Phosphatase Fold PHP
Phosphatase Classification: PHP Fold
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
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