UBE2V2
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">UBE2V2</th>
</tr>
<tr>
<td class="label">Attribute</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>UBE2V2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Ubiquitin-Conjugating Enzyme E2 Variant 2</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>UEV2, MMS2, DDIT1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>8q24.13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7336</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>N/A</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000169139</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P61077</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>147 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~16 kDa</td>
</tr>
<tr>
<td class="label">Ubiquitin Linkage</td>
<td>Function</td>
</tr>
<tr>
<td class="label">K63</td>
<td>Signaling, autophagy, DNA repair</td>
</tr>
<tr>
<td class="label">K48</td>
<td>Proteasomal degradation</td>
</tr>
<tr>
<td class="label">K27</td>
<td>DNA damage response</td>
</tr>
<tr>
<td class="label">Others</td>
<td>Various</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Ube2V2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
UBE2V2 (Ubiquitin-Conjugating Enzyme E2 Variant 2), also known as UEV-2 or MMS2, is a ubiquitin-conjugating enzyme variant that plays a critical role in K63-linked polyubiquitination. Unlike canonical E2 enzymes, UBE2V2 lacks catalytic cysteine residues and functions as a scaffold to facilitate ubiquitin chain assembly. This enzyme is involved in critical cellular processes including DNA damage repair, [NF-κB](/entities/nf-kb) signaling, and stress response—all pathways highly relevant to neurodegenerative diseases. [@klinked2019]
The [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) relies on various E2 enzymes for different types of ubiquitin linkages. K63-linked polyubiquitination, mediated by UBE2V2 in complex with UBE2N, creates non-proteolytic ubiquitin chains that signal for [autophagy](/entities/autophagy), DNA repair, and signal transduction. [@ubenubev2018]
Protein Structure
UBE2V2 belongs to the ubiquitin-conjugating (E2) enzyme family but functions as an E2 variant (UEV) due to the lack of a catalytic cysteine residue.
Key Structural Features
- UEV domain: N-terminal ubiquitin-binding domain that binds ubiquitin
- HPPN loop: Critical for ubiquitin recognition
- UEV2 motif: Mediates interaction with UBE2N
- Phosphorylation sites: Serine/threonine residues regulate function
Molecular Function
K63-Linked Polyubiquitination
UBE2V2 forms a heterodimeric complex with UBE2N (E2 N) to catalyze K63-linked polyubiquitination:
K63-linked ubiquitin chains serve as signaling molecules rather than degradation signals:
Cellular Processes
UBE2V2-mediated ubiquitination regulates:
DNA Damage Response
- Recruitment of repair proteins to damage sites
- Regulation of checkpoint kinases
- Telomere maintenance
NF-κB Signaling
- Activation of IKK complex
- Proinflammatory cytokine production
- Cell survival pathways
Stress Response
- Oxidative stress adaptation
- Proteotoxic stress management
- Autophagy regulation
Immune Function
- T
- Cytokine production-cell activation
- Inflammatory responses
Expression Pattern
Brain Expression
UBE2V2 is expressed throughout the central nervous system:
- [Neurons](/entities/neurons): High expression in cortical and hippocampal neurons
- [Astrocytes](/entities/astrocytes): Moderate expression
- [Microglia](/cell-types/microglia-neuroinflammation): Induced upon neuroinflammation
- Oligodendrocytes: Lower expression
Regulation
UBE2V2 expression is regulated by:
- Transcription factors: p53, NF-κB
- Cellular stress: DNA damage, oxidative stress
- Developmental stage: Higher in developing brain
Role in Neurodegenerative Diseases
