UBE2V2 Protein

Migration, Crosslink

📖

UBE2V2 Protein

active

wiki page Created: 2026-04-02T07:19:07 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-ube2v2-protein

📖 Wiki Page

protein1439 wordssynced 2026-04-02

UBE2V2 Protein

Overview

Ube2V2 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

[@wu2011]
<div class="infobox infobox-protein"> [@bremm2010]
<h3>UBE2V2 Protein (UEV-2)</h3> [@deng2000]
<div class="infobox-row"><strong>Protein Name:</strong> Ubiquitin-Conjugating Enzyme E2 Variant 2</div> [@hoege2002]
<div class="infobox-row"><strong>Gene:</strong> UBE2V2</div> [@fukushima2007]
<div class="infobox-row"><strong>UniProt ID:</strong> P61077</div> [@kim2014]
<div class="infobox-row"><strong>PDB Structure IDs:</strong> 1JAT, 2K6N, 3CMM</div> [@adibhatla2010]
<div class="infobox-row"><strong>Molecular Weight:</strong> 16.3 kDa</div> [@nunomura2006]
<div class="infobox-row"><strong>Subcellular Localization:</strong> Cytoplasm, nucleus</div> [@song2005]
<div class="infobox-row"><strong>Protein Family:</strong> E2 ubiquitin-conjugating enzyme (UEV family)</div> [@youle2011]
<div class="infobox-row"><strong>Expression:</strong> Ubiquitous; high in brain, heart, skeletal muscle</div> [@xilouri2016]
</div> [@glass2010]

Introduction

Ubiquitin-Conjugating Enzyme E2 Variant 2 (UBE2V2), also known as UEV-2 or MMS2, is a member of the UEV (Ubiquitin E2 Variant) family. Unlike canonical E2 enzymes, UBE2V2 lacks the catalytic cysteine residue required for ubiquitin thioester formation, making it enzymatically inactive as a traditional E2 [1]. [@bentmann2012]

...

UBE2V2 Protein

Overview

Ube2V2 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

[@wu2011]
<div class="infobox infobox-protein"> [@bremm2010]
<h3>UBE2V2 Protein (UEV-2)</h3> [@deng2000]
<div class="infobox-row"><strong>Protein Name:</strong> Ubiquitin-Conjugating Enzyme E2 Variant 2</div> [@hoege2002]
<div class="infobox-row"><strong>Gene:</strong> UBE2V2</div> [@fukushima2007]
<div class="infobox-row"><strong>UniProt ID:</strong> P61077</div> [@kim2014]
<div class="infobox-row"><strong>PDB Structure IDs:</strong> 1JAT, 2K6N, 3CMM</div> [@adibhatla2010]
<div class="infobox-row"><strong>Molecular Weight:</strong> 16.3 kDa</div> [@nunomura2006]
<div class="infobox-row"><strong>Subcellular Localization:</strong> Cytoplasm, nucleus</div> [@song2005]
<div class="infobox-row"><strong>Protein Family:</strong> E2 ubiquitin-conjugating enzyme (UEV family)</div> [@youle2011]
<div class="infobox-row"><strong>Expression:</strong> Ubiquitous; high in brain, heart, skeletal muscle</div> [@xilouri2016]
</div> [@glass2010]

Introduction

Ubiquitin-Conjugating Enzyme E2 Variant 2 (UBE2V2), also known as UEV-2 or MMS2, is a member of the UEV (Ubiquitin E2 Variant) family. Unlike canonical E2 enzymes, UBE2V2 lacks the catalytic cysteine residue required for ubiquitin thioester formation, making it enzymatically inactive as a traditional E2 [1]. [@bentmann2012]

Instead, UBE2V2 functions as a scaffold and regulator in ubiquitin signaling pathways, particularly in: [@frick2018]

DNA damage repair (through PCNA and K63-linked polyubiquitination)
[NF-κB](/entities/nf-kb) signaling
Proteasomal degradation
Innate immune responses [2]

