UBE2B Protein

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UBE2B Protein

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UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">UBE2B Protein</th></tr> [@tiwari2022]
<tr><td><strong>Protein Name</strong></td><td>Ubiquitin-Conjugating Enzyme E2 B</td></tr>
<tr><td><strong>Gene</strong></td><td>[UBE2B](/genes/ube2b)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P49411](https://www.uniprot.org/uniprot/P49411)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>1f45, 2y5w, 3zth</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~17 kDa (152 aa)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Ubc family (E2 conjugating enzymes)</td></tr>
<tr><td><strong>Expression</strong></td><td>Ubiquitous; high in testis, brain</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

...

UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">UBE2B Protein</th></tr> [@tiwari2022]
<tr><td><strong>Protein Name</strong></td><td>Ubiquitin-Conjugating Enzyme E2 B</td></tr>
<tr><td><strong>Gene</strong></td><td>[UBE2B](/genes/ube2b)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P49411](https://www.uniprot.org/uniprot/P49411)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>1f45, 2y5w, 3zth</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~17 kDa (152 aa)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Ubc family (E2 conjugating enzymes)</td></tr>
<tr><td><strong>Expression</strong></td><td>Ubiquitous; high in testis, brain</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

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 surfaces
Active site cysteine: Cys88 forms the thioester bond with ubiquitin
HPPN loop: Contains the active site histidine
Diversified N-terminal region: Confers substrate specificity

The 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/).

Isoforms and Variants

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.

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)

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Related Entities

UBE2BPROTEIN

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slug	proteins-ube2b-protein
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entity_type	protein
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source_table	wiki_pages
wiki_page_id	wp-17635f3be9df
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-ube2b-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 →

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📗 Cite This Artifact

UBE2B Protein

UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B

Overview

UBE2B Protein — Ubiquitin-Conjugating Enzyme E2 B

Overview

Structure

Enzyme Architecture

Isoforms and Variants

Normal Function

Ubiquitination Pathway

Histone Modification

DNA Repair

Spermatogenesis

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Amyotrophic Lateral Sclerosis

Therapeutic Implications

Drug Targets

Biomarker Potential

Genetics

UBE2B Gene

Variants

Research Methods

Detection Techniques

Model Systems

Key Publications

See Also

External Links

References

💬 Discussion