UBE2N Protein

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UBE2N Protein

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UBE2N Protein — Ubiquitin-Conjugating Enzyme E2 N

Introduction

Ube2N Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e65100; color:white; text-align:center; font-size:1.1em;">UBE2N Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Ubiquitin-Conjugating Enzyme E2 N (UEV1A)</td></tr>
<tr><td><strong>Gene</strong></td><td>[UBE2N](/genes/ube2n)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P61079](https://www.uniprot.org/uniprot/P61079)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>1XWH, 2GMI, 3H3Z</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>17 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, Nucleus</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Ubiquitin-conjugating enzyme family</td></tr>
<tr><td><strong>Aliases</strong></td><td>Ubc13, UEV1A, E2-25K</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>
</div>

Overview

...

UBE2N Protein — Ubiquitin-Conjugating Enzyme E2 N

Introduction

Ube2N Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e65100; color:white; text-align:center; font-size:1.1em;">UBE2N Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Ubiquitin-Conjugating Enzyme E2 N (UEV1A)</td></tr>
<tr><td><strong>Gene</strong></td><td>[UBE2N](/genes/ube2n)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P61079](https://www.uniprot.org/uniprot/P61079)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>1XWH, 2GMI, 3H3Z</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>17 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, Nucleus</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Ubiquitin-conjugating enzyme family</td></tr>
<tr><td><strong>Aliases</strong></td><td>Ubc13, UEV1A, E2-25K</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>
</div>

Overview

UBE2N (Ubiquitin-Conjugating Enzyme E2 N), also known as Ubc13 or UEV1A, is a unique E2 ubiquitin-conjugating enzyme that catalyzes the formation of Lys63-linked polyubiquitin chains[@deng2000]. Unlike classical E2 enzymes that generate Lys48-linked chains for proteasomal degradation, UBE2N produces non-degradative ubiquitin signals that regulate diverse cellular processes including [NF-κB](/entities/nf-kb) signaling, DNA damage repair, and immune responses[@tokunaga2009].

Structure

Domain Architecture

Core UBC Domain: Catalytic core (~150 aa) containing the active site
UEV Domain: N-terminal UEV (Ubiquitin-E2 Variant) domain that lacks catalytic activity
Dimerization Interface: Forms heterodimers with UBE2V1 or UBE2V2

Active Site

Cysteine Residue: Active site cysteine at position 87
Thioester Formation: Forms Ub~UBE2N thioester intermediate
HPCS Motif: Conserved motif in E2 active site

Function

Lys63-Linked Polyubiquitination

UBE2N has distinctive catalytic properties:

Heterodimer Formation: Partners with UBE2V1 (UEV1A) or UBE2V2 (MMS2)

Chain Synthesis: Catalyzes Lys63-linked polyubiquitination

Non-Proteolytic Signaling: Chains serve as signaling platforms rather than degradation signals

Key Pathways

NF-κB Activation: Lys63-Ub chains activate NF-κB transcription factors[@xia2009]
DNA Damage Response: Facilitates recruitment of repair factors to DNA double-strand breaks[@hofmann2009]
Immune Signaling: Regulates T-cell receptor and innate immune signaling
Endosomal Trafficking: Modulates receptor internalization and sorting

Expression

Ubiquitously expressed with high levels in brain and immune tissues
Enriched in postsynaptic densities
Upregulated in response to cellular stress

Role in Neurodegenerative Diseases

Alzheimer's Disease

[Tau](/proteins/tau) Pathology: Alters tau ubiquitination and aggregation dynamics[@tai2012]
Synaptic Dysfunction: Impaired synaptic ubiquitin signaling
Neuroinflammation: NF-κB hyperactivation via UBE2N

Parkinson's Disease

[α-Synuclein](/proteins/alpha-synuclein) Turnover: Regulates [autophagy](/entities/autophagy)-lysosomal degradation
Mitochondrial Quality Control: Involved in mitophagy
Dopaminergic Vulnerability: Altered in PD brain

Amyotrophic Lateral Sclerosis

Protein Aggregation: Dysregulated Ub processing in ALS
RNA Granules: Interaction with ALS-associated RNA-binding proteins
Axonal Transport: Ubiquitin system deficits

Therapeutic Implications

Target Strategy

Inhibitors: Selective UBE2N inhibitors could reduce neuroinflammation

Activators: Enhancing activity may improve protein clearance

Modulation: Fine-tuning NF-κB signaling

Research Status

No UBE2N-targeted drugs in clinical trials
Preclinical studies of NF-κB modulators ongoing
Gene therapy approaches under investigation

Interactions

Protein Partners

UBE2V1: Essential heterodimer partner
TRAF6: NF-κB pathway activator
NEMO: NF-κB essential modifier
RNF8: DNA damage response
OPTN: Autophagy receptor

Background

The study of Ube2N Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

[Deng L, et al, (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/11057907/)

[Tokunaga F, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19136968/)

[Xia ZP, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19675569/)

[Hofmann RM, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19888080/)

[Tai HC, et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22445338/)

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Related Entities

UBE2NPROTEIN

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wiki_page_id	wp-1de46f4be2df
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

11

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

UBE2N Protein

UBE2N Protein — Ubiquitin-Conjugating Enzyme E2 N

Introduction

Overview

UBE2N Protein — Ubiquitin-Conjugating Enzyme E2 N

Introduction

Overview

Structure

Domain Architecture

Active Site

Function

Lys63-Linked Polyubiquitination

Key Pathways

Expression

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Therapeutic Implications

Target Strategy

Research Status

Interactions

Protein Partners

See Also

Background

External Links

References

💬 Discussion