Difference between revisions of "Phosphatase Subfamily PHP"

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Phosphatase Classification: PHP Fold: PHP Superfamily: PHP Family

PHP is the only phosphatase known to be histidine-specific.


PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in fruit fly.


PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed [1].


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].


  1. 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 | PubMed ID:18991813 | HubMed [Gong]
  2. 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 | PubMed ID:16039992 | HubMed [Maurer04]
  3. 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 | PubMed ID:12788074 | HubMed [Klumpp03]
  4. 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 | PubMed ID:18796614 | HubMed [Skolnik08]
  5. 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 | PubMed ID:12468887 | HubMed [Klumpp02]
  6. 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 | PubMed ID:19138678 | HubMed [Klumpp09]
All Medline abstracts: PubMed | HubMed