USP15: Ubiquitin Specific Peptidase 15
A deubiquitinating enzyme involved in TGF-β signaling, immune regulation, and cancer progression.
Gene Information Card
| Symbol | USP15 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 15 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q14.1 |
| NCBI Gene ID | 9958 ncbi.nlm.nih.gov/gene/9958 |
| Ensembl ID | ENSG00000135679 |
| UniProt ID | Q9Y4E8 |
| OMIM ID | 604731 |
| HGNC ID | 12614 |
| Aliases | KIAA0529, UNPH-2, UNPH4, USP15 |
Description
USP15 (Ubiquitin Specific Peptidase 15) is a deubiquitinating enzyme (DUB) that removes ubiquitin from specific target proteins, thereby regulating protein stability, localization, and activity. It plays critical roles in TGF-β signaling, NF-κB pathway modulation, and immune responses. USP15 is implicated in various cancers, neurodegenerative diseases, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | USP15 overexpression stabilizes MDM2, promoting p53 degradation and tumor growth | PMID: 24743339 |
| Glioblastoma | USP15 deubiquitinates and stabilizes the TGF-β receptor, enhancing oncogenic signaling | PMID: 22810586 |
| Ovarian cancer | USP15 amplification leads to increased deubiquitinase activity and chemoresistance | PMID: 25605248 |
| Parkinson's disease | USP15 regulates the stability of parkin and other mitophagy-related proteins | PMID: 25921536 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.7 | Low |
| Liver | 15.2 | Medium |
| Lung | 10.1 | Medium |
| Kidney | 14.5 | Medium |
| Testis | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 16.4 | High expression |
| HeLa | 12.1 | Medium expression |
| MCF7 | 9.8 | Medium expression |
| U2OS | 11.3 | Medium expression |
| SH-SY5Y | 14.7 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.01% | Unknown functional effect |
| c.567_568insA (p.Glu190Argfs*5) | Frameshift | <0.01% | Predicted loss of function |
| c.890A>G (p.Asn297Ser) | Missense | <0.01% | Reported in COSMIC as somatic in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of deubiquitinase activity.
Gain of Function (GOF)
Amplification or overexpression of USP15 in cancers is associated with gain-of-function effects, stabilizing oncogenic substrates.
Dominant Negative (DN)
No dominant-negative mutations have been characterized in USP15.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • transforming growth factor beta receptor signaling pathway (GO:0007179) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) |
Pathways
• TGF-beta signaling pathway (Reactome: R-HSA-170834)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• NF-kappaB signaling (Reactome: R-HSA-9758274)
Protein Summary
USP15 is a 981-amino acid deubiquitinating enzyme belonging to the ubiquitin-specific protease (USP) family. It contains a conserved catalytic domain and interacts with various substrates including MDM2, SMAD7, and the TGF-β receptor. USP15 regulates protein stability and signaling pathways critical for cell proliferation, differentiation, and immune responses. Its dysregulation is linked to cancer and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP15 Knockout HEK293 Cell Line | EDJ-KQ2671 | Human | 9958 | Details Get a Quote |
| DUSP15 Knockout HEK293 Cell Line | EDJ-KQ9199 | Human | 128853 | Details Get a Quote |
| USP15 Knockout A-549 Cell Line | EDJ-KQ23461 | Human | 9958 | Details Get a Quote |
| USP15 Knockout HCT 116 Cell Line | EDJ-KQ23462 | Human | 9958 | Details Get a Quote |
| USP15 Knockout HeLa Cell Line | EDJ-KQ23463 | Human | 9958 | Details Get a Quote |
| DUSP15 Knockout HeLa Cell Line | EDJ-KQ58252 | Human | 128853 | Details Get a Quote |
| DUSP15 Knockout A-549 Cell Line | EDJ-KQ66740 | Human | 128853 | Details Get a Quote |
| DUSP15 Knockout HCT 116 Cell Line | EDJ-KQ75151 | Human | 128853 | Details Get a Quote |
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