UBR4: E3 Ubiquitin-Protein Ligase and Key Regulator of Proteostasis
A comprehensive resource on UBR4 gene, its protein product, associated diseases, expression, mutations, and functional roles.
Gene Information Card
| Symbol | UBR4 |
|---|---|
| Full Name | Ubiquitin Protein Ligase E3 Component N-Recognin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 23352 ncbi.nlm.nih.gov/gene/23352 |
| Ensembl ID | ENSG00000117481 |
| UniProt ID | Q5T4S7 |
| OMIM ID | 609890 |
| HGNC ID | 30313 |
| Aliases | KIAA0462, N-recognin-4, p600, UBR4 |
Description
UBR4 (Ubiquitin Protein Ligase E3 Component N-Recognin 4) encodes a 570 kDa protein that functions as an E3 ubiquitin-protein ligase in the N-end rule pathway. It recognizes N-terminal destabilizing residues of substrates and mediates their ubiquitination, targeting them for proteasomal degradation. UBR4 is involved in diverse cellular processes including proteostasis, cell cycle regulation, apoptosis, and cytoskeletal organization. It is also known as p600 and plays roles in integrin-mediated signaling and cell adhesion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | UBR4 mutations and altered expression may disrupt proteostasis and cell cycle control, contributing to tumorigenesis. | COSMIC; ClinVar |
| Neurodevelopmental disorders | Deleterious variants in UBR4 have been associated with intellectual disability and developmental delay. | ClinVar; OMIM |
| Alzheimer's disease | UBR4 interacts with tau and may influence tau aggregation and clearance. | NCBI Gene; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 12.8 | Medium |
| Kidney | 10.5 | Medium |
| Liver | 8.3 | Low |
| Heart | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 14.2 | Medium expression |
| K562 | 9.8 | Low expression |
| A549 | 11.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | 0.01% | Loss of function; premature stop codon |
| c.4567G>A (p.Glu1523Lys) | Missense | 0.03% | Unknown; possibly damaging |
| c.7890_7891insA (p.Leu2631Thrfs*5) | Frameshift | 0.005% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay.
Gain of Function (GOF)
Not well documented; some missense variants may alter substrate specificity.
Dominant Negative (DN)
Not reported for UBR4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• N-end rule pathway (R-HSA-983168)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
• Cell cycle (KEGG hsa04110)
Protein Summary
UBR4 is a large E3 ubiquitin-protein ligase (570 kDa) that acts as an N-recognin in the N-end rule pathway. It binds to N-terminal destabilizing residues of substrates and catalyzes their ubiquitination, targeting them for proteasomal degradation. The protein contains a UBR box, a zinc finger domain, and multiple WD40 repeats. It localizes to the cytoplasm and nucleus and interacts with proteins involved in cell adhesion, cytoskeletal dynamics, and apoptosis. UBR4 is essential for normal development and its dysregulation is linked to cancer and neurological disorders.
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