NUDT1 (7p22.3) MTH1 (8-oxodGTPase) (2-OH-dATPdiphosphatase)

NUDIX1
https://www.ncbi.nlm.nih.gov/gene/4521

Also known as

MTH1

Summary

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. [provided by RefSeq, Jul 2008]

Expression

Broad expression in bone marrow (RPKM 17.0), testis (RPKM 13.9) and 24 other tissues See more

Preferred Names

7,8-dihydro-8-oxoguanine triphosphatase

Names

2-hydroxy-dATP diphosphatase

8-oxo-7,8-dihydrodeoxyguanosine triphosphatase

8-oxo-7,8-dihydroguanosine triphosphatase

8-oxo-dGTPase

mutT human homolog 1

nucleoside diphosphate-linked moiety X motif 1

nucleoside diphosphate-linked moiety X-type motif 1

nudix (nucleoside diphosphate linked moiety X)-type motif 1

nudix motif 1

NP_002443.3

• EC 3.6.1.55

• EC 3.6.1.56

Structure, History  , many isoforms.
Ex. isoform p18,  https://www.ncbi.nlm.nih.gov/protein/NP_945188.1
1994:  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. 

Conserved Domains (1) summary

cd03427
Location:6 → 140

MTH1; MutT homolog-1 (MTH1) is a member of the Nudix hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the ...

Related articles in PubMed

1. hMTH1 is required for maintaining migration and invasion potential of human thyroid cancer cells. Arczewska KD, et al. DNA Repair (Amst), 2018 Sep. PMID 30055508
2. MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good? Abbas HHK, et al. BMC Cancer, 2018 Apr 16. PMID 29661172, Free PMC Article
3. (S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1. Dai X, et al. J Exp Clin Cancer Res, 2017 Sep 7. PMID 28882182, Free PMC Article
4. Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer. Fujishita T, et al. Lung Cancer, 2017 Jul. PMID 28577950
5. Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity. Waz S, et al. J Biol Chem, 2017 Feb 17. PMID 28035004, Free PMC Article

See all (98) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. overall our cell viability data indicates that targeting MTH1 will likely not be an across-the-board effective non-small cell lung cancer therapeutic strategy; rather it induces non-cytotoxic DNA damage that could promote cancer heterogeneity and evolution.
2. MTH1 is required for maintaining migration and invasion potential of human thyroid cancer cells.
3. PRDX1 and MTH1 cooperate to prevent accumulation of oxidized guanine in the genome
4. Results provide evidence that MTH1 is not essential for cancer cell survival.
5. CDT1, MCM7, and NUDT1 were shown to be up-regulated in hepatocellular carcinoma tissues and provide a more accurate diagnosis than alpha-fetal protein alone.
6. Our results reveal a novel antitumor mechanism of (S)-crizotinib in NSCLC which involves activation of ROS-dependent ER stress apoptotic pathway and is independent of MTH1 inhibition
7. this study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival
8. method for predicting individual residue contributions to enzyme specificity and binding-site energies, and its application to MTH1.
9. Data indicate the specificity of the enzyme 8-oxo-dGTPase MTH1 toward the substrate 8-oxo-dGTP.
10. We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.