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.
View complete mutation data:
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 Services
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 |