DUSP6

Dual specificity phosphatase 6
PDB rendering based on 1hzm.
Available structures PDB 1HZM, 1MKP
Identifiers
Symbols	DUSP6; MKP3; PYST1
External IDs	OMIM: 602748 MGI: 1914853 HomoloGene: 55621 GeneCards: DUSP6 Gene
Gene Ontology Molecular function • protein tyrosine phosphatase activity • hydrolase 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-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • Toll signaling pathway • dorsal/ventral pattern formation • response to organic cyclic compound • cell differentiation • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • peptidyl-tyrosine dephosphorylation • peptidyl-tyrosine dephosphorylation • regulation of fibroblast growth factor receptor signaling pathway • response to drug • regulation of endodermal cell fate specification • positive regulation of apoptosis • innate immune response • nerve growth factor receptor signaling pathway • stress-activated MAPK cascade • response to nitrosative stress • regulation of heart growth • negative regulation of ERK1 and ERK2 cascade • response to growth factor stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1848	67603
Ensembl	ENSG00000139318	ENSMUSG00000019960
UniProt	Q16828	Q3U786
RefSeq (mRNA)	NM_001946.2	NM_026268.3
RefSeq (protein)	NP_001937.2	NP_080544.1
Location (UCSC)	Chr 12: 89.74 – 89.75 Mb	Chr 10: 98.73 – 98.73 Mb
PubMed search	[1]	[2]

Dual specificity phosphatase 6, also known as DUSP6, is an enzyme which 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]

Interactions

DUSP6 has been shown to interact with MAPK3.^[4]

References

1. ^ ^{a b} "Entrez Gene: DUSP6 dual specificity phosphatase 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1848. 
2. ^ 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". J. Biol. Chem. 271 (8): 4319–26. doi:10.1074/jbc.271.8.4319. PMID 8626780. http://www.jbc.org/cgi/content/full/271/8/4319. 
3. ^ 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. 
4. ^ 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". J. Biol. Chem. (UNITED STATES) 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. ISSN 0021-9258. PMID 9535927. 

Further reading

• Maruyama K, Sugano S (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, et al. (1996). "MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". J. Biol. Chem. 271 (8): 4319–26. doi:10.1074/jbc.271.8.4319. PMID 8626780. 
• Groom LA, Sneddon AA, Alessi DR, et al. (1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase". EMBO J. 15 (14): 3621–32. PMC 451978. PMID 8670865. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=451978. 
• Smith A, Price C, Cullen M, et al. (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, et al. (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, et al. (1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". J. Biol. Chem. 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID 9535927. 
• Furukawa T, Yatsuoka T, Youssef EM, et al. (1999). "Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenet. Cell Genet. 82 (3–4): 156–9. doi:10.1159/000015091. PMID 9858808. 
• Stewart AE, Dowd S, Keyse SM, McDonald NQ (1999). "Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation". Nat. Struct. Biol. 6 (2): 174–81. doi:10.1038/5861. PMID 10048930. 
• Rössig L, Hermann C, Haendeler J, et al. (2002). "Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis". Basic Res. Cardiol. 97 (1): 1–8. doi:10.1007/s395-002-8381-2. PMID 11998972. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Furukawa T, Sunamura M, Motoi F, et al. (2003). "Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer". Am. J. Pathol. 162 (6): 1807–15. doi:10.1016/S0002-9440(10)64315-5. PMC 1868131. PMID 12759238. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1868131. 
• Kim HS, Song MC, Kwak IH, et al. (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". J. Biol. Chem. 278 (39): 37497–510. doi:10.1074/jbc.M211739200. PMID 12840032. 
• Kim Y, Rice AE, Denu JM (2004). "Intramolecular dephosphorylation of ERK by MKP3". Biochemistry 42 (51): 15197–207. doi:10.1021/bi035346b. PMID 14690430. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Karlsson M, Mathers J, Dickinson RJ, et al. (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". J. Biol. Chem. 279 (40): 41882–91. doi:10.1074/jbc.M406720200. PMID 15269220. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Marchetti S, Gimond C, Chambard JC, et al. (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". Mol. Cell. Biol. 25 (2): 854–64. doi:10.1128/MCB.25.2.854-864.2005. PMC 543408. PMID 15632084. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=543408. 
• Kamata H, Honda S, Maeda S, et al. (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, et al. (2005). "Abrogation of DUSP6 by hypermethylation in human pancreatic cancer". J. Hum. Genet. 50 (4): 159–67. doi:10.1007/s10038-005-0235-y. PMID 15824892. 
• Furukawa T, Fujisaki R, Yoshida Y, et al. (2005). "Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas". Mod. Pathol. 18 (8): 1034–42. doi:10.1038/modpathol.3800383. PMID 15832194.