DUSP8: Dual Specificity Phosphatase 8

A key regulator of MAPK signaling and stress response pathways

Gene Information Card

Symbol DUSP8
Full Name Dual Specificity Phosphatase 8
Gene Type Protein coding
Chromosomal Location 11p15.4
NCBI Gene ID 1850 ncbi.nlm.nih.gov/gene/1850
Ensembl ID ENSG00000120885
UniProt ID Q13202
OMIM ID 602803
HGNC ID 3070
Aliases C11orf81, DUSP8, HVH5, MKP-3, VH5

Description

DUSP8 (Dual Specificity Phosphatase 8) encodes a member of the dual specificity protein phosphatase subfamily. This protein inactivates mitogen-activated protein (MAP) kinases by dephosphorylating both threonine and tyrosine residues. DUSP8 specifically dephosphorylates ERK, JNK, and p38 MAP kinases, thereby negatively regulating MAPK signaling pathways involved in cell proliferation, differentiation, and stress responses. It is widely expressed in various tissues, with high levels in the brain, heart, and skeletal muscle.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Type 2 diabetes DUSP8 variants may alter MAPK signaling in insulin-responsive tissues, contributing to insulin resistance GWAS studies (PMID: 24509480)
Obesity DUSP8 expression changes in adipose tissue affect energy metabolism and adipogenesis Association studies (PMID: 25664854)
Cancer (various) Dysregulation of DUSP8 can lead to aberrant MAPK signaling, promoting tumorigenesis COSMIC mutation data

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.5 High
Heart 9.8 Medium
Skeletal Muscle 8.2 Medium
Liver 3.1 Low
Pancreas 2.5 Low
Cell Line Expression
Cell Line nTPM Notes
HEK 293 15.2 High expression
HeLa 8.7 Moderate expression
MCF7 5.3 Low expression
HepG2 4.1 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.497C>T (p.Thr166Met) Missense 0.02% (gnomAD) May reduce phosphatase activity
c.1045G>A (p.Gly349Ser) Missense 0.01% (gnomAD) Unknown functional effect
c.1234_1235insA Frameshift Rare Likely loss of function
Mutation functional classification

Loss of Function (LOF)

Frameshift and nonsense mutations that truncate the protein or disrupt the catalytic domain are predicted to cause loss of function.

Gain of Function (GOF)

No confirmed gain-of-function mutations reported.

Dominant Negative (DN)

No dominant-negative mutations described.

Gene Ontology (GO)

• MAP kinase phosphatase activity • protein tyrosine phosphatase activity
• protein serine/threonine phosphatase activity • negative regulation of MAPK cascade
• JNK cascade • ERK1 and ERK2 cascade
• p38MAPK cascade • dephosphorylation

Pathways

• MAPK signaling pathway (KEGG: hsa04010)
• Negative regulation of MAPK signaling (Reactome: R-HSA-5673001)

Protein Summary

DUSP8 is a 55 kDa protein (393 amino acids) that contains a dual specificity phosphatase catalytic domain. It localizes to the cytoplasm and nucleus. The protein binds to and dephosphorylates MAP kinases (ERK, JNK, p38) with high specificity, thereby terminating MAPK signaling. DUSP8 is regulated at the transcriptional level by stress stimuli and growth factors. Its expression is altered in several disease states, including metabolic disorders and cancer.

Related Products

Product name Cat.No. Species Gene ID
DUSP8 Knockout HEK293 Cell Line EDJ-KQ647 Human 1850 Details Get a Quote
DUSP8 Knockout A-549 Cell Line EDJ-KQ19135 Human 1850 Details Get a Quote
DUSP8 Knockout HCT 116 Cell Line EDJ-KQ19136 Human 1850 Details Get a Quote
DUSP8 Knockout HeLa Cell Line EDJ-KQ19137 Human 1850 Details Get a Quote
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