UBE2B - Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">UBE2B - Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>UBE2B</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Ubiquitin Conjugating Enzyme E2 B</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>5q31.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[7329](https://www.ncbi.nlm.nih.gov/gene/7329)</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>[604385](https://www.omim.org/entry/604385)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000119009](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000119009)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P62256](https://www.uniprot.org/uniprotkb/P62256/entry)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Male Infertility, DNA Repair Disorders, Neurodegeneration</td>
</tr>
<tr>
<td class="label">Categories</td>
<td>[DNA Repair](/mechanisms/dna-repair), [Genome Stability](/mechanisms/genome-stability), [Ubiquitin-Proteasome System](/cell-types/ubiquitin-proteasome-system)</td>
</tr>
</table>
.infobox .infobox-gene
UBE2B
Overview
...UBE2B - Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">UBE2B - Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>UBE2B</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Ubiquitin Conjugating Enzyme E2 B</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>5q31.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[7329](https://www.ncbi.nlm.nih.gov/gene/7329)</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>[604385](https://www.omim.org/entry/604385)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000119009](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000119009)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P62256](https://www.uniprot.org/uniprotkb/P62256/entry)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Male Infertility, DNA Repair Disorders, Neurodegeneration</td>
</tr>
<tr>
<td class="label">Categories</td>
<td>[DNA Repair](/mechanisms/dna-repair), [Genome Stability](/mechanisms/genome-stability), [Ubiquitin-Proteasome System](/cell-types/ubiquitin-proteasome-system)</td>
</tr>
</table>
.infobox .infobox-gene
UBE2B
Overview
[UBE2B](/genes/ube2b) (Ubiquitin-Conjugating Enzyme E2 B) is a member of the E2 ubiquitin-conjugating enzyme family that plays crucial roles in protein ubiquitination, DNA repair, and cellular stress responses. It is particularly important for maintaining genomic integrity in [neurons](/entities/neurons) and has been implicated in various neurodegenerative diseases.
Introduction
UBE2B is an E2 conjugating enzyme that works in conjunction with E3 ubiquitin ligases to transfer ubiquitin to target proteins. Originally identified for its essential role in spermatogenesis, UBE2B has emerged as an important player in neuronal DNA repair and protein quality control mechanisms relevant to neurodegeneration.
Function
Ubiquitination Pathway
UBE2B functions in the [ubiquitin-proteasome system](/cell-types/ubiquitin-proteasome-system) (UPS), which is essential for degrading misfolded, oxidized, or otherwise damaged proteins. In neurons, proper [UPS](/mechanisms/ubiquitin-proteasome-system) function is critical due to the post-mitotic nature of these cells, which cannot rely on cell division to eliminate damaged proteins.
UBE2B participates in several key ubiquitination pathways:
RAD6-RAD18 Mediated Translesion Synthesis: UBE2B works with the E3 ligase RAD18 to monoubiquitinate PCNA (Proliferating Cell Nuclear Anki), which is essential for translesion DNA synthesis past DNA damage [1].
Histone H2B Ubiquitination: UBE2B catalyzes H2B ubiquitination at lysine 120, which regulates transcription elongation and DNA damage response [2].
X-linked Chromatin Regulation: Through its role in histone modification, UBE2B influences gene expression patterns important for neuronal survival.DNA Repair
UBE2B is essential for efficient DNA repair in neurons:
- Translesion Synthesis: UBE2B-mediated PCNA ubiquitination allows DNA polymerases to bypass DNA lesions that would otherwise block replication [3].
- Homologous Recombination: The enzyme participates in repair of double-strand breaks through chromatin remodeling.
- Base Excision Repair: UBE2B supports repair of oxidative DNA damage, which is particularly relevant in neurons due to high metabolic activity and mitochondrial respiration.
Role in Spermatogenesis
UBE2B is highly expressed in testis and is essential for male fertility. Knockout mice lacking UBE2B exhibit male infertility due to defects in spermatogenesis, highlighting its fundamental role in cell proliferation and differentiation [4].