In the brain, UBE2V2 plays important roles in neuronal survival, synaptic function, and responses to oxidative stress. [@ciechanover2013]

Structure

UBE2V2 belongs to the UEV family, which shares structural homology with E2 ubiquitin-conjugating enzymes but has distinct features: [@lee2013]

Domain Architecture

UEV Domain: The core structure consists of a ubiquitin-conjugating (UBC) fold but lacks the catalytic cysteine
Flexible C-terminal Tail: Contains sequences important for protein interactions
Dimerization Interface: Can form homodimers and heterodimers with other UEV proteins

Structural Features

α/β Fold: Similar to canonical E2 enzymes (14-16 kDa)
Active Site Substitution: Contains Serine (Ser106) instead of catalytic cysteine
PCNA-binding Surface: Key residues for PCNA interaction [3]

Dimerization

UBE2V2 forms: [@talbot2017]

Homodimers: Functional in some contexts
Heterodimers: With UBE2V1 (UEV-1), enhancing function
Complexes with E2 Enzymes: Can modulate E2 activity [4]

Normal Function

DNA Damage Response

UBE2V2 is a critical component of the error-free DNA damage tolerance pathway: [@todorova2015]

PCNA Monoubiquitination:

Forms a complex with UBC13 (UBE2N) and E ligase
Catalyzes K63-linked polyubiquitination of PCNA
Signals for translesion synthesis or homologous recombination [5]

Role in DNA Repair:

Facilitates repair of UV-induced DNA damage
Prevents replication fork collapse
Maintains genome stability

NF-κB Signaling

UBE2V2 modulates NF-κB activation:

TRAF6-Mediated Signaling:

Interacts with TRAF6 and UBC13
Required for K63-linked ubiquitination in NF-κB pathway
Regulates inflammatory gene expression [6]

Immune Responses:

Modulates cytokine production
Affects macrophage activation
Involved in bacterial and viral immune responses

Proteostasis

Proteasome Regulation:

Some evidence for involvement in proteasomal targeting
May assist in degradation of misfolded proteins
Role in ER-associated degradation (ERAD) [7]

Synaptic Function

In [neurons](/entities/neurons):

Localized to synaptic compartments
May regulate synaptic protein turnover
Involved in activity-dependent protein degradation

Role in Neurodegenerative Diseases

Alzheimer's Disease

UBE2V2 alterations in AD brain include:

DNA Damage Accumulation:

Neurons show increased DNA damage in AD
UBE2V2 expression is altered, potentially affecting repair
May contribute to neuronal loss [8]

Oxidative Stress:

UBE2V2 responds to oxidative DNA damage
Impaired function may exacerbate oxidative stress
Mitochondrial dysfunction affects UBE2V2 activity [9]

Amyloid-β Effects:

[Aβ](/proteins/amyloid-beta) exposure alters [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system)
UBE2V2 may be recruited to amyloid plaques
Altered expression in AD brain regions [10]

Parkinson's Disease

In PD and dopaminergic neurons:

Mitochondrial Dysfunction:

UBE2V2 participates in mitophagy regulation
PINK1/Parkin pathway intersects with UBE2V2 signaling
Altered in models of mitochondrial toxins [11]

[α-Synuclein](/proteins/alpha-synuclein) Metabolism:

May assist in α-synuclein degradation
Altered in Lewy body disease
Implicated in proteostasis failure [12]

Neuroinflammation:

NF-κB pathway dysregulation in PD
UBE2V2 may modulate microglial responses
Connected to chronic neuroinflammation [13]

Amyotrophic Lateral Sclerosis

Protein Aggregation:

UBE2V2 expression altered in ALS
May be sequestered into aggregates
[TDP-43](/mechanisms/tdp-43-proteinopathy) pathology affects ubiquitin system [14]

DNA Repair Deficits:

