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.

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 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
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