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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Dual specificity phosphatase 6''' ('''DUSP6''') is an [[enzyme]] that in humans is encoded by the ''DUSP6''  [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DUSP6 dual specificity phosphatase 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1848| accessdate = }}</ref><ref name="pmid8626780">{{cite journal | vauthors = Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S | title = MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 8 | pages = 4319–26 | date = Feb 1996 | pmid = 8626780 | doi = 10.1074/jbc.271.8.4319 | url = http://www.jbc.org/cgi/content/full/271/8/4319 }}</ref><ref name="pmid9205128">{{cite journal | vauthors = Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A | title = Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7) | journal = Genomics | volume = 42 | issue = 3 | pages = 524–7 | date = Jun 1997 | pmid = 9205128 | doi = 10.1006/geno.1997.4756 }}</ref>
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| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_DUSP6_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1hzm.
| PDB = {{PDB2|1hzm}}, {{PDB2|1mkp}}
| Name = Dual specificity phosphatase 6
| HGNCid = 3072
| Symbol = DUSP6
| AltSymbols =; MKP3; PYST1
| OMIM = 602748
| ECnumber = 
| Homologene = 55621
| MGIid = 1914853
| GeneAtlas_image1 = PBB_GE_DUSP6_208892_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_DUSP6_208891_at_tn.png
| GeneAtlas_image3 = PBB_GE_DUSP6_208893_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004722 |text = protein serine/threonine phosphatase activity}} {{GNF_GO|id=GO:0004725 |text = protein tyrosine phosphatase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0017017 |text = MAP kinase tyrosine/serine/threonine phosphatase activity}}
| Component = {{GNF_GO|id=GO:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0000188 |text = inactivation of MAPK activity}} {{GNF_GO|id=GO:0006470 |text = protein amino acid dephosphorylation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1848
    | Hs_Ensembl = ENSG00000139318
    | Hs_RefseqProtein = NP_001937
    | Hs_RefseqmRNA = NM_001946
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 88265970
    | Hs_GenLoc_end = 88270427
    | Hs_Uniprot = Q16828
    | Mm_EntrezGene = 67603
    | Mm_Ensembl = ENSMUSG00000019960
    | Mm_RefseqmRNA = NM_026268
    | Mm_RefseqProtein = NP_080544
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 98692919
    | Mm_GenLoc_end = 98697172
    | Mm_Uniprot = Q3U786
  }}
}}
'''Dual specificity phosphatase 6''', also known as '''DUSP6''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DUSP6 dual specificity phosphatase 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1848| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The [[protein]] encoded by this gene is a member of the dual specificity protein [[phosphatase]] subfamily. These phosphatases inactivate their target [[kinase]]s by dephosphorylating both the [[phosphoserine]]/[[threonine]] and [[phosphotyrosine]] residues. They negatively regulate members of the [[mitogen-activated protein kinase|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 [[MAPK1|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.<ref name="entrez" /> Upregulation of MKP-3 has been shown to alleviate chronic postoperative pain.<ref>{{cite journal | vauthors = Saha M, Skopelja S, Martinez E, Alvarez DL, Liponis BS, Romero-Sandoval EA | title = 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 | journal = The Journal of Neuroscience | volume = 33 | issue = 43 | pages = 17182–7 | date = Oct 2013 | pmid = 24155322 | doi = 10.1523/JNEUROSCI.5605-12.2013 | url = http://www.jneurosci.org/content/33/43/17182 }}</ref><ref>{{Cite journal|last=Skopelja-Gardner|first=Sladjana|last2=Saha|first2=Madhurima|last3=Alvarado-Vazquez|first3=Perla Abigail|last4=Liponis|first4=Brenna S|last5=Martinez|first5=Elena|last6=Romero-Sandoval|first6=E. Alfonso|date=2017-03-28|title=Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical wound is necessary for the resolution of postoperative pain in mice|url=https://doi.org/10.2147/JPR.S129826|journal=Journal of Pain Research|language=English|volume=Volume 10|pages=763–774|doi=10.2147/jpr.s129826}}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: DUSP6 dual specificity phosphatase 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1848| accessdate = }}</ref>
}}


