DUSP4 (Dual Specificity Phosphatase 4)
A key regulator of MAPK signaling and tumor suppression
Gene Information Card
| Symbol | DUSP4 |
|---|---|
| Full Name | Dual Specificity Phosphatase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p12-p11.21 |
| NCBI Gene ID | 1846 ncbi.nlm.nih.gov/gene/1846 |
| Ensembl ID | ENSG00000120875 |
| UniProt ID | Q13115 |
| OMIM ID | 602747 |
| HGNC ID | 3070 |
| Aliases | MKP-2, MKP2, HVH2, TYP |
Description
DUSP4 encodes a dual specificity phosphatase that dephosphorylates phosphotyrosine and phosphothreonine residues within MAP kinases, particularly ERK1/2 and JNK. It acts as a negative regulator of MAPK signaling, modulating cell proliferation, differentiation, and apoptosis. DUSP4 is frequently downregulated or mutated in various cancers, suggesting a tumor suppressor role.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of DUSP4 expression leads to sustained ERK signaling and increased proliferation | PMID: 22926558 |
| Colorectal cancer | DUSP4 inactivation via promoter methylation or mutation enhances MAPK pathway activity | PMID: 24803657 |
| Lung adenocarcinoma | Reduced DUSP4 correlates with poor prognosis and KRAS-driven tumor progression | PMID: 27197191 |
| Pancreatic cancer | DUSP4 loss promotes KRAS-mediated tumorigenesis | PMID: 27626311 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Lung | 8.5 | Low |
| Breast | 6.3 | Low |
| Colon | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 4.2 | Moderate expression |
| A549 (lung cancer) | 2.1 | Low expression |
| HCT116 (colorectal cancer) | 3.8 | Low expression |
| HEK293 (embryonic kidney) | 7.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511C>T (p.Arg171*) | Nonsense | <1% | Loss of function; truncated protein |
| c.832G>A (p.Glu278Lys) | Missense | <0.5% | Unknown; predicted damaging |
| c.1045_1046del (p.Glu349fs) | Frameshift | <0.1% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent DUSP4 protein, impairing MAPK dephosphorylation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not described for DUSP4.
View complete mutation data：
Gene Ontology (GO)
| • MAP kinase phosphatase activity | • protein tyrosine phosphatase activity |
| • protein serine/threonine phosphatase activity | • negative regulation of ERK1 and ERK2 cascade |
| • inactivation of MAPK activity | • cellular response to growth factor stimulus |
Pathways
• MAPK signaling pathway (Reactome: R-HSA-5673001)
• Negative regulation of MAPK pathway (KEGG: hsa04010)
• ERK signaling (WikiPathways: WP382)
Protein Summary
DUSP4 (MKP-2) is a 394-amino acid protein containing a N-terminal rhodanese-like domain and a C-terminal dual specificity phosphatase domain. It specifically dephosphorylates phosphothreonine and phosphotyrosine residues on MAP kinases, with highest activity toward ERK1/2 and JNK. The protein localizes to the nucleus and is induced by growth factors and stress signals, forming a negative feedback loop to control MAPK output.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DUSP4 Knockout HEK293 Cell Line | EDJ-KQ644 | Human | 1846 | Details Get a Quote |
| DUSP4 Knockout A-549 Cell Line | EDJ-KQ18068 | Human | 1846 | Details Get a Quote |
| DUSP4 Knockout HCT 116 Cell Line | EDJ-KQ19127 | Human | 1846 | Details Get a Quote |
| DUSP4 Knockout HeLa Cell Line | EDJ-KQ19128 | Human | 1846 | Details Get a Quote |
