UniProt ID: Q7ZWC3 |
FUNCTION: Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool (PubMed:26862114, PubMed:30304478). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy- dATP) into 2-oxo-dAMP (PubMed:26862114). Has also a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:26862114, PubMed:30304478). Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A (PubMed:26862114, PubMed:30304478). Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA (PubMed:32144205, PubMed:30304478). Through this antimutagenic activity protects cells from oxidative stress (PubMed:32144205, PubMed:26862114, PubMed:30304478). {ECO:0000269|PubMed:26862114, ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:32144205}. CATALYTIC ACTIVITY: Reaction=2-oxo-dATP + H2O = 2-oxo-dAMP + diphosphate + H(+); Xref=Rhea:RHEA:31583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63212, ChEBI:CHEBI:77897; EC=3.6.1.56; Evidence={ECO:0000269|PubMed:26862114}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31584; Evidence={ECO:0000305|PubMed:26862114}; CATALYTIC ACTIVITY: Reaction=2-oxo-ATP + H2O = 2-oxo-AMP + diphosphate + H(+); Xref=Rhea:RHEA:67392, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:71395, ChEBI:CHEBI:172878; Evidence={ECO:0000250|UniProtKB:P36639}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67393; Evidence={ECO:0000250|UniProtKB:P36639}; CATALYTIC ACTIVITY: Reaction=8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+); Xref=Rhea:RHEA:31575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63224, ChEBI:CHEBI:77896; Evidence={ECO:0000269|PubMed:26862114}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31576; Evidence={ECO:0000305|PubMed:26862114}; CATALYTIC ACTIVITY: Reaction=8-oxo-dATP + H2O = 8-oxo-dAMP + diphosphate + H(+); Xref=Rhea:RHEA:65396, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:71361, ChEBI:CHEBI:172871; Evidence={ECO:0000269|PubMed:30304478}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65397; Evidence={ECO:0000305|PubMed:30304478}; CATALYTIC ACTIVITY: Reaction=H2O + O(6)-methyl-dGTP = diphosphate + H(+) + O(6)-methyl- dGMP; Xref=Rhea:RHEA:67600, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:169974, ChEBI:CHEBI:169975; Evidence={ECO:0000269|PubMed:30304478}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67601; Evidence={ECO:0000305|PubMed:30304478}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-methyl-dATP = diphosphate + H(+) + N(6)-methyl- dAMP; Xref=Rhea:RHEA:67604, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:169976, ChEBI:CHEBI:172872; Evidence={ECO:0000269|PubMed:32144205}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67605; Evidence={ECO:0000269|PubMed:32144205}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-methyl-ATP = diphosphate + H(+) + N(6)-methyl-AMP; Xref=Rhea:RHEA:67608, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:144842, ChEBI:CHEBI:172873; Evidence={ECO:0000250|UniProtKB:P36639}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67609; Evidence={ECO:0000250|UniProtKB:P36639}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:30304478, ECO:0007744|PDB:5OTN}; Note=Binds 2 Mg(2+) ion per subunit. {ECO:0000269|PubMed:30304478, ECO:0007744|PDB:5OTN}; ACTIVITY REGULATION: Inhibited by TH588. {ECO:0000269|PubMed:26862114}. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3.9 uM for 8-oxo-dGTP (at pH 7.5) {ECO:0000269|PubMed:26862114}; KM=6.1 uM for 2-oxo-dATP (at pH 7.5) {ECO:0000269|PubMed:26862114}; KM=91.4 uM for dGTP (at pH 7.5) {ECO:0000269|PubMed:26862114}; Note=kcat is 5.4 sec(-1) with 8-oxo-dGTP as substrate (at pH 7.5) (PubMed:26862114). kcat is 12.0 sec(-1) with 2-oxo-dATP as substrate (at pH 7.5) (PubMed:26862114). kcat is 7.6 sec(-1) with dGTP as substrate (at pH 7.5) (PubMed:26862114). Shows the best catalytic efficiency for the 8-oxo-dGTP substrate (PubMed:26862114). {ECO:0000269|PubMed:26862114}; SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P36639}. SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P36639}. Mitochondrion matrix {ECO:0000250|UniProtKB:P36639}. Nucleus {ECO:0000250|UniProtKB:P36639}. SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}. |
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