Difference between revisions of "Phosphatase Family PHP"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PHP|PHP Superfamily]]: [[Phosphatase_Famiyl_PHP|PHP Family]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PHP|PHP Superfamily]]: [[Phosphatase_Famiyl_PHP|PHP Family]] | ||
| − | + | It is the only phosphatase known to be histidine-specific. It is found throughout eukaryotes, though lost from fungi. In most species, it is a single-copy gene (PHPT1 in human), but four were found in fruit fly. It's catalytic domain has been solved and a potential enzymatic mechanism proposed <cite>Gong</cite>. Its fold is not related to that of any other enzyme. | |
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== Substrates and related kinase == | == Substrates and related kinase == | ||
Revision as of 16:38, 2 May 2014
Phosphatase Classification: PHP Superfamily: PHP Family
It is the only phosphatase known to be histidine-specific. It is found throughout eukaryotes, though lost from fungi. In most species, it is a single-copy gene (PHPT1 in human), but four were found in fruit fly. It's catalytic domain has been solved and a potential enzymatic mechanism proposed [1]. Its fold is not related to that of any other enzyme.
The known substrates are beta subunit of heterotrimeric G proteins [2], the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) [3], and the Ca2+-activated K+ channel KCa3.1 [4]. These are known or suspected substrates of the nucleoside diphosphate kinases (NDK).
Involved in nervous system
Its role in neuronal cells is particularly interesting. In C. elegans, the ortholog is expressed exclusively in neurons [5]. In human cells, the overexpression of PHPT1 decreases the activity of ACL and reduces the viability of neuronal cells [6].
References
- Gong W, Li Y, Cui G, Hu J, Fang H, Jin C, and Xia B. Solution structure and catalytic mechanism of human protein histidine phosphatase 1. Biochem J. 2009 Mar 1;418(2):337-44. DOI:10.1042/BJ20081571 |
- Mäurer A, Wieland T, Meissl F, Niroomand F, Mehringer R, Krieglstein J, and Klumpp S. The beta-subunit of G proteins is a substrate of protein histidine phosphatase. Biochem Biophys Res Commun. 2005 Sep 9;334(4):1115-20. DOI:10.1016/j.bbrc.2005.06.200 |
- Klumpp S, Bechmann G, Mäurer A, Selke D, and Krieglstein J. ATP-citrate lyase as a substrate of protein histidine phosphatase in vertebrates. Biochem Biophys Res Commun. 2003 Jun 20;306(1):110-5. DOI:10.1016/s0006-291x(03)00920-3 |
- Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, and Skolnik EY. Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14442-6. DOI:10.1073/pnas.0803678105 |
- Klumpp S, Hermesmeier J, Selke D, Baumeister R, Kellner R, and Krieglstein J. Protein histidine phosphatase: a novel enzyme with potency for neuronal signaling. J Cereb Blood Flow Metab. 2002 Dec;22(12):1420-4. DOI:10.1097/01.wcb.0000045041.03034.99 |
- Klumpp S, Faber D, Fischer D, Litterscheid S, and Krieglstein J. Role of protein histidine phosphatase for viability of neuronal cells. Brain Res. 2009 Apr 6;1264:7-12. DOI:10.1016/j.brainres.2008.12.052 |
