DUSP4

MKP 2, homo24mer, Human.

DUSP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3EZZ
Identifiers
Aliases	DUSP4, HVH2, MKP-2, MKP2, TYP, dual specificity phosphatase 4
External IDs	OMIM: 602747 MGI: 2442191 HomoloGene: 1065 GeneCards: DUSP4
Gene location (Human) Chr. Chromosome 8 (human) Band 8p12 Start 29,333,064 bp End 29,350,684 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 A4 Start 35,274,451 bp End 35,287,048 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium lactiferous duct seminal vesicula palpebral conjunctiva sperm trachea mucosa of urinary bladder nipple body of pancreas bronchial epithelial cell Top expressed in ganglionic eminence neural tube white adipose tissue mesencephalon spermatid spinal cord yolk sac rhombencephalon hippocampus proper respiratory epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphoprotein phosphatase activity MAP kinase tyrosine/serine/threonine phosphatase activity hydrolase activity protein tyrosine/serine/threonine phosphatase activity protein tyrosine/threonine phosphatase activity phosphatase activity protein tyrosine phosphatase activity MAP kinase serine/threonine phosphatase activity protein binding Cellular component nucleoplasm nucleus cytoplasm Biological process endoderm formation protein dephosphorylation peptidyl-threonine dephosphorylation dephosphorylation peptidyl-tyrosine dephosphorylation negative regulation of ERK1 and ERK2 cascade Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1846 319520 Ensembl ENSG00000120875 ENSMUSG00000031530 UniProt Q13115 Q8BFV3 RefSeq (mRNA) NM_001394 NM_057158 NM_176933 RefSeq (protein) NP_001385 NP_476499 NP_795907 Location (UCSC) Chr 8: 29.33 – 29.35 Mb Chr 8: 35.27 – 35.29 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.

Function

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported.

In melanocytic cells DUSP4 gene expression may be regulated by MITF.

Further reading

• King AG, Ozanne BW, Smythe C, Ashworth A (Dec 1995). "Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk". Oncogene. 11 (12): 2553–63. PMID 8545112.
• Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K (Mar 1996). "The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation". The Journal of Biological Chemistry. 271 (11): 6497–501. doi:10.1074/jbc.271.11.6497. PMID 8626452.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (Jul 2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nature Neuroscience. 3 (7): 661–9. doi:10.1038/76615. hdl:1842/742. PMID 10862698. S2CID 14392630.
• Chen P, Hutter D, Yang X, Gorospe M, Davis RJ, Liu Y (Aug 2001). "Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically". The Journal of Biological Chemistry. 276 (31): 29440–9. doi:10.1074/jbc.M103463200. PMID 11387337.
• Cadalbert L, Sloss CM, Cameron P, Plevin R (Oct 2005). "Conditional expression of MAP kinase phosphatase-2 protects against genotoxic stress-induced apoptosis by binding and selective dephosphorylation of nuclear activated c-jun N-terminal kinase". Cellular Signalling. 17 (10): 1254–64. doi:10.1016/j.cellsig.2005.01.003. PMID 16038800.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Tresini M, Lorenzini A, Torres C, Cristofalo VJ (Feb 2007). "Modulation of replicative senescence of diploid human cells by nuclear ERK signaling". The Journal of Biological Chemistry. 282 (6): 4136–51. doi:10.1074/jbc.M604955200. PMID 17145763.
• Wang J, Shen WH, Jin YJ, Brandt-Rauf PW, Yin Y (Jun 2007). "A molecular link between E2F-1 and the MAPK cascade". The Journal of Biological Chemistry. 282 (25): 18521–31. doi:10.1074/jbc.M610538200. PMID 17452331.

External links

• Overview of all the structural information available in the PDB for UniProt: Q13115 (Human Dual specificity protein phosphatase 4) at the PDBe-KB.