DUSP9

General Information

Full gene name:dual specificity phosphatase 9 Entrez Gene ID:1852 Location:Xq28 Synonyms:MKP-4, MKP4 Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs3020789	14910	upstream

NCBI Summary

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 is 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 shows selectivity for members of the ERK family of MAP kinases, is expressed only in placenta, kidney, and fetal liver, and is localized to the cytoplasm and nucleus. [provided by RefSeq, Jul 2008]

OMIM

OMIM ID:`OMIM ID 300134 `_

NCBI Phenotypes

• Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
• NHGRI GWA Catalog

Gene Ontology

• protein tyrosine phosphatase activity
• cytosol
• inactivation of MAPK activity
• endoplasmic reticulum
• phosphoprotein phosphatase activity
• cytoplasm
• MAP kinase tyrosine/serine/threonine phosphatase activity
• nucleus
• JNK cascade
• protein dephosphorylation

KEGG Pathways

• MAPK signaling pathway

GeneRIFs

• microtubule disruption by MKP4 provides a novel mechanism for tumor suppression by a cytosolic MKP [PMID 18006813]
• decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. [PMID 21943117]
• DUSP9/MKP-4 is a bona fide target of PKA signaling and attenuation of DUSP9/MKP-4 function can mediate cross-talk between the PKA pathway and MAPK signaling through both ERK1/2 and p38alpha in vivo [PMID 21908610]
• Affinity Capture-MS [PMID 21906983]
• 2.7 A resolution crystal structure of the catalytic domain of MKP-4 (MKP-4C) is presented [PMID 21206059]

PubMed Articles

Recent articles:

• Dickinson RJ et al. “Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates cross-talk between protein kinase A and MAP kinase signaling pathways.” J Biol Chem. 2011 Nov 4;286(44):38018-26. PMID 21908610
• Kim W et al. “Systematic and quantitative assessment of the ubiquitin-modified proteome.” Mol Cell. 2011 Oct 21;44(2):325-40. PMID 21906983
• Wu S et al. “Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma.” BMC Cancer. 2011 Sep 26;11:413. PMID 21943117
• Danielsen JM et al. “Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.” Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. PMID 21139048
• Jeong DG et al. “Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.” Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):25-31. PMID 21206059
• Voight BF et al. “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.” Nat Genet. 2010 Jul;42(7):579-89. PMID 20581827
• Barbe L et al. “Toward a confocal subcellular atlas of the human proteome.” Mol Cell Proteomics. 2008 Mar;7(3):499-508. PMID 18029348
• Liu Y et al. “Microtubule disruption and tumor suppression by mitogen-activated protein kinase phosphatase 4.” Cancer Res. 2007 Nov 15;67(22):10711-9. PMID 18006813
• Ross MT et al. “The DNA sequence of the human X chromosome.” Nature. 2005 Mar 17;434(7031):325-37. PMID 15772651
• Strausberg RL et al. “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.” Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903. PMID 12477932

Top Pubmed articles linked to gene DUSP9 matching any search term:

• Bao XY et al. “Replication study of novel risk variants in six genes with type 2 diabetes and related quantitative traits in the Han Chinese lean individuals.” Mol Biol Rep. 2012 Mar;39(3):2447-54. PMID 21643948
• Rees SD et al. “Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.” Diabetologia. 2011 Jun;54(6):1368-74. PMID 21350842
• Nielsen T et al. “Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release.” Diabetologia. 2011 May;54(5):1052-6. PMID 21267535
• Jeong DG et al. “Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4.” Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):25-31. PMID 21206059
• Voight BF et al. “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.” Nat Genet. 2010 Jul;42(7):579-89. PMID 20581827
• Paulson QX et al. “Effects of body weight and alcohol consumption on insulin sensitivity.” Nutr J. 2010 Mar 22;9:14. PMID 20307313
• Emanuelli B et al. “Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance.” Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3545-50. PMID 18296638
• Hong SB et al. “Expression, purification, and enzymatic characterization of the dual specificity mitogen-activated protein kinase phosphatase, MKP-4.” Bioorg Chem. 2005 Feb;33(1):34-44. PMID 15668181
• Bazuine M et al. “Mitogen-activated protein kinase (MAPK) phosphatase-1 and -4 attenuate p38 MAPK during dexamethasone-induced insulin resistance in 3T3-L1 adipocytes.” Mol Endocrinol. 2004 Jul;18(7):1697-707. PMID 15184525
• Xu H et al. “Dual specificity mitogen-activated protein (MAP) kinase phosphatase-4 plays a potential role in insulin resistance.” J Biol Chem. 2003 Aug 8;278(32):30187-92. PMID 12777378