NUDT1

Nudix (nucleoside diphosphate linked moiety X)-type motif 1
PDB rendering based on 1iry.
Available structures PDB 1iry
Identifiers
Symbols	NUDT1; MTH1
External IDs	OMIM: 600312 MGI: 109280 HomoloGene: 1839 GeneCards: NUDT1 Gene
EC number	3.1.6.-
Gene Ontology Molecular function • GTPase activity • protein binding • 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity • hydrolase activity • 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity • metal ion binding Cellular component • cytoplasm Biological process • GTP catabolic process • purine nucleotide catabolic process • DNA repair • response to oxidative stress • DNA protection Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4521	17766
Ensembl	ENSG00000106268	ENSMUSG00000036639
UniProt	P36639	Q542J4
RefSeq (mRNA)	NM_002452.3	NM_008637.1
RefSeq (protein)	NP_002443.3	NP_032663.1
Location (UCSC)	Chr 7: 2.28 – 2.29 Mb	Chr 5: 140.81 – 140.81 Mb
PubMed search	[1]	[2]

7,8-dihydro-8-oxoguanine triphosphatase is an enzyme that in humans is encoded by the NUDT1 gene.^[1][2][3]

Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described.^[3]

References

1. ^ Ponnambalam S, Jackson AP, LeBeau MM, Pravtcheva D, Ruddle FH, Alibert C, Parham P (May 1995). "Chromosomal location and some structural features of human clathrin light-chain genes (CLTA and CLTB)". Genomics 24 (3): 440–4. doi:10.1006/geno.1994.1650. PMID 7713494. 
2. ^ Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, Sekiguchi M (Nov 1993). "Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis". J Biol Chem 268 (31): 23524–30. PMID 8226881. 
3. ^ ^{a b} "Entrez Gene: NUDT1 nudix (nucleoside diphosphate linked moiety X)-type motif 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4521. 

Further reading

• Furuichi M, Yoshida MC, Oda H, et al. (1995). "Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion.". Genomics 24 (3): 485–90. doi:10.1006/geno.1994.1657. PMID 7713500. 
• Kang D, Nishida J, Iyama A, et al. (1995). "Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria.". J. Biol. Chem. 270 (24): 14659–65. doi:10.1074/jbc.270.24.14659. PMID 7782328. 
• Oda H, Nakabeppu Y, Furuichi M, Sekiguchi M (1997). "Regulation of expression of the human MTH1 gene encoding 8-oxo-dGTPase. Alternative splicing of transcription products.". J. Biol. Chem. 272 (28): 17843–50. doi:10.1074/jbc.272.28.17843. PMID 9211940. 
• Oda H, Taketomi A, Maruyama R, et al. (1999). "Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism.". Nucleic Acids Res. 27 (22): 4335–43. doi:10.1093/nar/27.22.4335. PMC 148714. PMID 10536140. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=148714. 
• Tsuzuki T, Egashira A, Igarashi H, et al. (2001). "Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase.". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11456–61. doi:10.1073/pnas.191086798. PMC 58751. PMID 11572992. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=58751. 
• Sakai Y, Furuichi M, Takahashi M, et al. (2002). "A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1.". J. Biol. Chem. 277 (10): 8579–87. doi:10.1074/jbc.M110566200. PMID 11756418. 
• Fujikawa K, Yakushiji H, Nakabeppu Y, et al. (2002). "8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog.". FEBS Lett. 512 (1–3): 149–51. doi:10.1016/S0014-5793(02)02240-8. PMID 11852070. 
• Topp H, Armbrust S, Lengger C, et al. (2002). "Renal excretion of 8-oxo-7,8-dihydro-2(')-deoxyguanosine: degradation rates of RNA and metabolic rate in humans". Arch. Biochem. Biophys. 402 (1): 31–7. doi:10.1016/S0003-9861(02)00034-6. PMID 12051680. 
• Takahashi M, Maraboeuf F, Sakai Y, et al. (2002). "Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein". J. Mol. Biol. 319 (1): 129–39. doi:10.1016/S0022-2836(02)00163-8. PMID 12051941. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Liu Z, Wang LE, Strom SS, et al. (2003). "Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case-control analysis". Mol. Carcinog. 36 (3): 123–9. doi:10.1002/mc.10108. PMID 12619034. 
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961. 
• Ishibashi T, Hayakawa H, Sekiguchi M (2004). "A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides". EMBO Rep. 4 (5): 479–83. doi:10.1038/sj.embor.embor838. PMC 1319193. PMID 12717453. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1319193. 
• Kennedy CH, Pass HI, Mitchell JB (2004). "Expression of human MutT homologue (hMTH1) protein in primary non-small-cell lung carcinomas and histologically normal surrounding tissue". Free Radic. Biol. Med. 34 (11): 1447–57. doi:10.1016/S0891-5849(03)00176-X. PMID 12757855. 
• Yoshimura D, Sakumi K, Ohno M, et al. (2003). "An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress". J. Biol. Chem. 278 (39): 37965–73. doi:10.1074/jbc.M306201200. PMID 12857738. 
• Kamiya H, Dugué L, Yakushiji H, et al. (2003). "Substrate recognition by the human MTH1 protein". Nucleic Acids Res. Suppl. (2): 85–6. PMID 12903117. 
• Bialkowski K, Kasprzak KS (2004). "Inhibition of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity of the antimutagenic human MTH1 protein by nucleoside 5'-diphosphates". Free Radic. Biol. Med. 35 (6): 595–602. doi:10.1016/S0891-5849(03)00362-9. PMID 12957652. 
• Kamiya H, Yakushiji H, Dugué L, et al. (2004). "Probing the substrate recognition mechanism of the human MTH1 protein by nucleotide analogs". J. Mol. Biol. 336 (4): 843–50. doi:10.1016/j.jmb.2003.12.060. PMID 15095864.