UCHL1 (Ubiquitin C-Terminal Hydrolase L1)
A deubiquitinating enzyme with roles in neurodegeneration and cancer
Gene Information Card
| Symbol | UCHL1 |
|---|---|
| Full Name | Ubiquitin C-Terminal Hydrolase L1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p13 |
| NCBI Gene ID | 7345 ncbi.nlm.nih.gov/gene/7345 |
| Ensembl ID | ENSG00000154277 |
| UniProt ID | P09936 |
| OMIM ID | 191342 |
| HGNC ID | 12513 |
| Aliases | PGP9.5, PARK5, UCH-L1, HEL-117 |
Description
UCHL1 encodes ubiquitin C-terminal hydrolase L1, a member of the deubiquitinating enzyme family. It hydrolyzes small C-terminal adducts of ubiquitin to generate ubiquitin monomers and is involved in the processing of ubiquitin precursors and ubiquitinated proteins. The protein is highly expressed in neurons and is associated with neurodegenerative diseases such as Parkinson disease (PARK5) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease 5 (PARK5) | Missense mutation (I93M) reduces hydrolase activity and increases aggregation, leading to dopaminergic neuron loss | OMIM 191342; PMID: 12627230 |
| Hereditary sensory and autonomic neuropathy type 1C | Loss-of-function mutations impair axonal transport and ubiquitin homeostasis | OMIM 613708; PMID: 23332917 |
| Alzheimer disease | Altered UCHL1 expression and oxidative modifications contribute to tau pathology | PMID: 16983685 |
| Lung cancer | Overexpression promotes tumor growth; UCHL1 is a target of epigenetic silencing in some cancers | PMID: 21502544 |
| Breast cancer | UCHL1 expression correlates with poor prognosis; promotes metastasis via EMT | PMID: 23382210 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 44.2 | High |
| Testis | 12.5 | Medium |
| Adrenal gland | 8.3 | Medium |
| Pancreas | 3.1 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 35.6 | High expression |
| HeLa (cervical carcinoma) | 2.4 | Low expression |
| A549 (lung carcinoma) | 5.1 | Medium expression |
| MCF7 (breast carcinoma) | 1.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| I93M | Missense | Rare (familial Parkinson disease) | Reduced hydrolase activity; increased aggregation |
| E7A | Missense | Rare (neuropathy) | Loss of catalytic activity |
| S18Y | Missense | Polymorphism (population-specific) | Reduced risk for Parkinson disease; altered substrate specificity |
Mutation functional classification
Loss of Function (LOF)
E7A and other truncating mutations lead to loss of hydrolase activity and impaired ubiquitin recycling.
Gain of Function (GOF)
I93M may confer a toxic gain-of-function through increased aggregation propensity.
Dominant Negative (DN)
I93M is proposed to act via dominant-negative interference with wild-type UCHL1 dimerization.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity (GO:0036459) | • ubiquitin binding (GO:0043130) |
| • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) | • axon transport (GO:0008088) |
| • neuron projection development (GO:0031175) |
Pathways
• Ubiquitin-proteasome system (KEGG hsa04120)
• Parkinson disease (KEGG hsa05012)
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
Protein Summary
UCHL1 is a 223-amino acid protein (24.8 kDa) belonging to the ubiquitin C-terminal hydrolase family. It functions as a deubiquitinating enzyme that cleaves ubiquitin from small adducts and plays a role in ubiquitin homeostasis. The protein is predominantly expressed in neurons and neuroendocrine cells. It has been implicated in synaptic function, axonal transport, and proteasomal degradation. Mutations in UCHL1 are associated with familial Parkinson disease and hereditary sensory neuropathy. In cancer, UCHL1 can act as either an oncogene or tumor suppressor depending on context.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UCHL1 Knockout HEK293 Cell Line | EDJ-KQ5990 | Human | 7345 | Details Get a Quote |
| UCHL1 Knockout HeLa Cell Line | EDJ-KQ28301 | Human | 7345 | Details Get a Quote |
| UCHL1 Knockout A-549 Cell Line | EDC90121 | Human | 7345 | Details Get a Quote |
| UCHL1 Knockout HCT 116 Cell Line | EDJ-KQ29577 | Human | 7345 | Details Get a Quote |
