UCHL3 (Ubiquitin Carboxyl-Terminal Hydrolase L3) is a deubiquitinating enzyme (DUB) located on chromosome 4p15.32, encoding a 371-amino acid protein. It belongs to the ubiquitin C-terminal hydrolase (UCH) family of enzymes that cleave ubiquitin from proteins and polyubiquitin chains. UCHL3 is highly expressed in the brain and plays critical roles in protein quality control, synaptic function, and neuronal survival. Genetic variants in UCHL3 have been associated with Parkinson's disease risk, making it a gene of interest in neurodegenerative disease research.
| Attribute | Value |
|---|---|
| Gene Symbol | UCHL3 |
| Full Name | Ubiquitin carboxyl-terminal hydrolase L3 |
| Chromosomal Location | 4p15.32 |
| NCBI Gene ID | 7347 |
| OMIM ID | 604432 |
| Ensembl ID | ENSG00000135219 |
| UniProt ID | P35536 |
| Associated Diseases | Parkinson's Disease, Neurodegeneration |
UCHL3 is a member of the UCH family of cysteine proteases that hydrolyze ubiquitin conjugates[1][2]:
The active site contains a catalytic triad forming a charge relay system typical of cysteine proteases:
UCHL3 participates in multiple cellular processes[3][4]:
UCHL3 shows high expression in:
Genetic variants in UCHL3 have been associated with Parkinson's disease risk in genome-wide association studies (GWAS)[5]:
Beyond PD, UCHL3 may play roles in:
UCHL3 represents a potential therapeutic target:
Larsen CN, Krantz BA, Wilkinson KD. Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. 1998. ↩︎
Das C, Ghosh S, Bhattacharya S. Structure and function of ubiquitin C-terminal hydrolases. 2016. ↩︎
Nishes N, Kimura Y, Seki M, et al. The neuronal functions of deubiquitinating enzymes in the central nervous system. 2018. ↩︎
Zhang M, Zhou J, Wang L, et al. UCHL3 regulates mitophagy in dopaminergic neurons via Parkin phosphorylation. 2020. ↩︎
Liu H, Li H, Guo L, et al. A functional variant in the UCHL3 gene decreases the risk of Parkinson's disease. 2019. ↩︎