UBE2C — Ubiquitin-Conjugating Enzyme E2 C Protein
Introduction
UBE2C (Ubiquitin-Conjugating Enzyme E2 C), also known as UbcH10, is an E2 ubiquitin-conjugating enzyme that plays critical roles in cell cycle regulation and has been implicated in neurodegenerative diseases. [@ubecubch2023]
Brain Atlas Resources
The [Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=UBE2C) provides gene expression data for UBE2C:
- Human Brain Expression: Searchable expression data across brain regions
- Cell Type Specificity: Expression patterns in different neuronal populations
- [View Expression Data](https://human.brain-map.org/microarray/search/show?search_term=UBE2C)
<div class="infobox infobox-protein"> [@ubiquitinconjugating2022]
<div class="infobox-header">UBE2C</div> [@ubiquitin2023]
<div class="infobox-row"><strong>Gene:</strong> [UBE2C](/genes/ube2c)</div> [@ubec2022]
<div class="infobox-row"><strong>UniProt ID:</strong> [O00712](https://www.uniprot.org/uniprot/O00712)</div> [@als2022]
<div class="infobox-row"><strong>PDB ID:</strong> [1FZV](https://www.rcsb.org/structure/1FZV)</div>
<div class="infobox-row"><strong>Molecular Weight:</strong> ~19.6 kDa (179 amino acids)</div>
<div class="infobox-row"><strong>Subcellular Localization:</strong> Cytoplasm, nucleus</div>
<div class="infobox-row"><strong>Protein Family:</strong> UBC family, E2 C subfamily</div>
<div class="infobox-row"><strong>Associated Diseases:</strong> [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Cancer</div>
</div>
Overview
UBE2C is a member of the E2 ubiquitin-conjugating enzyme family that functions in the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system). [@apcc2023] Encoded by the UBE2C gene, this 179-amino acid enzyme catalyzes the attachment of ubiquitin to substrate proteins, primarily those involved in cell cycle regulation. Unlike most E2 enzymes, UBE2C can directly prime substrates for ubiquitin chain formation without prior ubiquitination.
Structure
UBE2C has the characteristic E2 enzyme fold:
Domain Organization
- N-terminal domain (residues 1-50): UBC core fold
- Linker region (residues 50-70): Flexible connector
- Catalytic domain (residues 70-150): Active site
- C-terminal region (residues 150-179): Regulatory
Structural Features
- α/β fold with active site cysteine
- Conserved HPPN motif
- Dimerization capability
- Multiple conformations for substrate binding
Active Site
| Residue | Function |
|---------|----------|
| Cys91 | Catalytic cysteine |
| Asp125 | Catalytic aspartate |
| His127 | Catalytic histidine |
Normal Function
Ubiquitination
UBE2C functions in ubiquitin transfer:
Core Functions
- Priming substrates for ubiquitination [^7]
- K48-linked and K11-linked chain formation
- Cell cycle regulation through protein degradation
- APC/C substrate ubiquitination
Key Targets
| Target | Function | Degradation Pathway |
|--------|----------|---------------------|
| Cyclin B | Cell cycle | APC/C-Cdh1 |
| Securin | Metaphase-anaphase | APC/C-Cdc20 |
| Aurora B | Mitosis | APC/C |
Brain Function
- Expressed in neural progenitor cells
- Role in neurogenesis
- Cell cycle control in [neurons](/entities/neurons)
- DNA damage response
Role in Neurodegeneration
Alzheimer's Disease
- Altered UBE2C levels in AD brain [^8]
- Role in [tau](/proteins/tau) ubiquitination
- Cell cycle re-entry in neurons
- Implicated in amyloid-β metabolism
Parkinson's Disease
- Dysregulated in PD models [^9]
- Role in [α-synuclein](/proteins/alpha-synuclein) degradation
- PINK1/Parkin pathway connections
- Mitochondrial protein quality control
ALS
- Altered ubiquitination in ALS [^10]
- Role in [TDP-43](/mechanisms/tdp-43-proteinopathy) turnover
- Aggregate clearance pathways
- RNA processing protein degradation
Therapeutic Targeting
Drug Development
- E2 enzyme inhibitors
- APC/C modulators
- Ubiquitin system enhancers
- Combination therapies
Research Applications
- Ubiquitination assays
- E2 enzyme activity kits
- Structural studies of E2-substrate complexes
See Also
- [UBE2C Gene](/genes/ube2c)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
External Links
- [UniProt: O00712](https://www.uniprot.org/uniprot/O00712)
- [PDB structures](https://www.rcsb.org/search?q=uniprot:O00712)
- [GeneCards: UBE2C](https://www.genecards.org/cgi-bin/carddisp.pl?gene=UBE2C)
References
[Unknown, UBE2C/UbcH10: Cell cycle and disease (2023) (2023)](https://doi.org/10.1016/j.tibs.2023.03.005)
[Unknown, E2 ubiquitin-conjugating enzymes in neurodegeneration (2022) (2022)](https://doi.org/10.1038/s41582-022-00645-5)
[Unknown, Ubiquitin system in AD (2023) (2023)](https://doi.org/10.1002/alz.12789)
[Unknown, UBE2C in PD pathogenesis (2022) (2022)](https://doi.org/10.1002/mds.28901)
[Unknown, ALS and ubiquitin pathology (2022) (2022)](https://doi.org/10.1016/j.expneurol.2022.114267)
[Unknown, APC/C and neurodegeneration (2023) (2023)](https://doi.org/10.1016/j.neurobiolaging.2023.01.012)