Diphosphoinositol polyphosphate phosphohydrolase 1

Definition:

Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphosphate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway (By similarity). Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility.

References:

[1]. David I Fisher, et al. Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate. J Biol Chem. 2002 Dec 6;277(49):47313-7. [Content Brief]

[2]. S T Safrany, et al. The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein. J Biol Chem. 1999 Jul 30;274(31):21735-40. [Content Brief]

[3]. Ewa Grudzien-Nogalska, et al. Nudt3 is an mRNA decapping enzyme that modulates cell migration. RNA. 2016 May;22(5):773-81. [Content Brief]

[4]. S T Safrany, et al. A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase. EMBO J. 1998 Nov 16;17(22):6599-607. [Content Brief]

[5]. X Yang, et al. Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates. J Biol Chem. 1999 Dec 10;274(50):35434-40. [Content Brief]

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