DUSP6
Dual Specificity Phosphatase 6
Gene Information Card
| Symbol | DUSP6 |
|---|---|
| Full Name | dual specificity phosphatase 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q21.33 |
| NCBI Gene ID | 1848 ncbi.nlm.nih.gov/gene/1848 |
| Ensembl ID | ENSG00000139318 |
| UniProt ID | Q16828 |
| OMIM ID | 602748 |
| HGNC ID | 3072 |
| Aliases | MKP-3, PYST1, HH19 |
Description
DUSP6 (dual specificity phosphatase 6) encodes a member of the dual specificity protein phosphatase subfamily. This protein inactivates MAP kinases, specifically ERK1 and ERK2, by dephosphorylating both phosphothreonine and phosphotyrosine residues. DUSP6 is predominantly cytoplasmic and acts as a negative regulator of the MAPK/ERK signaling pathway. It is involved in development, cell proliferation, and differentiation. Mutations and altered expression of DUSP6 have been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypogonadotropic Hypogonadism 19 with or without Anosmia (HH19) | Loss-of-function mutations in DUSP6 impair negative regulation of FGFR1 signaling, leading to disrupted GnRH neuron development. | ClinVar, OMIM |
| Non-small cell lung cancer | Reduced DUSP6 expression or promoter hypermethylation leads to sustained ERK activation, promoting tumor growth. | COSMIC, NCBI |
| Pancreatic cancer | DUSP6 is frequently downregulated, contributing to aberrant MAPK signaling and poor prognosis. | COSMIC, PubMed |
| Breast cancer | Altered DUSP6 expression correlates with ERK pathway activity and tumor progression. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 14.2 | Medium |
| Liver | 8.5 | Low |
| Lung | 11.3 | Medium |
| Pancreas | 6.1 | Low |
| Brain | 9.8 | Low |
| Kidney | 12.7 | Medium |
| Testis | 18.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| A549 | 10.8 | Lung cancer cell line |
| MCF7 | 7.3 | Breast cancer cell line |
| HEK293 | 12.1 | Embryonic kidney cell line |
| HepG2 | 9.5 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.404C>T (p.Pro135Leu) | Missense | Rare | Loss of phosphatase activity; associated with HH19 |
| c.788G>A (p.Arg263Gln) | Missense | Rare | Reduced ERK binding; associated with HH19 |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of protein expression; associated with HH19 |
| c.1063C>T (p.Arg355*) | Nonsense | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations in DUSP6 (e.g., p.Pro135Leu, p.Arg263Gln, p.Arg355*) reduce or abolish phosphatase activity, leading to sustained ERK signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in DUSP6.
Dominant Negative (DN)
No dominant-negative mutations reported in DUSP6.
View complete mutation data：
Gene Ontology (GO)
| • MAP kinase phosphatase activity | • protein tyrosine phosphatase activity |
| • protein serine/threonine phosphatase activity | • ERK1/ERK2 cascade |
| • negative regulation of MAPK cascade | • cytoplasm |
| • nucleus |
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• FGFR signaling pathway
• ERK signaling
• Negative regulation of ERK1/ERK2 cascade
Protein Summary
DUSP6 (MKP-3) is a 381-amino acid dual-specificity phosphatase that specifically dephosphorylates and inactivates ERK1 and ERK2. It contains an N-terminal ERK-binding domain and a C-terminal catalytic phosphatase domain. The protein is localized in the cytoplasm and is induced by growth factors. DUSP6 plays a critical role in feedback regulation of the MAPK pathway. Loss of DUSP6 function leads to hyperactivation of ERK signaling, contributing to developmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DUSP6 Knockout HEK293 Cell Line | EDJ-KQ646 | Human | 1848 | Details Get a Quote |
| DUSP6 Knockout HCT 116 Cell Line | EDJ-KQ18074 | Human | 1848 | Details Get a Quote |
| DUSP6 Knockout A-549 Cell Line | EDJ-KQ19132 | Human | 1848 | Details Get a Quote |
| DUSP6 Knockout HeLa Cell Line | EDJ-KQ19134 | Human | 1848 | Details Get a Quote |