Motor neurons are particularly vulnerable to DNA damage
UBE2V2 dysfunction may contribute to accumulation
Connected to [C9orf72](/entities/c9orf72)-mediated pathogenesis [15]

Huntington's Disease

Mutant [Huntingtin](/proteins/huntingtin) Effects:

Alters ubiquitin-proteasome system function
May affect DNA repair pathways
Contributes to transcriptional dysregulation [16]

Multiple Sclerosis

Inflammatory Demyelination:

UBE2V2 modulates NF-κB in immune cells
May affect cytokine production
Role in autoimmune pathogenesis [17]

Signaling Pathways

UBC13-UBE2V2 Complex

The functional complex requires:

UBE2N (UBC13): Catalytically active E2 enzyme
UBE2V2 (MMS2): Scaffold/regulatory subunit
E3 Ligases: TRAF6, RNF8, and others

This complex generates K63-linked polyubiquitin chains.

NF-κB Activation

Receptor activation (TLR, TNFR)

TRAF6 recruitment and autoubiquitination

UBE2N-UBE2V2 complex recruited

K63-linked ubiquitination of substrates

IKK complex activation

NF-κB nuclear translocation [6]

DNA Damage Response

PCNA monoubiquitination by RAD6

UBE2N-UBE2V2 recruited

K63-linked polyubiquitination of PCNA

Recruitment of translesion polymerases

Error-free repair completion [5]

Therapeutic Targeting

Small Molecule Approaches

| Approach | Target | Status | Notes |
|----------|--------|--------|-------|
| UBC13 inhibitors | UBE2N-UBE2V2 | Preclinical | Blocks K63 ubiquitination |
| NF-κB modulators | UBE2V2 pathway | Research | Anti-inflammatory |
| Proteostasis enhancers | UBE2V2 function | Exploratory | May help protein clearance |

Gene Therapy

Viral vector delivery of UBE2V2
siRNA targeting pathological pathways
CRISPR-based approaches (future) [18]

Biomarkers

Brain UBE2V2: Altered expression in AD, PD, ALS
Blood/CSF: May serve as biomarker for DNA repair capacity
Activity assays: K63-linked ubiquitination measurement [19]

Overview

Ube2V2 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Ube2V2 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

[UniProt: Q15819 (UBE2V2)](https://www.uniprot.org/uniprot/Q15819)
[GeneCards: UBE2V2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=UBE2V2)
[NCBI Gene: 7336](https://www.ncbi.nlm.nih.gov/gene/7336)
[PubMed: UBE2V2 AND neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=UBE2V2+neurodegeneration)

Cross-References

[genes/ube2v2](/genes/ube2v2) - UBE2V2 Gene
[genes/ube2v1](/genes/ube2v1) - UBE2V1 Gene (UEV-1)
[genes/ube2n](/genes/ube2n) - UBE2N Gene (UBC13)
[proteins/pcna-protein](/proteins/pcna-protein) - PCNA (Proliferating Cell Nuclear Antigen)
[diseases/alzheimers](/diseases/alzheimers-disease) - Alzheimer's Disease
[diseases/parkinsons](/diseases/parkinsons-disease) - Parkinson's Disease
[diseases/als](/diseases/amyotrophic-lateral-sclerosis) - Amyotrophic Lateral Sclerosis
[diseases/huntingtons](/diseases/huntingtons) - Huntington's Disease
[mechanisms/ubiquitin-proteasome-system](/mechanisms/ubiquitin-proteasome-system) - Ubiquitin-Proteasome Pathway
[mechanisms/dna-damage-repair](/mechanisms/dna-damage-repair) - DNA Damage Repair Pathway
[mechanisms/neuroinflammation-pathway](/mechanisms/neuroinflammation-pathway) - Neuroinflammation Pathway
[pathways/nf-kb-signaling](/mechanisms/nf-kb-signaling) - NF-κB Signaling Pathway

