DUSP6

Dual specificity phosphatase 6 (DUSP6) is an enzyme that in humans is encoded by the DUSP6 gene.[5][6][7]

DUSP6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1HZM, 1MKP
Identifiers
Aliases	DUSP6, HH19, MKP3, PYST1, dual specificity phosphatase 6
External IDs	OMIM: 602748 MGI: 1914853 HomoloGene: 55621 GeneCards: DUSP6
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q21.33 Start 89,347,235 bp[1] End 89,352,501 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 D1 Start 99,263,231 bp[2] End 99,267,489 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphoprotein phosphatase activity • phosphatase activity • hydrolase activity • MAP kinase tyrosine/serine/threonine phosphatase activity • protein tyrosine phosphatase activity • protein tyrosine/serine/threonine phosphatase activity Cellular component • nucleoplasm • cytosol • cytoplasm Biological process • negative regulation of protein phosphorylation • cell differentiation • positive regulation of cell death • response to organic cyclic compound • regulation of fibroblast growth factor receptor signaling pathway • inactivation of MAPK activity • protein dephosphorylation • response to organic substance • MAPK cascade • activation of MAPK activity • response to nitrosative stress • positive regulation of apoptotic process • negative regulation of ERK1 and ERK2 cascade • peptidyl-tyrosine dephosphorylation • response to growth factor • dorsal/ventral pattern formation • regulation of endodermal cell fate specification • response to drug • dephosphorylation • regulation of heart growth Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1848	67603
Ensembl	ENSG00000139318	ENSMUSG00000019960
UniProt	Q16828	Q9DBB1
RefSeq (mRNA)	NM_022652 NM_001946	NM_026268
RefSeq (protein)	NP_001937 NP_073143	NP_080544
Location (UCSC)	Chr 12: 89.35 – 89.35 Mb	Chr 10: 99.26 – 99.27 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5] Upregulation of MKP-3 has been shown to alleviate chronic postoperative pain.[8][9]

Interactions

DUSP6 has been shown to interact with MAPK3.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000139318 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019960 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: DUSP6 dual specificity phosphatase 6".
6. Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S (February 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.
7. Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A (June 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.
8. Saha M, Skopelja S, Martinez E, Alvarez DL, Liponis BS, Romero-Sandoval EA (October 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. PMC 6618446. PMID 24155322.
9. Skopelja-Gardner S, Saha M, Alvarado-Vazquez PA, Liponis BS, Martinez E, Romero-Sandoval EA (2017-03-28). "Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical wound is necessary for the resolution of postoperative pain in mice". Journal of Pain Research. 10: 763–774. doi:10.2147/jpr.s129826. PMC 5378457. PMID 28405172.
10. Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (April 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 (January 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.
• Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM (July 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. doi:10.1002/j.1460-2075.1996.tb00731.x. PMC 451978. PMID 8670865.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 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.
• 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 (February 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 (January 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 (June 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 (September 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 (December 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 (October 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 (January 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 (March 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 (August 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.

External links

• Overview of all the structural information available in the PDB for UniProt: Q16828 (Dual specificity protein phosphatase 6) at the PDBe-KB.