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| {{STRUCTURE_1ohe| PDB=1ohe | SIZE=400 | SCENE= |right|CAPTION=Human Cdc14B2 core domain (grey) complex with tripeptide (green) and acetyl (PDB code [[1ohe]]). }}
| | <StructureSection load='1ohe' size='350' side='right' scene='' caption='Human Cdc14B2 core domain (grey) complex with tripeptide (green) and acetyl (PDB code [[1ohe]]).'> |
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| == Function == | | == Function == |
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| Myotubularin mutations are responsible for the hereditary motor disease Charcot-Marie-Tooth disease.<ref>PMID:12045210</ref> | | Myotubularin mutations are responsible for the hereditary motor disease Charcot-Marie-Tooth disease.<ref>PMID:12045210</ref> |
| | | </StructureSection> |
| ==3D structures of dual specificity phosphatase== | | ==3D structures of dual specificity phosphatase== |
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Revision as of 14:01, 7 February 2016
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Function
Dual specificity phosphatase (DUSP) is a phosphatase which acts on tyrosine, serine or threonine residues. There are several DUSP enzymes in mammals sharing a common catalytic mechanism. The DUSP include:
• Slingshot phosphatase[1]
• Phosphatase of regenerating liver (PRL)[2]
• Cdc14 leads to mitotic exit by dephosphorylation of targets of the protein kinase Cdk1.[3]
• Cdc25 activates Cdk1 by its dephosphorylation.[4]
• PTEN (Phosphatase and TEnsin homolog) dephosphorylates phosphasitide substrates.[5]
• Myotubularin dephosphorylates phosphadinylinositol 3-phosphate and phosphadinylinositol (3,5)-bi-phosphate[6]
• MAPK phosphatase see MAP kinase phosphatase
Relevance
Cdc25A and Cdc25B are overexpressed in several types of cancers and their inhibitors are being tested as chemotherapeutic agents.
PTEN gene is mutated with high frequency in a variety of human cancers.[7]
Phosphatase of regenerating liver is overexpressed in several types of cancers.
Disease
Myotubularin mutations are responsible for the hereditary motor disease Charcot-Marie-Tooth disease.[8]
- ↑ Kligys K, Claiborne JN, DeBiase PJ, Hopkinson SB, Wu Y, Mizuno K, Jones JC. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes. J Biol Chem. 2007 Nov 2;282(44):32520-8. Epub 2007 Sep 11. PMID:17848544 doi:https://dx.doi.org/10.1074/jbc.M707041200
- ↑ Walls CD, Iliuk A, Bai Y, Wang M, Tao WA, Zhang ZY. Phosphatase of regenerating liver 3 (PRL3) provokes a tyrosine phosphoproteome to drive prometastatic signal transduction. Mol Cell Proteomics. 2013 Dec;12(12):3759-77. doi: 10.1074/mcp.M113.028886. Epub , 2013 Sep 12. PMID:24030100 doi:https://dx.doi.org/10.1074/mcp.M113.028886
- ↑ Stegmeier F, Amon A. Closing mitosis: the functions of the Cdc14 phosphatase and its regulation. Annu Rev Genet. 2004;38:203-32. PMID:15568976 doi:https://dx.doi.org/10.1146/annurev.genet.38.072902.093051
- ↑ Kristjansdottir K, Rudolph J. Cdc25 phosphatases and cancer. Chem Biol. 2004 Aug;11(8):1043-51. PMID:15324805 doi:https://dx.doi.org/10.1016/j.chembiol.2004.07.007
- ↑ Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell. 1999 Oct 29;99(3):323-34. PMID:10555148
- ↑ Nandurkar HH, Layton M, Laporte J, Selan C, Corcoran L, Caldwell KK, Mochizuki Y, Majerus PW, Mitchell CA. Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8660-5. Epub 2003 Jul 7. PMID:12847286 doi:https://dx.doi.org/10.1073/pnas.1033097100
- ↑ Pulido R, Hooft van Huijsduijnen R. Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease. FEBS J. 2008 Mar;275(5):848-66. doi: 10.1111/j.1742-4658.2008.06250.x. PMID:18298792 doi:https://dx.doi.org/10.1111/j.1742-4658.2008.06250.x
- ↑ Berger P, Bonneick S, Willi S, Wymann M, Suter U. Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1. Hum Mol Genet. 2002 Jun 15;11(13):1569-79. PMID:12045210
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3D structures of dual specificity phosphatase
Updated on 07-February-2016
{"openlevels":0}
- Slingshot phosphatase (SSH)
- Phosphatase of regenerating liver (PRL)
- Cdc14
- 1ohc, 1ohd – hCdc14B2 core domain
- 1ohe – hCdc14B2 core domain + peptide
- Cdc25
- 1qb0, 1cwr, 1cws, 1cwt, 1ym9, 1ymd, 1ymk, 1yml, 1ys0, 2uzq – hCdc25B catalytic domain
- 2a2k, 2ifd, 2ifv – hCdc25B catalytic domain (mutant)
- Phosphoinositide phosphatase PTEN
- Myotubularin-related protein (MTMR)
- 1zvr – hMTMR2 PH-gram and phosphatase domains (mutant)
- 1zsq - hMTMR2 PH-gram and phosphatase domains (mutant) + phosphatidylinositol 3-phosphate
- 1m7r, 1lw3 - hMTMR2 PH-gram and phosphatase domains (mutant) + phosphate
- 2yf0 – hMTMR6
- MAPK phosphatase see MAP kinase phosphatase
References
