Difference between revisions of "Phosphatase Family PHP"
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* Motif 4: 75 GGGx[RK]IxH 81 | * Motif 4: 75 GGGx[RK]IxH 81 | ||
* Motif 5: 92 GxSxxxGxAxH 102 | * Motif 5: 92 GxSxxxGxAxH 102 | ||
| − | His-53 and Lys-21 are critical to its catalytic activity (see below). | + | Note: His-53 and Lys-21 are critical to its catalytic activity (see below). |
=== Domain === | === Domain === | ||
Revision as of 01:44, 2 June 2015
Phosphatase Classification: PHP Fold: 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. The most conserved positions include:
- Motif 1: 18 GxFKY 22
- Motif 2: 45 RG 46
- Motif 3: H 53
- Motif 4: 75 GGGx[RK]IxH 81
- Motif 5: 92 GxSxxxGxAxH 102
Note: His-53 and Lys-21 are critical to its catalytic activity (see below).
Domain
PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed (see figure 4 in [1]): (i) the substrate binds to the protein by forming four H-bonds; (ii) His-53 acts as a general base to activate a water molecule, which in turn functions as a nucleophile to attack the phosphate substrate; and (iii) the positively charged amine group of Lys-21 helps in stabilizing the transition state during catalysis.
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. Human PHP (PHPT1) is widely expressed across different tissues, most abundantly in cerebellum and pituitary, according to RNA-seq data from GTEx. In C. elegans, PHP 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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