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.
The Allen Brain Atlas 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
[^2]
[^3]
Gene: [UBE2C](/genes/ube2c)
[^4]
UniProt ID: [O00712](https://www.uniprot.org/uniprot/O00712)
[^5]
PDB ID: [1FZV](https://www.rcsb.org/structure/1FZV)
Molecular Weight: ~19.6 kDa (179 amino acids)
Subcellular Localization: Cytoplasm, nucleus
Protein Family: UBC family, E2 C subfamily
Associated Diseases: [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Cancer
UBE2C is a member of the E2 ubiquitin-conjugating enzyme family that functions in the ubiquitin-proteasome system. 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.
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
- α/β fold with active site cysteine
- Conserved HPPN motif
- Dimerization capability
- Multiple conformations for substrate binding
| Residue |
Function |
| Cys91 |
Catalytic cysteine |
| Asp125 |
Catalytic aspartate |
| His127 |
Catalytic histidine |
UBE2C functions in ubiquitin transfer:
- Priming substrates for ubiquitination [^7]
- K48-linked and K11-linked chain formation
- Cell cycle regulation through protein degradation
- APC/C substrate ubiquitination
| Target |
Function |
Degradation Pathway |
| Cyclin B |
Cell cycle |
APC/C-Cdh1 |
| Securin |
Metaphase-anaphase |
APC/C-Cdc20 |
| Aurora B |
Mitosis |
APC/C |
- Expressed in neural progenitor cells
- Role in neurogenesis
- Cell cycle control in neurons
- DNA damage response
- Altered UBE2C levels in AD brain [^8]
- Role in tau ubiquitination
- Cell cycle re-entry in neurons
- Implicated in amyloid-β metabolism
- Dysregulated in PD models [^9]
- Role in α-synuclein degradation
- PINK1/Parkin pathway connections
- Mitochondrial protein quality control
- Altered ubiquitination in ALS [^10]
- Role in TDP-43 turnover
- Aggregate clearance pathways
- RNA processing protein degradation
- E2 enzyme inhibitors
- APC/C modulators
- Ubiquitin system enhancers
- Combination therapies
- Ubiquitination assays
- E2 enzyme activity kits
- Structural studies of E2-substrate complexes