Alzheimer's Disease
UBE2V2 is implicated in AD through multiple mechanisms:
- NF-κB activation: Chronic neuroinflammation in AD involves dysregulated NF-κB signaling
- DNA repair deficits: UBE2V2-mediated repair is impaired in AD neurons
- Proteostasis: K63-linked ubiquitination regulates autophagy of [amyloid-beta](/proteins/amyloid-beta) and [tau](/proteins/tau)
Research findings:
- [UBE2V2 expression is altered in AD brain](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)
- K63 ubiquitination is reduced in AD, affecting protein clearance
Parkinson's Disease
UBE2V2 involvement in PD:
- Alpha-synuclein clearance: K63-linked ubiquitination targets [alpha-synuclein](/proteins/alpha-synuclein) for autophagy
- Mitochondrial quality control: UBE2V2 regulates mitophagy
- Neuroinflammation: NF-κB-mediated inflammation contributes to dopaminergic neuron loss
Neuroinflammation
UBE2V2 is a key regulator of inflammatory responses:
- Controls NF-κB activation in microglia
- Regulates cytokine production
- Modulates astrocyte reactivity
Chronic neuroinflammation is a hallmark of:
- Alzheimer's disease
- [Parkinson's disease](/diseases/parkinsons-disease) Amyotrophic lateral sclerosis
- Multiple sclerosis
Therapeutic Implications
Target Potential
UBE2V2 represents a potential therapeutic target for:
Enhancing DNA repair in neurons
Modulating neuroinflammation via NF-κB pathways
Promoting autophagy of toxic protein aggregatesDrug Development
- UBE2V2 activators: Enhance K63-linked ubiquitination
- NF-κB pathway modulators: Indirectly regulate UBE2V2 function
- Autophagy enhancers: Complement UBE2V2's role in protein clearance
Animal Models
- Knockout mice: Viable but show increased sensitivity to DNA damage
- Transgenic models: Overexpression protects against oxidative stress
- Drosophila: Ortholog involved in neurodegeneration models
Cross-Links
- [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)
- [K63-Linked Ubiquitination](/mechanisms/k63-ubiquitination)
- [NF-κB Signaling Pathway](/mechanisms/nf-kb-signaling-neuroinflammation)mechanisms/nf-kb-signaling-neuroinflammation)
- [DNA Damage Response in Neurodegeneration](/mechanisms/dna-damage-response)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
See Also
- [Ubiquitin-Conjugating Enzyme](/proteins/ube2-enzyme) - Family of E2 enzymes
- [UBE2N](/genes/ube2n) - Partner E2 enzyme
- [UBE2V1](/genes/ube2v1) - Paralog E2 enzyme
- [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system) - Protein degradation pathway
- [NF-kB Signaling](/mechanisms/nf-kb-signaling-neuroinflammation)) - Inflammatory pathway
External Links
- [NCBI Gene: UBE2V2](https://www.ncbi.nlm.nih.gov/gene/7336)
- [UniProt: Q15819](https://www.uniprot.org/uniprotkb/Q15819)
- [Ensembl: ENSG00000107281](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107281)
- [GeneCards: UBE2V2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=UBE2V2)
Background
The study of Ube2V2 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.
References
[Unknown, UBE2V2 in Alzheimer's disease brain (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)
[Unknown, K63-linked ubiquitination in neurodegeneration (2019)](https://doi.org/10.1016/j.tcb.2019.08.005)
[Unknown, UBE2N-UBE2V2 complex in DNA damage response (2018)](https://doi.org/10.1016/j.dnarep.2018.12.003)
[Unknown, NF-κB in neurodegenerative diseases (2019)](https://doi.org/10.1038/s41582-019-0172-6)
[Unknown, Ubiquitin variants in Parkinson's disease (2019)](https://doi.org/10.1093/brain/awz132)
[Unknown, K63 ubiquitination and autophagy in AD (2020)](https://doi.org/10.1111/jnc.14854)
[Unknown, Microglial NF-κB activation in neurodegeneration (2020)](https://doi.org/10.1016/j.tins.2020.03.008)
[Unknown, Therapeutic targeting of ubiquitin pathways (2019)](https://doi.org/10.1038/s41573-019-0036-1)