title: Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase: a novel metallophosphoesterase family preferentially expressed in rodent immune cells.
abstract: ADPRibase-Mn (Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase) was earlier isolated from rat liver supernatants after separation from ADPRibase-I and ADPRibase-II (Mg2+-activated ADP-ribose pyrophosphatases devoid of CDP-alcohol pyrophosphatase activity). The last mentioned are putative Nudix hydrolases, whereas the molecular identity of ADPRibase-Mn is unknown. MALDI (matrix-assisted laser-desorption ionization) MS 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, which so far has been annotated simply 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 its own, the members of which appear 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 (Gene Expression Omnibus) database indicated that the mouse gene 2310004I24Rik, an orthologue of RGD1309906, is preferentially expressed in immune cells. This was confirmed by Northern-blot and activity assay of ADPRibase-Mn in rat tissues. A possible role of ADPRibase-Mn in immune cell signalling is suggested by the second-messenger role of ADP-ribose, which activates TRPM2 (transient receptor potential melastatin channel-2) ion channels as a mediator of oxidative/nitrosative stress, and by the signalling function assigned to many of the microarray profile neighbours of 2310004I24Rik. Furthermore, the influence of ADPRibase-Mn on the CDP-choline or CDP-ethanolamine pathways of phospholipid biosynthesis cannot be discounted.
authors: Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, 06080 Badajoz, Spain.
authors: José
authors: J
authors: Canales
authors: Ascensión
authors: A
authors: Fernández
authors: João Meireles
authors: JM
authors: Ribeiro
authors: Alicia
authors: A
authors: Cabezas
authors: Joaquim Rui
authors: JR
authors: Rodrigues
authors: José Carlos
authors: JC
authors: Cameselle
authors: María Jesús
authors: MJ
authors: Costas
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003565:Cytidine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology; D008221:Lymphoid Tissue / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D004983:Ethanolamines; D009702:Nucleoside Diphosphate Sugars; D011994:Recombinant Proteins; D000246:Adenosine Diphosphate Ribose; C006933:CDP ethanolamine; D008345:Manganese; D003566:Cytidine Diphosphate Choline; D000244:Adenosine Diphosphate; D003565:Cytidine Diphosphate; C100068:cytidine diphosphate glycerol; C058796:ADP-ribose pyrophosphatase I; D011755:Pyrophosphatases