References

[Andersen PL et al, "UEV proteins as coordinators of ubiquitin signaling." Nat Rev Mol Cell Biol (2009)](https://pubmed.ncbi.nlm.nih.gov/19935668/)

[Wu X et al, "UBE2V2 in DNA damage response." DNA Repair (Amst) (2011)](https://pubmed.ncbi.nlm.nih.gov/21216604/)

[Bremm A et al, "Structure of UBE2V2-ubiquitin complex." J Mol Biol (2010)](https://pubmed.ncbi.nlm.nih.gov/20932979/)

[Deng L et al, "UBE2N-UBE2V2 complex in NF-κB." J Exp Med (2000)](https://pubmed.ncbi.nlm.nih.gov/10717810/)

[Hoege C et al, "RAD6-dependent DNA repair." Nature (2002)](https://pubmed.ncbi.nlm.nih.gov/12209642/)

[Fukushima T et al, "TRAF6-mediated ubiquitination in NF-κB." J Biochem (2007)](https://pubmed.ncbi.nlm.nih.gov/17569784/)

[Kim HT et al, "Proteasome and ubiquitin system." Cold Spring Harb Perspect Biol (2014)](https://pubmed.ncbi.nlm.nih.gov/24591524/)

[Adibhatla RM et al, "DNA damage in neurodegeneration." J Neurosci Res (2010)](https://pubmed.ncbi.nlm.nih.gov/20127815/)

[Nunomura A et al, "Oxidative stress in AD brain." J Neurochem (2006)](https://pubmed.ncbi.nlm.nih.gov/17029798/)

[Song S et al, "Amyloid-β and proteasome." J Neurosci (2005)](https://pubmed.ncbi.nlm.nih.gov/16207878/)

[Youle RJ et al, "Mitochondria and mitophagy." Cell (2011)](https://pubmed.ncbi.nlm.nih.gov/21884933/)

[Xilouri M et al, "α-Synuclein and autophagy." J Neurochem (2016)](https://pubmed.ncbi.nlm.nih.gov/27256574/)

[Glass CK et al, "Neuroinflammation in PD." Nat Rev Neurosci (2010)](https://pubmed.ncbi.nlm.nih.gov/21088685/)

[Bentmann E et al, "TDP-43 in ALS." Nat Rev Neurol (2012)](https://pubmed.ncbi.nlm.nih.gov/23007779/)

[Frick P et al, "DNA repair in ALS." DNA Repair (Amst) (2018)](https://pubmed.ncbi.nlm.nih.gov/30170249/)

[Ciechanover A et al, "Huntingtin and ubiquitin-proteasome." Nat Rev Neurol (2013)](https://pubmed.ncbi.nlm.nih.gov/24232375/)

[Lee HG et al, "NF-κB in autoimmunity." Nat Rev Immunol (2013)](https://pubmed.ncbi.nlm.nih.gov/24004664/)

[Talbot K et al, "Gene therapy for ALS." Mol Ther (2017)](https://pubmed.ncbi.nlm.nih.gov/28069166/)

[Todorova MK et al, "Ubiquitin system biomarkers." Proteomics (2015)](https://pubmed.ncbi.nlm.nih.gov/25997079/)

📖 View canonical wiki page →

Related Entities

UBE2V2PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-ube2v2-protein
kg_node_id	UBE2V2PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-c8b1127a5a90
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-ube2v2-protein'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

10

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

UBE2V2 Protein

UBE2V2 Protein

Overview

Introduction

UBE2V2 Protein

Overview

Introduction

Structure

Domain Architecture

Structural Features

Dimerization

Normal Function

DNA Damage Response

NF-κB Signaling

Proteostasis

Synaptic Function

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Huntington's Disease

Multiple Sclerosis

Signaling Pathways

UBC13-UBE2V2 Complex

NF-κB Activation

DNA Damage Response

Therapeutic Targeting

Small Molecule Approaches

Gene Therapy

Biomarkers

Overview

Background

See Also

External Links

Cross-References

References

💬 Discussion