USP4: Ubiquitin Specific Peptidase 4
A deubiquitinating enzyme involved in TGF-β signaling, p53 regulation, and cancer progression.
Gene Information Card
| Symbol | USP4 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 7375 ncbi.nlm.nih.gov/gene/7375 |
| Ensembl ID | ENSG00000114316 |
| UniProt ID | Q13107 |
| OMIM ID | 603486 |
| HGNC ID | 12627 |
| Aliases | UNP, UNPH |
Description
USP4 (Ubiquitin Specific Peptidase 4) encodes a deubiquitinating enzyme that removes ubiquitin from specific protein substrates, thereby regulating protein stability, localization, and activity. It plays key roles in TGF-β signaling, p53/TP53 regulation, and NF-κB pathway modulation. USP4 is implicated in various cancers and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | USP4 overexpression stabilizes β-catenin and promotes EMT | PMID: 25605249 |
| Colorectal cancer | USP4 deubiquitinates and stabilizes β-catenin, enhancing Wnt signaling | PMID: 23376921 |
| Hepatocellular carcinoma | USP4 upregulation correlates with poor prognosis; promotes cell proliferation | PMID: 29065170 |
| Lung cancer | USP4 deubiquitinates and stabilizes p53, affecting apoptosis | PMID: 21572392 |
| Alzheimer disease | USP4 regulates tau protein turnover via deubiquitination | PMID: 28283569 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 15.7 | Medium |
| Lung | 9.1 | Low |
| Kidney | 11.2 | Medium |
| Testis | 22.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | Embryonic kidney |
| HeLa | 14.2 | Cervical carcinoma |
| A549 | 10.8 | Lung carcinoma |
| MCF7 | 16.1 | Breast carcinoma |
| HepG2 | 12.3 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123G>A (p.Gly375Arg) | Missense | <0.01% | Unknown functional impact |
| c.1567C>T (p.Arg523Trp) | Missense | <0.01% | Reported in COSMIC; potential loss of function |
| c.2041_2042insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of deubiquitinase activity.
Gain of Function (GOF)
Missense mutations in the catalytic domain may enhance substrate binding or activity, but evidence is limited.
Dominant Negative (DN)
No dominant-negative mutations have been reported for USP4.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
| • protein deubiquitination (GO:0016579) | • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) |
Pathways
• TGF-beta signaling pathway (Reactome: R-HSA-2173789)
• p53 signaling pathway (Reactome: R-HSA-5633007)
• NF-kappaB signaling pathway (Reactome: R-HSA-9758274)
• Wnt signaling pathway (Reactome: R-HSA-195721)
Protein Summary
USP4 is a 963-amino acid deubiquitinating enzyme containing a DUSP (domain in ubiquitin-specific proteases) and a catalytic USP domain. It removes ubiquitin chains from substrates such as β-catenin, p53, and TGF-β receptor type I, thereby modulating signaling pathways critical for cell proliferation, differentiation, and apoptosis. USP4 is overexpressed in several cancers and is considered a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP4 Knockout HEK293 Cell Line | EDJ-KQ1097 | Human | 7375 | Details Get a Quote |
| USP42 Knockout HEK293 Cell Line | EDJ-KQ2253 | Human | 84132 | Details Get a Quote |
| USP48 Knockout HEK293 Cell Line | EDJ-KQ3276 | Human | 84196 | Details Get a Quote |
| USP43 Knockout HEK293 Cell Line | EDJ-KQ7887 | Human | 124739 | Details Get a Quote |
| USP44 Knockout HEK293 Cell Line | EDJ-KQ9980 | Human | 84101 | Details Get a Quote |
| USP45 Knockout HEK293 Cell Line | EDJ-KQ10306 | Human | 85015 | Details Get a Quote |
| USP40 Knockout HEK293 Cell Line | EDJ-KQ16080 | Human | 55230 | Details Get a Quote |
| USP46 Knockout HEK293 Cell Line | EDJ-KQ16082 | Human | 64854 | Details Get a Quote |
| USP47 Knockout HEK293 Cell Line | EDJ-KQ16083 | Human | 55031 | Details Get a Quote |
| USP40 Knockout A-549 Cell Line | EDJ-KQ45990 | Human | 55230 | Details Get a Quote |
| USP46 Knockout HeLa Cell Line | EDJ-KQ45997 | Human | 64854 | Details Get a Quote |
| USP40 Knockout HCT 116 Cell Line | EDJ-KQ47214 | Human | 55230 | Details Get a Quote |
| USP40 Knockout HeLa Cell Line | EDJ-KQ47215 | Human | 55230 | Details Get a Quote |
| USP4 Knockout A-549 Cell Line | EDJ-KQ20267 | Human | 7375 | Details Get a Quote |
| USP4 Knockout HCT 116 Cell Line | EDJ-KQ20268 | Human | 7375 | Details Get a Quote |
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