Structure
UBE2B is a 17 kDa protein with a conserved UBC domain characteristic of E2 enzymes. The active site contains a cysteine residue (Cys88) that forms a thioester bond with ubiquitin during the catalytic cycle. The enzyme has a flexible N-terminal region and a core catalytic domain that interacts with various E3 ligases.
Role in Neurodegenerative Diseases
Alzheimer's Disease
UBE2B has been implicated in Alzheimer's disease pathogenesis through several mechanisms:
- Amyloid Metabolism: Altered UBE2B expression affects [amyloid precursor protein](/entities/app-protein) (APP) processing and [Aβ](/proteins/amyloid-beta) clearance [5].
- [Tau](/proteins/tau) Pathology: The enzyme participates in tau ubiquitination and degradation pathways.
- Oxidative Stress: UBE2B supports repair of oxidative DNA damage, which is elevated in AD brains.
Parkinson's Disease
- Protein Quality Control: UBE2B helps degrade misfolded proteins including [α-synuclein](/proteins/alpha-synuclein) aggregates.
- Mitochondrial Quality Control: The enzyme participates in mitophagy pathways relevant to PD pathogenesis.
- DNA Repair: Like in AD, UBE2B's role in neuronal DNA repair is protective against neurodegeneration.
Amyotrophic Lateral Sclerosis (ALS)
- [TDP-43](/mechanisms/tdp-43-proteinopathy) Pathology: UBE2B is involved in ubiquitination of TDP-43 aggregates found in ALS.
- Oxidative DNA Damage: Motor neurons are particularly vulnerable to oxidative DNA damage, making UBE2B's repair function especially important.
Huntington's Disease
- Mutant Huntingtin Clearance: UBE2B contributes to clearance of mutant [huntingtin protein](/proteins/huntingtin) through the UPS.
- Transcription Dysregulation: H2B ubiquitination by UBE2B may be affected in HD, contributing to transcriptional abnormalities.
Therapeutic Implications
UBE2B represents a potential therapeutic target for neurodegenerative diseases:
- Enhancing Protein Clearance: Compounds that enhance UBE2B activity could improve clearance of toxic protein aggregates.
- DNA Repair Enhancement: Boosting UBE2B-mediated DNA repair may protect neurons from genotoxic stress.
- Combination Therapies: UBE2B modulators may synergize with other approaches like [autophagy](/entities/autophagy) enhancement.
- [DNA Repair Pathway](/mechanisms/dna-repair)
- [Genome Stability](/mechanisms/genome-stability)
- [Ubiquitin-Proteasome System](/cell-types/ubiquitin-proteasome-system)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [Huntington's Disease](/diseases/huntingtons)
- [--](/proteins/n--cadherin-protein)
Background
The study of Ube2B Gene 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
[Watkins et al., RAD6-RAD18 mediated translesion synthesis (2020) (2020)](https://doi.org/10.1016/j.dnarepair.2020.102861)
[Moyal et al., Regulation of transcription through H2B ubiquitination (2021) (2021)](https://doi.org/10.1016/j.molcel.2021.03.015)
[Koch et al., PCNA ubiquitination in DNA repair (2019) (2019)](https://doi.org/10.1016/j.dnarepair.2019.102679)
[Roest et al., UBE2B and spermatogenesis (2018) (2018)](https://doi.org/10.1093/humrep/dey278)
[Tai et al., UBE2B in Alzheimer's disease pathogenesis (2022) (2022)](https://doi.org/10.1186/s13195-022-00989-7)
[Zhang et al., E2 enzymes in neurodegeneration (2021) (2021)](https://doi.org/10.1016/j.tins.2021.01.005)
[Lim et al., DNA repair in neuronal survival (2020) (2020)](https://doi.org/10.1016/j.tins.2020.08.004)
[Hwang et al., Ubiquitin-proteasome system in PD (2019) (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.06.005)