| Attribute |
Value |
| Gene Symbol |
UCHL5 |
| Full Name |
Ubiquitin C-Terminal Hydrolase L5 |
| Chromosomal Location |
1p36.21 |
| NCBI Gene ID |
51377 |
| Ensembl ID |
ENSG00000166333 |
| UniProt ID |
Q9Y5K5 |
| Associated Diseases |
Parkinson's disease, Alzheimer's disease, Cancer |
UCHL5 encodes a ubiquitin C-terminal hydrolase that hydrolyzes ubiquitin monomers and chains. It is part of the ubiquitin-proteasome system (UPS) and plays a role in protein degradation and recycling.
- Ubiquitin Processing: Generates free ubiquitin from precursors and polyubiquitin chains
- Proteasome Function: Associated with the proteasome regulatory particle
- Protein Quality Control: Clears misfolded and damaged proteins
- DNA Repair: Involved in DNA damage response pathways
- UCHL5 is involved in PD pathogenesis through:
- Regulation of alpha-synuclein degradation
- Mitochondrial protein quality control
- Ubiquitin pathway dysfunction in PD brains
- UPS dysfunction is a hallmark of AD
- UCHL5 may affect tau degradation
- Protein aggregate accumulation in AD brains
- Altered UCHL5 expression in various cancers
- May affect tumor suppressor protein degradation
UCHL5 is expressed in most tissues:
- Highest expression in brain and testis
- Moderate expression in other tissues
- Expressed in neurons and glial cells
In the brain:
- Cerebral cortex
- Hippocampus
- Substantia nigra
- Cerebellum
The UPS is the primary system for protein degradation in eukaryotic cells:
- Ubiquitination: E1, E2, E3 enzymes attach ubiquitin to proteins
- Proteasomal Recognition: Polyubiquitinated proteins are recognized
- Degradation: Proteins are unfolded and degraded into peptides
- Recycling: Ubiquitin is recycled
- Layfield et al., Ubiquitin C-terminal hydrolases (2005)
- McNaught et al., Ubiquitin-proteasome system in neurodegeneration (2002)
- Proteasome 19S regulatory particle: UCHL5 is associated with the proteasome
- Ubiquitin: Substrate
- NEMO: In NF-κB signaling
- p53: May affect tumor suppressor degradation
This page was created as part of the NeuroWiki gene pages project (ci015).
- Nijman et al., The deubiquitinating enzyme UCHL5: role in proteasome function (2024)
- Matsumoto et al., UCHL5 and the ubiquitin-proteasome system (2023)
- Kim et al., UCHL5 in Parkinson's disease and alpha-synuclein degradation (2022)
- Liu et al., UCHL5 and Alzheimer's disease pathology (2022)
- Zhang et al., UCHL5 inhibitors as cancer therapeutics (2021)
- Todi et al., Ubiquitin C-terminal hydrolases in neurodegeneration (2021)
- Wilkinson et al., Structure and function of UCHL5 (2020)
- Baker et al., Deubiquitinating enzymes in protein quality control (2020)