Phosphatase Family PHP

Phosphatase Classification: PHP Superfamily: PHP Family

This superfamily has a single family, subfamily and gene PHPT1 in human. Though it is usually described "found in vertebrates and absence in fungi and bacteria", we can find it in non-vertebrates, even in single-cellular eukaryote Monosiga, Dictyostelium and some basal individual eukaryotes like T. gondii and Volvox. In most species, it is a single-copy gene, but four were found in fruit fly including three divergent from the one conserved across the species.

Substrates and related kinase

The known substrates are beta subunit of heterotrimeric G proteins [1], the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) [2], and the Ca2+-activated K+ channel KCa3.1 [3]. It usually works with nucleoside diphosphate kinase (NDPK).

Involved in nervous system

Its role in neuronal cells is particularly interesting. In C. elegans, the ortholog is expressed exclusively in neurons [4]. In human cells, the overexpression of PHPT1 decreases the activity of ACL and reduces the viability of neuronal cells [5].

References

1. 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 |
2. 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 |
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 |
4. 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 |
5. 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 |