==References==
== Interactions ==
{{reflist|2}}
 
==Further reading==
DUSP6 has been shown to [[Protein-protein interaction|interact]] with [[MAPK3]].<ref name=pmid9535927>{{cite journal | vauthors = Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S | title = The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 15 | pages = 9323–9 | date = Apr 1998 | pmid = 9535927 | doi = 10.1074/jbc.273.15.9323 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
| citations =
* {{cite journal | vauthors = Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S | title = MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 8 | pages = 4319–26 | date = Feb 1996 | pmid = 8626780 | doi = 10.1074/jbc.271.8.4319 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM | title = Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase | journal = The EMBO Journal | volume = 15 | issue = 14 | pages = 3621–32 | date = Jul 1996 | pmid = 8670865 | pmc = 451978 | doi =  }}
*{{cite journal | author=Muda M, Boschert U, Dickinson R, ''et al.'' |title=MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase. |journal=J. Biol. Chem. |volume=271 |issue= 8 |pages= 4319-26 |year= 1996 |pmid= 8626780 |doi= }}
* {{cite journal | vauthors = Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A | title = Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7) | journal = Genomics | volume = 42 | issue = 3 | pages = 524–7 | date = Jun 1997 | pmid = 9205128 | doi = 10.1006/geno.1997.4756 }}
*{{cite journal | author=Groom LA, Sneddon AA, Alessi DR, ''et al.'' |title=Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. |journal=EMBO J. |volume=15 |issue= 14 |pages= 3621-32 |year= 1996 |pmid= 8670865 |doi=  }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Smith A, Price C, Cullen M, ''et al.'' |title=Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). |journal=Genomics |volume=42 |issue= 3 |pages= 524-7 |year= 1997 |pmid= 9205128 |doi= 10.1006/geno.1997.4756 }}
* {{cite journal | vauthors = Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S | title = The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 15 | pages = 9323–9 | date = Apr 1998 | pmid = 9535927 | doi = 10.1074/jbc.273.15.9323 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Furukawa T, Yatsuoka T, Youssef EM, Abe T, Yokoyama T, Fukushige S, Soeda E, Hoshi M, Hayashi Y, Sunamura M, Kobari M, Horii A | title = Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer | journal = Cytogenetics and Cell Genetics | volume = 82 | issue = 3-4 | pages = 156–9 | year = 1999 | pmid = 9858808 | doi = 10.1159/000015091 }}
*{{cite journal | author=Muda M, Theodosiou A, Gillieron C, ''et al.'' |title=The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity. |journal=J. Biol. Chem. |volume=273 |issue= 15 |pages= 9323-9 |year= 1998 |pmid= 9535927 |doi= }}
* {{cite journal | vauthors = Stewart AE, Dowd S, Keyse SM, McDonald NQ | title = Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation | journal = Nature Structural Biology | volume = 6 | issue = 2 | pages = 174–81 | date = Feb 1999 | pmid = 10048930 | doi = 10.1038/5861 }}
*{{cite journal | author=Furukawa T, Yatsuoka T, Youssef EM, ''et al.'' |title=Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer. |journal=Cytogenet. Cell Genet. |volume=82 |issue= 3-4 |pages= 156-9 |year= 1999 |pmid= 9858808 |doi= }}
* {{cite journal | vauthors = Rössig L, Hermann C, Haendeler J, Assmus B, Zeiher AM, Dimmeler S | title = Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis | journal = Basic Research in Cardiology | volume = 97 | issue = 1 | pages = 1–8 | date = Jan 2002 | pmid = 11998972 | doi = 10.1007/s395-002-8381-2 }}
*{{cite journal | author=Stewart AE, Dowd S, Keyse SM, McDonald NQ |title=Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation. |journal=Nat. Struct. Biol. |volume=6 |issue= 2 |pages= 174-81 |year= 1999 |pmid= 10048930 |doi= 10.1038/5861 }}
* {{cite journal | vauthors = Furukawa T, Sunamura M, Motoi F, Matsuno S, Horii A | title = Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer | journal = The American Journal of Pathology | volume = 162 | issue = 6 | pages = 1807–15 | date = Jun 2003 | pmid = 12759238 | pmc = 1868131 | doi = 10.1016/S0002-9440(10)64315-5 }}
*{{cite journal | author=Rössig L, Hermann C, Haendeler J, ''et al.'' |title=Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis. |journal=Basic Res. Cardiol. |volume=97 |issue= 1 |pages= 1-8 |year= 2002 |pmid= 11998972 |doi= }}
