Phosphatase Family PHP
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
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