Difference between revisions of "Phosphatase Family PHP"
From PhosphataseWiki
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PHP|PHP Superfamily]]: [[Phosphatase_Family_PHP|PHP Family]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PHP|PHP Superfamily]]: [[Phosphatase_Family_PHP|PHP Family]] | ||
| − | + | PHP is the only phosphatase known to be histidine-specific. | |
| − | == | + | === Evolution === |
| − | + | PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in fruit fly. | |
| + | === Domain === | ||
| + | PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed <cite>Gong</cite>. | ||
| − | == | + | === Functions === |
| − | + | Several substrates have been reported, including ''beta'' subunit of heterotrimeric G proteins <cite>Maurer04</cite>, the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) <cite>Klumpp03</cite>, and the Ca2+-activated K+ channel KCa3.1 <cite>Skolnik08</cite>. These are known or suspected substrates of the nucleoside diphosphate kinases ([http://kinase.com/wiki/index.php/Kinase_Group_NDK NDK]). | |
| + | Its role in neuronal cells is particularly interesting. In ''C. elegans'', the ortholog is expressed exclusively in neurons <cite>Klumpp02</cite>. In human cells, the overexpression of PHPT1 decreases the activity of adenosine 5’-triphosphate-citrate lyase (ACL) and reduces the viability of neuronal cells <cite>Klumpp09</cite>. | ||
| − | == References == | + | |
| + | === References === | ||
<biblio> | <biblio> | ||
#Gong pmid=18991813 | #Gong pmid=18991813 | ||
Revision as of 17:43, 1 January 2015
Phosphatase Classification: PHP Superfamily: PHP Family
PHP is the only phosphatase known to be histidine-specific.
Evolution
PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in fruit fly.
Domain
PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed [1].
Functions
Several substrates have been reported, including 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).
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 adenosine 5’-triphosphate-citrate lyase (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 |
