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

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

Stable Identifier

R-HSA-9731632

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

N(6)-methyl-ATP + H2O => N(6)-methyl-AMP + diphosphate + H(+)

ReviewStatus

5/5

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NUDT1 hydrolyzes N6-methyl-ATP to 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
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
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
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