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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DUSP5
dual specificity phosphatase 5
Chromosome 10 · 10q25.2
NCBI Gene: 1847Ensembl: ENSG00000138166.7HGNC: HGNC:3071UniProt: Q16690
59PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
dephosphorylationpeptidyl-tyrosine dephosphorylationpeptidyl-threonine dephosphorylationprotein bindingCrohn's diseaseinflammatory bowel diseaselymphatic system diseasecardiac transplant
✦AI Summary

DUSP5 (dual specificity phosphatase 5) is a dual-specificity protein phosphatase that dephosphorylates both serine/threonine and tyrosine residues, with highest activity toward ERK1 1. The enzyme functions as a negative regulator of MAPK signaling pathways, particularly the ERK1/2 cascade, by dephosphorylating and inactivating these kinases 23. DUSP5 expression is regulated by post-translational modifications, with ubiquitination leading to its degradation 4. The protein demonstrates context-dependent roles in disease pathogenesis. In cancer, DUSP5 is upregulated in lung adenocarcinoma, particularly in KRAS-mutant tumors, where it promotes cell proliferation and poor survival outcomes 5. Conversely, DUSP5 exhibits protective functions in inflammatory conditions: it suppresses IL-1β-induced chondrocyte inflammation in osteoarthritis by inhibiting NF-κB and ERK pathways 3, and its knockdown in acute kidney injury enhances autophagy through AMPK/ULK1 signaling, reducing inflammation and apoptosis 6. In chr10 prostatitis, epithelial cell-derived exosomal miR-203a-3p targets DUSP5, promoting stromal inflammation via ERK1/2/MCP-1 signaling 2. DUSP5 represents a potential therapeutic target, with its modulation showing promise in treating various pathological conditions including autoimmune diseases and cancer 7.

Sources cited
1
DUSP5 has highest relative activity toward ERK1 and is involved in MAPK/ERK signaling regulation
PMID: 35715841
2
DUSP5 is targeted by miR-203a-3p and regulates stromal inflammation through ERK1/2/MCP-1 signaling pathway
PMID: 38724995
3
DUSP5 suppresses IL-1β-induced chondrocyte inflammation by inhibiting NF-κB and ERK pathways
PMID: 33361528
4
DUSP5 undergoes ubiquitination-induced degradation as a regulatory mechanism
PMID: 31151270
5
DUSP5 is upregulated in lung adenocarcinoma, particularly in KRAS-mutant tumors, and promotes cell proliferation
PMID: 40939510
6
DUSP5 knockdown in acute kidney injury enhances autophagy through AMPK/ULK1 pathway, reducing inflammation
PMID: 39218057
7
DUSP5 is involved in T-cell activation and represents a potential therapeutic target for autoimmune diseases
PMID: 31766293
Disease Associationsⓘ20
Crohn's diseaseOpen Targets
0.43Moderate
inflammatory bowel diseaseOpen Targets
0.37Weak
lymphatic system diseaseOpen Targets
0.36Weak
cardiac transplantOpen Targets
0.31Weak
vein disorderOpen Targets
0.30Weak
response to antibioticOpen Targets
0.30Weak
response to xenobiotic stimulusOpen Targets
0.30Weak
poisoningOpen Targets
0.29Weak
frozen shoulderOpen Targets
0.24Weak
colorectal carcinomaOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.07Suggestive
thyroid cancer, nonmedullary, 2Open Targets
0.06Suggestive
immunodeficiency 18Open Targets
0.06Suggestive
reticular dysgenesisOpen Targets
0.06Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.06Suggestive
placenta praeviaOpen Targets
0.06Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MAPK14Protein interaction100%FOSProtein interaction96%MAPK3Protein interaction94%MAPK9Protein interaction94%MAPK12Protein interaction92%MAPK8Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
23%
Lung
20%
Liver
19%
Ovary
5%
Brain
5%
Gene Interaction Network
Click a node to explore
DUSP5MAPK14FOSMAPK3MAPK9MAPK12MAPK8
PROTEIN STRUCTURE
Preparing viewer…
PDB2G6Z · 2.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.53–1.07]
RankingsWhere DUSP5 stands among ~20K protein-coding genes
  • #7,764of 20,598
    Most Researched59
  • #10,787of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedDUSP5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling.
PMID: 35715841
Stem Cell Res Ther · 2022
1.00
2
Multiple functions of autophagy in vascular calcification.
PMID: 34399835
Cell Biosci · 2021
0.90
3
DUSP5 deficiency suppresses the progression of acute kidney injury by enhancing autophagy through AMPK/ULK1 pathway.
PMID: 39218057
Transl Res · 2024
0.80
4
MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus.
PMID: 31766293
Cells · 2019
0.70
5
Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability.
PMID: 31151270
Int J Mol Sci · 2019
0.60