elongation activity. It binds to ubiquitin-conjugated substrates and facilitates the addition of multiple ubiquitin molecules, promoting efficient proteasomal targeting. The protein is widely expressed, with highest levels in brain and testis. Structural studies indicate that the U-box domain is essential for interaction with E2 enzymes and for polyubiquitin chain assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBE4A Knockout HEK293 Cell Line | EDJ-KQ2756 | Human | 9354 | Details Get a Quote |
| UBE4A Knockout A-549 Cell Line | EDJ-KQ22282 | Human | 9354 | Details Get a Quote |
| UBE4A Knockout HCT 116 Cell Line | EDJ-KQ23653 | Human | 9354 | Details Get a Quote |
| UBE4A Knockout HeLa Cell Line | EDJ-KQ23654 | Human | 9354 | Details Get a Quote |
