UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4

UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>UBR4</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Ubiquitin Protein Ligase E3 Component N-Recognin 4</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p36.21</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/54716" target="_blank">54716</a></td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Retina, Peripheral tissues</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4

Introduction

UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>UBR4</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Ubiquitin Protein Ligase E3 Component N-Recognin 4</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p36.21</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/54716" target="_blank">54716</a></td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Retina, Peripheral tissues</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

UBR4 — Ubiquitin Protein Ligase E3 Component N-Recognin 4

Introduction

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. [@kanelis2010]

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.

Gene Structure and Basic Information

Genomic Organization

| Property | Value |
|----------|-------|
| Gene Symbol | UBR4 |
| Aliases | ZNF407, RNF127 |
| Chromosomal Location | 1p36.21 |
| NCBI Gene ID | 54716 |
| UniProt | Q6ZNA4 |

Protein Structure

UBR4 is a large protein (~500 kDa) containing:

• Multiple zinc finger domains
• UBR-type zinc finger motifs for substrate recognition
• RING finger domain for E3 ligase activity

Normal Biological Functions

N-End Rule Pathway

UBR4 functions in the N-end rule pathway:

This pathway regulates numerous cellular processes including:

• Stress response: Turnover of damaged proteins
• Signal transduction: Degradation of signaling components
• Development: Temporal protein regulation

Protein Quality Control

UBR4 contributes to neuronal protein quality control:

• Aggregate clearance: Targeting misfolded proteins
• Turnover regulation: Degradation of specific neuronal proteins
• Stress response: Mediates degradation under cellular stress

Disease Associations

Alzheimer's Disease

• APP processing: UBR4 may affect amyloid precursor protein metabolism
• Tau turnover: Involved in tau protein degradation
• Synaptic dysfunction: Altered UBR4 in AD brain

Parkinson's Disease

• α-Synuclein clearance: UBR4 may contribute to α-synuclein turnover
• Dopaminergic neuron survival: Required for neuronal protein homeostasis

ALS

• Protein aggregation: UBR4 dysfunction may contribute to inclusions
• Motor neuron vulnerability: Required for motor neuron health

Molecular Mechanisms

Substrate Specificity

UBR4 recognizes N-terminal residues:

• Basic: Arg, Lys, His
• Bulky hydrophobic: Leu, Phe, Tyr, Trp

Signaling Interactions

UBR4 interacts with:

• Components of the ubiquitin-proteasome system
• Molecular chaperones
• Signaling pathways

Therapeutic Implications

Drug Development

| Strategy | Target | Stage |
|----------|--------|-------|
| E3 ligase modulators | UBR4 activity | Discovery |
| N-end rule pathway | UBR4 substrates | Research |
| Gene therapy | UBR4 expression | Preclinical |

Pathway & Interaction Diagram

Interactive diagram showing UBR4's key relationships in the SciDEX knowledge graph (6 connections shown).

References

External Links

• [NCBI Gene: UBR4](https://www.ncbi.nlm.nih.gov/gene/54716)

See Also

• [Genes Index](/genes)
• [N-End Rule Pathway](/mechanisms/n-end-rule-pathway)
• [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)