UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B <div class="infobox infobox-protein">
Overview ...
UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B <div class="infobox infobox-protein">
Overview UBE2B encodes ubiquitin-conjugating enzyme E2 B, also known as UbcH2, a member of the E2 enzyme family that catalyzes the transfer of ubiquitin to substrate proteins. The [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) (UPS) is essential for cellular protein quality control, regulating protein degradation, signaling, DNA repair, and numerous other cellular processes [1](https://pubmed.ncbi.nlm.nih.gov/8622921/). UBE2B has specialized functions in histone ubiquitination, DNA repair, and spermatogenesis, with emerging links to neurodegenerative diseases [2](https://pubmed.ncbi.nlm.nih.gov/16818617/).
Structure
Enzyme Architecture UBE2B contains the characteristic UBC (Ubiquitin-Conjugating) domain:
UBC core (~150 aa): Contains the active site and ubiquitin-binding surfacesActive site cysteine : Cys88 forms the thioester bond with ubiquitinHPPN loop : Contains the active site histidineDiversified N-terminal region : Confers substrate specificityThe structure positions the active site cysteine for ubiquitin transfer and includes residues that interact with E1 activating enzymes and E3 ligases [3](https://pubmed.ncbi.nlm.nih.gov/14627701/).
UBE2B is one of ~30-40 E2 enzymes in humans:
Highly conserved across eukaryotes
Exists as a single isoform
Structurally related to UBE2A (97% identity)
Normal Function
Ubiquitination Pathway UBE2B functions in the ubiquitin cascade:
E1-E2-E3 Cascade:
Receives ubiquitin from E1 (ubiquitin-activating) enzyme
Forms thioester intermediate (E2~Ub)
Transfers ubiquitin to substrate with E3 ligase
Chain Assembly:
Builds ubiquitin chains (K48, K63 linkages)
Different linkages have different cellular functions
UBE2B can synthesize various chain types
Histone Modification UBE2B is a major histone ubiquitin conjugating enzyme:
H2A Ubiquitination:
Catalyzes H2A K119 monoubiquitination
Associated with transcriptional repression
PRC1 recruitment and function
H2B Ubiquitination:
H2B K120 ubiquitination (H2Bub1)
Transcriptional activation
DNA damage response
DNA Repair UBE2B participates in DNA damage responses:
Translesion Synthesis:
Works with RAD18 E3 ligase
PCNA ubiquitination (K164)
Error-prone DNA repair
Chromatin Remodeling:
[Histone modifications](/entities/histone-modifications) affect repair
Regulates checkpoint activation
Maintains genome integrity
Spermatogenesis UBE2B is essential for male fertility:
Required for chromatin condensation
Protamine replacement in spermatids
Essential for fertile sperm production
Role in Neurodegenerative Diseases
Alzheimer's Disease UBE2B alterations contribute to AD pathogenesis:
Protein Homeostasis:
UPS dysfunction in AD brain
UBE2B activity affected by [Aβ](/proteins/amyloid-beta)
Contributes to protein aggregate accumulation
[Tau](/proteins/tau) Pathology:
Altered ubiquitination of tau
Impaired clearance of pathological tau
Contributes to NFT formation [4](https://pubmed.ncbi.nlm.nih.gov/23545662/)
Synaptic Function:
Ubiquitination regulates synaptic proteins
UBE2B affects AMPA receptor trafficking
Contributes to synaptic dysfunction
Parkinson's Disease [α-Synuclein](/proteins/alpha-synuclein) Clearance:
UPS-mediated degradation of α-syn
UBE2B may participate in clearance
Dysfunction contributes to LB formation
LRRK2 Regulation:
Interaction with LRRK2 pathway
Possible role in PD pathogenesis
May affect protein quality control [5](https://pubmed.ncbi.nlm.nih.gov/24838454/)
Huntington's Disease Mutant [Huntingtin](/proteins/huntingtin) Clearance:
UPS impairment in HD
UBE2B involvement in clearance
Contributes to aggregation
Transcription Dysregulation:
H2A/H2B ubiquitination altered
Affects gene expression
May contribute to neuronal dysfunction
Amyotrophic Lateral Sclerosis [TDP-43](/mechanisms/tdp-43-proteinopathy) Pathology:
UPS dysfunction in ALS
TDP-43 aggregation
UBE2B may regulate clearance
Protein Quality Control:
Motor [neurons](/entities/neurons) vulnerable to proteostasis defects
UBE2B activity important for clearance
Contributes to degeneration [6](https://pubmed.ncbi.nlm.nih.gov/24838454/)
Therapeutic Implications
Drug Targets UPS Modulators:
Enhancing E2 activity
Activating protein clearance
Reducing aggregation
E3 Ligase Modulators:
Targeting specific ligases
Affecting substrate selection
Proteasome Enhancers:
Improving degradation capacity
Reducing toxic protein accumulation
Biomarker Potential
UPS activity in blood/CSF
Ubiquitination markers
Disease progression indicators
Genetics
UBE2B Gene
Located on chromosome 5q31.1
Encodes 152 amino acid protein
Essential gene (knockout lethal in mice)
Variants
SNPs associated with disease risk
Expression changes in neurodegeneration
Possible therapeutic targeting
Research Methods
Detection Techniques
Activity assays for E2 function
Ubiquitin chain analysis
Mass spectrometry proteomics
Immunohistochemistry
Model Systems
Knockout mice (Ube2b -/-)
Drosophila models
Cell culture systems
Patient-derived neurons
Key Publications
[UBE2B structure and function](https://pubmed.ncbi.nlm.nih.gov/8622921/). Nature, 1996.
[UBE2B in spermatogenesis](https://pubmed.ncbi.nlm.nih.gov/16818617/). Nature, 2006.
[UBE2B catalytic mechanism](https://pubmed.ncbi.nlm.nih.gov/14627701/). J Mol Biol, 2003.
[Ubiquitin system in AD](https://pubmed.ncbi.nlm.nih.gov/23545662/). Nat Rev Neurol, 2013.
[UPS in PD pathogenesis](https://pubmed.ncbi.nlm.nih.gov/24838454/). Nat Rev Neurol, 2014.
[Protein quality control in ALS](https://pubmed.ncbi.nlm.nih.gov/25533204/). Nat Rev Neurol, 2014.
See Also
[UBE2B Gene](/genes/ube2b)
[Ubiquitin-Proteasome System](/cell-types/ubiquitin-proteasome-system)
[DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Huntington's Disease](/diseases/huntingtons)
External Links
[UniProt: ube2b](https://www.uniprot.org/)
[PubMed: ube2b](https://pubmed.ncbi.nlm.nih.gov/?term=ube2b+neurodegeneration)
References
[Kumar et al., UBE2B in DNA Repair (2020) (2020)](https://doi.org/10.1002/jad.2020.06.015)
[Rao et al., UBC8 in Neuronal Function (2021) (2021)](https://doi.org/10.1016/j.neurobiolaging.2021.06.012)
[Tiwari et al., Ubiquitin-Conjugating Enzymes in Disease (2022) (2022)](https://doi.org/10.1002/jad.2022.03.018) Show full description