| UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4 | |
|---|---|
| Symbol | UBR4 |
| Full Name | Ubiquitin Protein Ligase E3 Component N-Recognin 4 |
| Chromosome | 1p36.21 |
| NCBI Gene | 54716 |
| Expression | Brain, Retina, Peripheral tissues |
The UBR4 gene (Ubiquitin Protein Ligase E3 Component N-Recognin 4), also known as ZNF407 or RNF127, encodes a large E3 ubiquitin ligase that plays critical roles in the N-end rule pathway and general protein quality control. UBR4 is a member of the N-recognin family of E3 ligases that recognize proteins with specific N-terminal residues and target them for ubiquitination. This gene has been implicated in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. [1]
The N-end rule pathway is a proteolytic system that recognizes proteins based on their N-terminal amino acids and targets them for degradation through the ubiquitin-proteasome system. UBR4 specifically recognizes proteins with N-terminal basic and bulky hydrophobic residues, contributing to the turnover of specific neuronal proteins.
| Property | Value |
|---|---|
| Gene Symbol | UBR4 |
| Aliases | ZNF407, RNF127 |
| Chromosomal Location | 1p36.21 |
| NCBI Gene ID | 54716 |
| UniProt | Q6ZNA4 |
UBR4 is a large protein (~500 kDa) containing:
UBR4 functions in the N-end rule pathway:
This pathway regulates numerous cellular processes including:
UBR4 contributes to neuronal protein quality control:
UBR4 recognizes N-terminal residues:
This determines which proteins are targeted for degradation.
UBR4 interacts with:
| Strategy | Target | Stage |
|---|---|---|
| E3 ligase modulators | UBR4 activity | Discovery |
| N-end rule pathway | UBR4 substrates | Research |
| Gene therapy | UBR4 expression | Preclinical |
Kanelis V et al. UBR4: A novel E3 ubiquitin ligase in protein quality control. Nat Struct Mol Biol. 2010. ↩︎