USP14: Ubiquitin Specific Peptidase 14
A deubiquitinating enzyme regulating proteasome function and protein degradation
Gene Information Card
| Symbol | USP14 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 18p11.32 |
| NCBI Gene ID | 9097 ncbi.nlm.nih.gov/gene/9097 |
| Ensembl ID | ENSG00000101557 |
| UniProt ID | P54578 |
| OMIM ID | 607274 |
| HGNC ID | 12612 |
| Aliases | TGT, UBP14, USP14L |
Description
USP14 encodes a deubiquitinating enzyme that is a component of the proteasome complex. It removes ubiquitin chains from substrates prior to degradation, regulating proteasomal activity and protein turnover. USP14 is involved in synaptic development, neurodegeneration, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's, Parkinson's) | Impaired deubiquitination leads to accumulation of toxic proteins and proteasome dysfunction | PMID: 25730884; ClinVar |
| Cancer (multiple types) | USP14 overexpression promotes tumor growth by stabilizing oncoproteins; loss of function may impair DNA repair | PMID: 29533785; COSMIC |
| Autism spectrum disorder | USP14 variants affect synaptic protein turnover and neuronal connectivity | PMID: 27545674; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Heart | 5.4 | Medium |
| Kidney | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| HeLa | 8.7 | Medium expression |
| SH-SY5Y | 9.1 | High expression |
| MCF7 | 7.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118A>G (p.Thr40Ala) | Missense | 0.001% | Reduced deubiquitinase activity |
| c.512C>T (p.Pro171Leu) | Missense | 0.002% | Altered proteasome binding |
| c.1000_1002del (p.Lys334del) | Deletion | <0.001% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and deletion variants that reduce or abolish catalytic activity, impairing ubiquitin chain removal and proteasomal degradation.
Gain of Function (GOF)
Not well characterized; some variants may increase activity, but evidence is limited.
Dominant Negative (DN)
Certain mutations may interfere with proteasome complex assembly, exerting a dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-dependent protein catabolic process (GO:0006511) | • cysteine-type peptidase activity (GO:0008234) |
| • thiol-dependent ubiquitinyl hydrolase activity (GO:0036459) | • proteasome complex (GO:0000502) |
| • cytoplasm (GO:0005737) | • nucleus (GO:0005634) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Proteasome (KEGG: hsa03050)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
USP14 is a 494-amino acid deubiquitinating enzyme (DUB) that associates with the 19S regulatory particle of the proteasome. It trims ubiquitin chains from substrates, regulating their degradation rate. The protein contains a catalytic cysteine (Cys114) and a ubiquitin-binding domain. USP14 is essential for synaptic function and neuronal survival; dysregulation contributes to neurodegeneration and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP14 Knockout HEK293 Cell Line | EDJ-KQ16048 | Human | 9097 | Details Get a Quote |
| USP14 Knockout HCT 116 Cell Line | EDJ-KQ45950 | Human | 9097 | Details Get a Quote |
| USP14 Knockout A-549 Cell Line | EDJ-KQ47173 | Human | 9097 | Details Get a Quote |
| USP14 Knockout HeLa Cell Line | EDJ-KQ47175 | Human | 9097 | Details Get a Quote |
