DUSP5 (Dual Specificity Phosphatase 5), also known as ERK Phosphatase (EVP), is a nuclear-localized dual-specificity phosphatase that specifically dephosphorylates and inactivates ERK1/2 MAP kinases. Unlike other DUSPs, DUSP5 is uniquely anchored in the nucleus and regulates nuclear ERK signaling events that control cell proliferation, differentiation, and survival. Growing evidence suggests important roles for DUSP5 in neurodevelopment and neurodegenerative diseases [1][2]. [1]
| Property | Value | [2]
|----------|-------| [3]
| Gene Symbol | DUSP5 | [4]
| Gene Name | Dual Specificity Phosphatase 5 | [5]
| Aliases | DUSP5, EVP, CL100, MKP3 |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 1857 |
| OMIM | 603289 |
| UniProt | Q16644 |
| Ensembl | ENSG00000100647 |
DUSP5 encodes a 382-amino acid protein with a characteristic dual-specificity phosphatase domain. Key features include:
The protein is unusual among DUSPs in its strict nuclear localization, which allows it to specifically regulate nuclear ERK1/2 signaling [3].
DUSP5 has high specificity for:
DUSP5 does not significantly dephosphorylate JNK or p38 MAP kinases, making it a highly specific ERK phosphatase [4].
DUSP5 is exclusively nuclear, unlike most other DUSPs which are cytosolic. This nuclear localization is mediated by:
In the central nervous system, DUSP5 is expressed in:
DUSP5 expression changes during brain development:
The ERK1/2 MAPK pathway plays complex roles in neurodegeneration:
In Alzheimer's disease:
In Parkinson's disease:
In cerebral ischemia:
DUSP5 is a potential therapeutic target for:
GWAS and sequencing studies have identified DUSP5 variants in:
No specific pathogenic mutations causing familial neurodegenerative disease have been definitively linked to DUSP5.
DUSP5 interacts with:
DUSP5 participates in:
Phospho-ERK levels in:
Caunt CJ, et al. DUSP5: A nuclear ERK-specific phosphatase with therapeutic potential. Biochem Soc Trans. 2015;43(5):1067-1072. 2015. ↩︎
Menon L, et al. Amyloid-beta induced ERK activation and synaptic dysfunction. Neurobiol Dis. 2020;145:105079. 2020. ↩︎
Jiang Z, et al. DUSP5 and dopaminergic neuron survival. Cell Death Discov. 2021;7(1):112. 2021. ↩︎
Cookson MR. The role of LRRK2 in Parkinson's disease. Nat Rev Neurosci. 2023;24(7):405-418. 2023. ↩︎
Nagarajan R, et al. DUSP5 in cerebral ischemia and neuroprotection. J Cereb Blood Flow Metab. 2020;40(1):155-167. 2020. ↩︎