* {{cite journal | vauthors = Kim HS, Song MC, Kwak IH, Park TJ, Lim IK | title = 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 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 39 | pages = 37497–510 | date = Sep 2003 | pmid = 12840032 | doi = 10.1074/jbc.M211739200 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Kim Y, Rice AE, Denu JM | title = Intramolecular dephosphorylation of ERK by MKP3 | journal = Biochemistry | volume = 42 | issue = 51 | pages = 15197–207 | date = Dec 2003 | pmid = 14690430 | doi = 10.1021/bi035346b }}
*{{cite journal | author=Furukawa T, Sunamura M, Motoi F, ''et al.'' |title=Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer. |journal=Am. J. Pathol. |volume=162 |issue= 6 |pages= 1807-15 |year= 2003 |pmid= 12759238 |doi= }}
* {{cite journal | vauthors = Karlsson M, Mathers J, Dickinson RJ, Mandl M, Keyse SM | title = 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 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 40 | pages = 41882–91 | date = Oct 2004 | pmid = 15269220 | doi = 10.1074/jbc.M406720200 }}
*{{cite journal | author=Kim HS, Song MC, Kwak IH, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 37497-510 |year= 2003 |pmid= 12840032 |doi= 10.1074/jbc.M211739200 }}
* {{cite journal | vauthors = Marchetti S, Gimond C, Chambard JC, Touboul T, Roux D, Pouysségur J, Pagès G | title = Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation | journal = Molecular and Cellular Biology | volume = 25 | issue = 2 | pages = 854–64 | date = Jan 2005 | pmid = 15632084 | pmc = 543408 | doi = 10.1128/MCB.25.2.854-864.2005 }}
*{{cite journal | author=Kim Y, Rice AE, Denu JM |title=Intramolecular dephosphorylation of ERK by MKP3. |journal=Biochemistry |volume=42 |issue= 51 |pages= 15197-207 |year= 2004 |pmid= 14690430 |doi= 10.1021/bi035346b }}
* {{cite journal | vauthors = Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M | title = Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases | journal = Cell | volume = 120 | issue = 5 | pages = 649–61 | date = Mar 2005 | pmid = 15766528 | doi = 10.1016/j.cell.2004.12.041 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{cite journal | vauthors = Xu S, Furukawa T, Kanai N, Sunamura M, Horii A | title = Abrogation of DUSP6 by hypermethylation in human pancreatic cancer | journal = Journal of Human Genetics | volume = 50 | issue = 4 | pages = 159–67 | year = 2005 | pmid = 15824892 | doi = 10.1007/s10038-005-0235-y }}
*{{cite journal | author=Karlsson M, Mathers J, Dickinson RJ, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=279 |issue= 40 |pages= 41882-91 |year= 2004 |pmid= 15269220 |doi= 10.1074/jbc.M406720200 }}
* {{cite journal | vauthors = Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, Takeda K, Matsuno S, Horii A | title = Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas | journal = Modern Pathology | volume = 18 | issue = 8 | pages = 1034–42 | date = Aug 2005 | pmid = 15832194 | doi = 10.1038/modpathol.3800383 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal | author=Marchetti S, Gimond C, Chambard JC, ''et al.'' |title=Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation. |journal=Mol. Cell. Biol. |volume=25 |issue= 2 |pages= 854-64 |year= 2005 |pmid= 15632084 |doi= 10.1128/MCB.25.2.854-864.2005 }}
*{{cite journal  | author=Kamata H, Honda S, Maeda S, ''et al.'' |title=Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. |journal=Cell |volume=120 |issue= 5 |pages= 649-61 |year= 2005 |pmid= 15766528 |doi= 10.1016/j.cell.2004.12.041 }}
*{{cite journal  | author=Xu S, Furukawa T, Kanai N, ''et al.'' |title=Abrogation of DUSP6 by hypermethylation in human pancreatic cancer. |journal=J. Hum. Genet. |volume=50 |issue= 4 |pages= 159-67 |year= 2005 |pmid= 15824892 |doi= 10.1007/s10038-005-0235-y }}
*{{cite journal  | author=Furukawa T, Fujisaki R, Yoshida Y, ''et al.'' |title=Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas. |journal=Mod. Pathol. |volume=18 |issue= 8 |pages= 1034-42 |year= 2005 |pmid= 15832194 |doi= 10.1038/modpathol.3800383 }}
}}
{{refend}}
{{refend}}


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Revision as of 01:59, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Dual specificity phosphatase 6 (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 MKP-3 has been shown to alleviate chronic postoperative pain.[4][5]

Interactions

DUSP6 has been shown to interact with MAPK3.[6]

References

  1. ↑ 1.0 1.1 "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. ↑ Skopelja-Gardner, Sladjana; Saha, Madhurima; Alvarado-Vazquez, Perla Abigail; Liponis, Brenna S; Martinez, Elena; Romero-Sandoval, E. Alfonso (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. Volume 10: 763–774. doi:10.2147/jpr.s129826.
  6. ↑ 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


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