NUDT1 hydrolyzes N6-methyl-ATP to N6-methyl-AMP

Stable Identifier
R-HSA-9731632
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
N6-methyl-ATP + H2O = diphosphate + H+ + N6-methyl-AMP
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NUDT1 (MTH1) catalyzes the reaction of N6-methyl-ATP and water to form N6-methyl-AMP and PPi (pyrophosphate) (Scaletti et al. 2020). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been shown to be enzymatically active as a monomer associated with a magnesium ion (Mishima et al. 2004; Sakumi et al. 1993; Takagi et al. 2012). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). While NUDT1 acts less efficiently on N6-methyl-ATP than on N6-methyl-dATP, the intracellular concentration of the latter molecule is likely much greater, consistent with a physiological role for this reaction (Scaletti et al. 2020).

Literature References
PubMed ID Title Journal Year
15133035 Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates

Mishima, M, Sakai, Y, Itoh, N, Kamiya, H, Furuichi, M, Takahashi, M, Yamagata, Y, Iwai, S, Nakabeppu, Y, Shirakawa, M

J. Biol. Chem. 2004
32144205 MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool

Scaletti, ER, Vallin, KS, Bräutigam, L, Sarno, A, Warpman Berglund, U, Helleday, T, Stenmark, P, Jemth, AS

J Biol Chem 2020
22556419 Human MTH3 (NUDT18) Protein Hydrolyzes Oxidized Forms of Guanosine and Deoxyguanosine Diphosphates: COMPARISON WITH MTH1 AND MTH2

Takagi, Y, Setoyama, D, Ito, R, Kamiya, H, Yamagata, Y, Sekiguchi, M

J. Biol. Chem. 2012
10536140 Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism

Oda, H, Taketomi, A, Maruyama, R, Itoh, R, Nishioka, K, Yakushiji, H, Suzuki, T, Sekiguchi, M, Nakabeppu, Y

Nucleic Acids Res. 1999
7782328 Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria

Kang, D, Nishida, J, Iyama, A, Nakabeppu, Y, Furuichi, M, Fujiwara, T, Sekiguchi, M, Takeshige, K

J. Biol. Chem. 1995
8226881 Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis

Sakumi, K, Furuichi, M, Tsuzuki, T, Kakuma, T, Kawabata, S, Maki, H, Sekiguchi, M

J. Biol. Chem. 1993
Participants
Participates
Catalyst Activity

hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides of NUDT1 [cytosol]

Orthologous Events
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