The reference OMIM entry for this protein is 600312

Nucleoside diphosphate-linked moiety x motif 1; nudt1
Nudix motif 1
Mutt homolog 1; mth1
8-@oxo-7,8-dihydroguanosine triphosphatase

DESCRIPTION

Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is most important because of its abundance and mutagenicity. The product of the MTH1 gene hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool, thereby preventing occurrence of transversion mutations (summary by Tsuzuki et al., 2001).

CLONING

Sakumi et al. (1993) purified NUDT1 from Jurkat human T cells. By sequencing peptide fragments, followed by PCR analysis of Jurkat and HeLa cell cDNA libraries, they cloned full-length NUDT1. The deduced protein contains 156 amino acids and has a calculated molecular mass of approximately 17.9 kD. It has a 24-amino acid motif similar to the central catalytic region of E. coli mutT. Gel-filtration analysis detected NUDT1 at a position corresponding to 18 kD. By sequencing MTH1 clones obtained from Jurkat cells, Oda et al. (1997) identified 7 MTH1 variants that differ in splicing of exons 1 and 2 and that contain different AUG translational start codons. The major variant, which contains exon 1a and lacks exon 2, was predicted to encode an 18-kD protein. Northern blot analysis detected a 0.8-kb MTH1 transcript variably expressed in most of the 21 tissues and 2 cell lines examined. Highest expression was detected in Jurkat cells, followed by testis, thymus, and HeLa cells. Western blot analysis detected multiple MTH1 proteins in crude extracts from various human cell lines. A fraction of MTH1 existed in the mitochondrial matrix. By Western blot analysis of in vitro-translated protein, Oda et al. (1999) found that the 7 main MTH1 splice variants encoded proteins with apparent molecular masses of 22, 21, and 18 kD. A polymorphic alteration (GU-to-GC) at the beginning of exon 2c converts an in-frame UGA to CGA, yielding another UGA further upstream and producing an additional polypeptide of 26 kD. The MTH1 isoforms have unique N-terminal sequences, but they all contain the catalytic Nudix motif.

GENE STRUCTURE

Furuichi et al. (1994) isolated the genomic sequence encoding NUDT1, which they called MTH1. They determined that the NUDT1 gene is composed of at least 4 exons and spans approximately 9 kb. Igarashi et al. (1997) showed that the mouse Mth1 gene consists of 5 exons spanning about 6 kb of genomic DNA; the first 2 exons are noncoding. The authors confirmed that the human gene contains 4 exons, the first of which is noncoding. Oda et al. (1997) determined that the NUDT1 gene contains 5 major exons. There are 2 contiguous alternative sequences of exon 1 (1a and 1b) and 3 contiguous alternative segments of exon 2 (2a, 2b, and 2c). Most NUDT1 transcripts have 3 alternative translational start sites, and a SNP introduces an additional translational start site. The 5-prime upstream region lacks TATA or CCAAT sequences, but it is highly GC rich and has potential SP1 (189906)-binding sites. NUDT1 also has potential binding sites for ETS family proteins (see 164720).

MAPPING

By fluorescence in situ hybridization, Furuichi et al. (1994) mapped the NUDT1 gene to chromosome 7p22.

GENE FUNCTION

E. coli cells deleted from the mutT gene have an elevated mutation frequently compared to wildtype cells. Sakumi et al. (1993) found that expression of human NUDT1 in mutT-negative E. coli increased 8-oxo-dGTPase activity an ... More on the omim web site

Subscribe to this protein entry history

Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 600312 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).