ID:NUDT3_HUMAN DESCRIPTION: RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 1; Short=DIPP-1; EC=3.6.1.52; AltName: Full=Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1; EC=3.6.1.-; AltName: Full=Nucleoside diphosphate-linked moiety X motif 3; Short=Nudix motif 3; FUNCTION: 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 hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and 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. CATALYTIC ACTIVITY: Diphospho-myo-inositol polyphosphate + H(2)O = myo-inositol polyphosphate + phosphate. COFACTOR: Binds 3 magnesium ions per subunit. ENZYME REGULATION: Inhibited by fluoride and InsP6. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.9 uM for Ap6A; KM=7.7 uM for Ap5A; KM=38 mM for 5-phosphoribose 1-diphosphate; KM=4.2 nM for PP-InsP5; pH dependence: Optimum pH is 7-7.5; SUBUNIT: Monomer (By similarity). SUBCELLULAR LOCATION: Cytoplasm (Probable). TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in brain, heart, pancreas and liver. Also expressed in placenta, lung and kidney. SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily. SIMILARITY: Contains 1 nudix hydrolase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95989
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AF062529 - Homo sapiens clone 486790 diphosphoinositol polyphosphate phosphohydrolase mRNA, complete cds. BC007727 - Homo sapiens nudix (nucleoside diphosphate linked moiety X)-type motif 3, mRNA (cDNA clone MGC:12752 IMAGE:4303483), complete cds. AF062530 - Homo sapiens clone 469920 diphosphoinositol polyphosphate phosphohydrolase mRNA, complete cds. AK313440 - Homo sapiens cDNA, FLJ93979, Homo sapiens nudix (nucleoside diphosphate linked moiety X)-type motif 3 (NUDT3), mRNA. KJ893244 - Synthetic construct Homo sapiens clone ccsbBroadEn_02638 NUDT3 gene, encodes complete protein. BT019984 - Homo sapiens nudix (nucleoside diphosphate linked moiety X)-type motif 3 mRNA, complete cds. BT019985 - Homo sapiens nudix (nucleoside diphosphate linked moiety X)-type motif 3 mRNA, complete cds. DQ893118 - Synthetic construct clone IMAGE:100005748; FLH193906.01X; RZPDo839D0479D nudix (nucleoside diphosphate linked moiety X)-type motif 3 (NUDT3) gene, encodes complete protein. DQ896391 - Synthetic construct Homo sapiens clone IMAGE:100010851; FLH193902.01L; RZPDo839D0469D nudix (nucleoside diphosphate linked moiety X)-type motif 3 (NUDT3) gene, encodes complete protein. AB463951 - Synthetic construct DNA, clone: pF1KB6839, Homo sapiens NUDT3 gene for nudix (nucleoside diphosphate linked moiety X)-type motif 3, without stop codon, in Flexi system. AF052101 - Homo sapiens clone 23872 mRNA sequence. AK025515 - Homo sapiens cDNA: FLJ21862 fis, clone HEP02321, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence. AK026168 - Homo sapiens cDNA: FLJ22515 fis, clone HRC12122, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence. DQ572964 - Homo sapiens piRNA piR-41076, complete sequence. DQ597651 - Homo sapiens piRNA piR-35717, complete sequence. DQ601646 - Homo sapiens piRNA piR-39712, complete sequence. AK025759 - Homo sapiens cDNA: FLJ22106 fis, clone HEP17675. JD118479 - Sequence 99503 from Patent EP1572962. JD388417 - Sequence 369441 from Patent EP1572962. JD041438 - Sequence 22462 from Patent EP1572962. JD274902 - Sequence 255926 from Patent EP1572962. JD274901 - Sequence 255925 from Patent EP1572962. JD496998 - Sequence 478022 from Patent EP1572962. BC043178 - Homo sapiens cDNA clone IMAGE:5287836. AK057088 - Homo sapiens cDNA FLJ32526 fis, clone SMINT2000073. JD537705 - Sequence 518729 from Patent EP1572962. JD546953 - Sequence 527977 from Patent EP1572962. DQ591995 - Homo sapiens piRNA piR-59107, complete sequence. JD083206 - Sequence 64230 from Patent EP1572962. JD117312 - Sequence 98336 from Patent EP1572962. JD518063 - Sequence 499087 from Patent EP1572962. JD199555 - Sequence 180579 from Patent EP1572962. JD038754 - Sequence 19778 from Patent EP1572962. DQ573515 - Homo sapiens piRNA piR-41627, complete sequence. JD475836 - Sequence 456860 from Patent EP1572962. JD516695 - Sequence 497719 from Patent EP1572962. JD338187 - Sequence 319211 from Patent EP1572962. JD365859 - Sequence 346883 from Patent EP1572962. JD432326 - Sequence 413350 from Patent EP1572962. JD437073 - Sequence 418097 from Patent EP1572962. JD508523 - Sequence 489547 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O95989 (Reactome details) participates in the following event(s):
R-HSA-1855165 (PP)2-IP4 is dephosphorylated to 5-PP-IP5 by NUDT(1) in the cytosol R-HSA-2023973 (PP)2-IP4 is dephosphorylated to 1/3-PP-IP5 by NUDT(1) in the cytosol R-HSA-1855198 5-PP-IP5 is dephosphorylated to IP6 by NUDT(1) in the cytosol R-HSA-2023971 1/3 PP-IP5 is dephosphorylated to IP6 by NUDT(1) in the cytosol R-HSA-1855167 Synthesis of pyrophosphates in the cytosol R-HSA-1483249 Inositol phosphate metabolism R-HSA-1430728 Metabolism