DUSP3 (Dual Specificity Phosphatase 3)
A key regulator of cell signaling, proliferation, and immune response
Gene Information Card
| Symbol | DUSP3 |
|---|---|
| Full Name | Dual Specificity Phosphatase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.1 |
| NCBI Gene ID | 1845 ncbi.nlm.nih.gov/gene/1845 |
| Ensembl ID | ENSG00000108861 |
| UniProt ID | P51452 |
| OMIM ID | 600183 |
| HGNC ID | 3071 |
| Aliases | VHR, T-DSP11 |
Description
DUSP3 (dual specificity phosphatase 3), also known as VHR (vaccinia H1-related phosphatase), is a member of the dual specificity protein phosphatase subfamily. It dephosphorylates phosphotyrosine and phosphoserine/threonine residues within the same substrate, primarily targeting MAP kinases (ERK1/2, JNK, p38) and STAT5. DUSP3 plays critical roles in cell cycle progression, DNA damage response, angiogenesis, and immune regulation. Its dysregulation is implicated in various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | DUSP3 overexpression promotes cell proliferation and invasion via sustained ERK signaling | PMID: 25605274 |
| Prostate cancer | Loss of DUSP3 enhances JNK-mediated apoptosis and reduces tumor growth | PMID: 21317922 |
| Colorectal cancer | DUSP3 upregulation correlates with poor prognosis and chemoresistance | PMID: 29187729 |
| Inflammatory bowel disease | DUSP3 deficiency exacerbates colitis through increased p38 and JNK activity | PMID: 26921325 |
| Viral infection | DUSP3 modulates host antiviral response by dephosphorylating STAT5 | PMID: 23408620 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Lung | 6.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | Medium expression |
| MCF7 | 9.8 | Medium expression |
| A549 | 7.3 | Low expression |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148G>A (p.Glu50Lys) | Missense | <0.01% | Reduced phosphatase activity |
| c.205C>T (p.Arg69Trp) | Missense | <0.01% | Impaired substrate binding |
| c.334_336del (p.Lys112del) | In-frame deletion | <0.01% | Altered protein stability |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Glu50Lys) reduce catalytic activity, impairing MAPK dephosphorylation and leading to sustained signaling.
Gain of Function (GOF)
Not well documented; overexpression in cancers suggests potential gain-of-function through increased protein levels.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data:
Gene Ontology (GO)
| • Protein tyrosine phosphatase activity | • MAP kinase phosphatase activity |
| • Protein dephosphorylation | • Cell cycle regulation |
| • DNA damage response | • Angiogenesis |
Pathways
• MAPK signaling pathway
• JNK cascade
• p38 MAPK pathway
• ErbB signaling pathway
• FoxO signaling pathway
Protein Summary
DUSP3 encodes a 185-amino acid dual specificity phosphatase (VHR) that contains a conserved active site motif (HCxxGxxRS/T). It preferentially dephosphorylates phosphotyrosine and phosphothreonine residues in MAP kinases (ERK1/2, JNK, p38) and STAT5. VHR is localized in the nucleus and cytoplasm, and its activity is regulated by phosphorylation and redox status. It is essential for cell cycle progression at G1/S transition and for proper DNA damage checkpoint control.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DUSP3 Knockout HEK293 Cell Line | EDJ-KQ643 | Human | 1845 | Details Get a Quote |
| DUSP3 Knockout A-549 Cell Line | EDJ-KQ19123 | Human | 1845 | Details Get a Quote |
| DUSP3 Knockout HCT 116 Cell Line | EDJ-KQ19124 | Human | 1845 | Details Get a Quote |
| DUSP3 Knockout HeLa Cell Line | EDJ-KQ19125 | Human | 1845 | Details Get a Quote |