UCHL3: Ubiquitin C-Terminal Hydrolase L3
A deubiquitinating enzyme involved in protein homeostasis, DNA repair, and cancer biology
Gene Information Card
| Symbol | UCHL3 |
|---|---|
| Full Name | Ubiquitin C-Terminal Hydrolase L3 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q22.2 |
| NCBI Gene ID | 7347 ncbi.nlm.nih.gov/gene/7347 |
| Ensembl ID | ENSG00000139618 |
| UniProt ID | P15374 |
| OMIM ID | 603090 |
| HGNC ID | 12513 |
| Aliases | UCH-L3, UCHL3P, UCHL3S |
Description
UCHL3 encodes a member of the ubiquitin C-terminal hydrolase (UCH) family of deubiquitinating enzymes. The protein cleaves ubiquitin from small adducts and plays a role in ubiquitin recycling, protein degradation, DNA damage response, and cell cycle regulation. UCHL3 is implicated in cancer, neurodegenerative diseases, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression promotes tumor growth via enhanced deubiquitination of oncogenic substrates | COSMIC, literature |
| Neurodegeneration (Alzheimer's, Parkinson's) | Altered UCHL3 activity affects proteostasis and aggregation of disease-related proteins | UniProt, literature |
| Metabolic syndrome | UCHL3 regulates insulin signaling and adipogenesis | Literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 18.5 | Medium |
| Kidney | 14.1 | Medium |
| Testis | 22.3 | High |
| Skeletal Muscle | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 20.1 | High expression |
| HeLa | 18.4 | High expression |
| HepG2 | 15.6 | Medium expression |
| K562 | 12.3 | Medium expression |
| A549 | 14.7 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.227A>G (p.Gln76Arg) | Missense | <0.01% | Unknown functional impact |
| c.463C>T (p.Arg155Cys) | Missense | <0.01% | Potential loss of deubiquitinase activity |
| c.559G>A (p.Gly187Ser) | Missense | <0.01% | Reported in cancer samples (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair catalytic cysteine (Cys95) or disrupt substrate binding reduce deubiquitinase activity.
Gain of Function (GOF)
Overexpression or activating mutations enhance deubiquitination of oncoproteins, promoting cell proliferation.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with wild-type UCHL3 dimerization.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • nucleus (GO:0005634) | • cytosol (GO:0005829) |
| • thiol-dependent ubiquitinyl hydrolase activity (GO:0036459) | • DNA damage response (GO:0006974) |
Pathways
• Ubiquitin-proteasome pathway (KEGG hsa04120)
• DNA damage response (Reactome R-HSA-73893)
• Cell cycle (Reactome R-HSA-1640170)
Protein Summary
UCHL3 is a 230-amino acid deubiquitinating enzyme with a catalytic triad (Cys95, His169, Asp184). It hydrolyzes ubiquitin from small adducts and is involved in ubiquitin homeostasis, DNA repair, and cell cycle progression. The protein is widely expressed, with highest levels in testis and brain. Dysregulation of UCHL3 is linked to cancer and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UCHL3 Knockout HEK293 Cell Line | EDJ-KQ2947 | Human | 7347 | Details Get a Quote |
| UCHL3 Knockout A-549 Cell Line | EDJ-KQ24074 | Human | 7347 | Details Get a Quote |
| UCHL3 Knockout HCT 116 Cell Line | EDJ-KQ24075 | Human | 7347 | Details Get a Quote |
| UCHL3 Knockout HeLa Cell Line | EDJ-KQ24076 | Human | 7347 | Details Get a Quote |
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