Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase: a novel metallophosphoesterase family preferentially expressed in rodent immune cells
Résumé
The Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase (ADPRibase-Mn) is isolated from rat liver supernatants after separation from Mg2+-activated ADP-ribose pyrophosphatases devoid of CDP-alcohol pyrophosphatase activity (ADPRibase-I and ADPRibase-II). The latter are putative Nudix hydrolases, while the molecular identity of ADPRibase-Mn is unknown. MALDI mass spectrometry data from rat ADPRibase-Mn pointed to a hypothetical protein that was cloned and expressed, and showed the expected specificity. It is encoded by the RGD1309906 rat gene, so far annotated just as 'hydrolase'. ADPRibase-Mn is not a Nudix hydrolase, but it shows the sequence and structural features typical of the metallophosphoesterase superfamily. It may constitute a protein family of their own, which appears to be specific to vertebrates, plants and algae. ADP-ribose was successfully docked to a model of rat ADPRibase-Mn revealing its putative active centre. Microarray data from the GEO database indicated the mouse gen 2310004I24Rik, orthologous of RGD1309906, is preferentially expressed in immune cells. This was confirmed by northern and activity assay of ADPRibase-Mn in rat tissues. A possible role of ADPRibase-Mn in immune cell signaling is suggested by the second messenger role of ADP-ribose, that activates TRPM2 ion channels as a mediator of oxidative/nitrosative stress, and by the signaling function assigned to many of the microarray profile neighbours of 2310004I24Rik. Furthermore, an influence of ADPRibase-Mn in the CDP-choline or CDP-ethanolamine pathways of phospholipid biosynthesis cannot be discarded.
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