DUSP6

Dual specificity phosphatase 6
PDB rendering based on 1hzm.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HZM​, 1MKP​
Identifiers
Symbols	DUSP6 ; HH19; MKP3; PYST1
External IDs	OMIM: 602748 MGI: 1914853 HomoloGene: 55621 ChEMBL: 1250381 GeneCards: DUSP6 Gene
EC number	3.1.3.16, 3.1.3.48
Gene ontology Molecular function • protein tyrosine phosphatase activity • MAP kinase tyrosine/serine/threonine phosphatase activity Cellular component • nucleoplasm • cytoplasm • cytosol Biological process • inactivation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • dorsal/ventral pattern formation • response to organic cyclic compound • cell differentiation • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • peptidyl-tyrosine dephosphorylation • TRIF-dependent toll-like receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • regulation of fibroblast growth factor receptor signaling pathway • response to drug • regulation of endodermal cell fate specification • positive regulation of apoptotic process • innate immune response • neurotrophin TRK receptor signaling pathway • stress-activated MAPK cascade • response to nitrosative stress • regulation of heart growth • negative regulation of ERK1 and ERK2 cascade Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1848	67603
Ensembl	ENSG00000139318	ENSMUSG00000019960
UniProt	Q16828	Q9DBB1
RefSeq (mRNA)	NM_001946	NM_026268
RefSeq (protein)	NP_001937	NP_080544
Location (UCSC)	Chr 12: 89.35 – 89.35 Mb	Chr 10: 99.26 – 99.27 Mb
PubMed search

Dual specificity phosphatase 6, also known as DUSP6, is an enzyme that in humans is encoded by the DUSP6 gene.^[1][2][3]

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 ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas and, unlike most other members of this family, is localized in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene.^[1] Upregulation of spinal MKP-3 has been shown to alleviate chronic postoperative pain.^[4]

Interactions

DUSP6 has been shown to interact with MAPK3.^[5]

References

1. "Entrez Gene: DUSP6 dual specificity phosphatase 6".
2. Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S (Feb 1996). "MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". The Journal of Biological Chemistry 271 (8): 4319–26. doi:10.1074/jbc.271.8.4319. PMID 8626780.
3. Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A (Jun 1997). "Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7)". Genomics 42 (3): 524–7. doi:10.1006/geno.1997.4756. PMID 9205128.
4. Saha M, Skopelja S, Martinez E, Alvarez DL, Liponis BS, Romero-Sandoval EA (Oct 2013). "Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain". The Journal of Neuroscience 33 (43): 17182–7. doi:10.1523/JNEUROSCI.5605-12.2013. PMID 24155322.
5. Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (Apr 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". The Journal of Biological Chemistry 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID 9535927.

Further reading

• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S (Feb 1996). "MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". The Journal of Biological Chemistry 271 (8): 4319–26. doi:10.1074/jbc.271.8.4319. PMID 8626780.
• Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM (Jul 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase". The EMBO Journal 15 (14): 3621–32. PMC 451978. PMID 8670865.
• Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A (Jun 1997). "Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7)". Genomics 42 (3): 524–7. doi:10.1006/geno.1997.4756. PMID 9205128.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (Apr 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". The Journal of Biological Chemistry 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID 9535927.
• Furukawa T, Yatsuoka T, Youssef EM, Abe T, Yokoyama T, Fukushige S, Soeda E, Hoshi M, Hayashi Y, Sunamura M, Kobari M, Horii A (1999). "Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenetics and Cell Genetics 82 (3-4): 156–9. doi:10.1159/000015091. PMID 9858808.
• Stewart AE, Dowd S, Keyse SM, McDonald NQ (Feb 1999). "Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation". Nature Structural Biology 6 (2): 174–81. doi:10.1038/5861. PMID 10048930.
• Rössig L, Hermann C, Haendeler J, Assmus B, Zeiher AM, Dimmeler S (Jan 2002). "Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis". Basic Research in Cardiology 97 (1): 1–8. doi:10.1007/s395-002-8381-2. PMID 11998972.
• Furukawa T, Sunamura M, Motoi F, Matsuno S, Horii A (Jun 2003). "Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer". The American Journal of Pathology 162 (6): 1807–15. doi:10.1016/S0002-9440(10)64315-5. PMC 1868131. PMID 12759238.
• Kim HS, Song MC, Kwak IH, Park TJ, Lim IK (Sep 2003). "Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence". The Journal of Biological Chemistry 278 (39): 37497–510. doi:10.1074/jbc.M211739200. PMID 12840032.
• Kim Y, Rice AE, Denu JM (Dec 2003). "Intramolecular dephosphorylation of ERK by MKP3". Biochemistry 42 (51): 15197–207. doi:10.1021/bi035346b. PMID 14690430.
• Karlsson M, Mathers J, Dickinson RJ, Mandl M, Keyse SM (Oct 2004). "Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal". The Journal of Biological Chemistry 279 (40): 41882–91. doi:10.1074/jbc.M406720200. PMID 15269220.
• Marchetti S, Gimond C, Chambard JC, Touboul T, Roux D, Pouysségur J, Pagès G (Jan 2005). "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation". Molecular and Cellular Biology 25 (2): 854–64. doi:10.1128/MCB.25.2.854-864.2005. PMC 543408. PMID 15632084.
• Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (Mar 2005). "Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases". Cell 120 (5): 649–61. doi:10.1016/j.cell.2004.12.041. PMID 15766528.
• Xu S, Furukawa T, Kanai N, Sunamura M, Horii A (2005). "Abrogation of DUSP6 by hypermethylation in human pancreatic cancer". Journal of Human Genetics 50 (4): 159–67. doi:10.1007/s10038-005-0235-y. PMID 15824892.
• Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, Takeda K, Matsuno S, Horii A (Aug 2005). "Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas". Modern Pathology 18 (8): 1034–42. doi:10.1038/modpathol.3800383. PMID 15832194.