Nucleotide triphosphate diphosphatase NUDT15

Details

Name
Nucleotide triphosphate diphosphatase NUDT15
Kind
protein
Synonyms
  • 3.6.1.9
  • MTH2
  • MutT homolog 2
  • Nucleoside diphosphate-linked moiety X motif 15
  • Nucleoside diphosphate-linked to another moiety X hydrolase 15
  • Nudix hydrolase 15
  • Nudix motif 15
Gene Name
NUDT15
UniProtKB Entry
Q9NV35Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0052203|Nucleotide triphosphate diphosphatase NUDT15
MTASAQPRGRRPGVGVGVVVTSCKHPRCVLLGKRKGSVGAGSFQLPGGHLEFGETWEECA
QRETWEEAALHLKNVHFASVVNSFIEKENYHYVTILMKGEVDVTHDSEPKNVEPEKNESW
EWVPWEELPPLDQLFWGLRCLKEQGYDPFKEDLNHLVGYKGNHL
Number of residues
164
Molecular Weight
18608.965
Theoretical pI
Not Available
GO Classification
Functions
8-oxo-dGDP phosphatase activity / nucleoside triphosphate diphosphatase activity
Processes
nucleobase-containing small molecule metabolic process / xenobiotic catabolic process
General Function
May catalyze the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:26238318). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:22556419, PubMed:26238318). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:25108385, PubMed:26238318). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity)
Specific Function
8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0052204|Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)
ATGACGGCCAGCGCACAGCCGCGCGGGCGGCGGCCAGGAGTCGGAGTCGGAGTCGTGGTG
ACCAGCTGCAAGCATCCGCGTTGCGTCCTCCTGGGGAAGAGGAAAGGCTCGGTTGGAGCT
GGCAGTTTCCAACTCCCTGGAGGTCATCTGGAGTTCGGTGAAACCTGGGAAGAATGTGCT
CAAAGGGAAACCTGGGAAGAAGCAGCTCTTCACCTGAAAAATGTTCACTTTGCCTCAGTT
GTGAATTCTTTCATTGAGAAGGAGAATTACCATTATGTTACTATATTAATGAAAGGAGAA
GTGGATGTGACTCATGATTCAGAACCAAAGAATGTAGAGCCTGAAAAAAATGAAAGTTGG
GAGTGGGTTCCTTGGGAAGAACTACCTCCCCTGGACCAGCTTTTCTGGGGACTGCGTTGT
TTAAAAGAACAAGGCTATGATCCATTTAAAGAAGATCTGAACCATCTGGTGGGATACAAA
GGAAATCATCTCTAG
Chromosome Location
13
Locus
13q14.2
External Identifiers
ResourceLink
UniProtKB IDQ9NV35
UniProtKB Entry NameNUD15_HUMAN
GeneCard IDNUDT15
HGNC IDHGNC:23063
PDB ID(s)5BON, 5LPG, 6T5J, 7AOM, 7AOP, 7B63, 7B64, 7B65, 7B66, 7B67, 7B7V, 7NR6, 7R0D
KEGG IDhsa:55270
NCBI Gene ID55270
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Bessman MJ, Frick DN, O'Handley SF: The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes. J Biol Chem. 1996 Oct 11;271(41):25059-62. doi: 10.1074/jbc.271.41.25059. [Article]
  5. Yu Y, Cai JP, Tu B, Wu L, Zhao Y, Liu X, Li L, McNutt MA, Feng J, He Q, Yang Y, Wang H, Sekiguchi M, Zhu WG: Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2. J Biol Chem. 2009 Jul 17;284(29):19310-20. doi: 10.1074/jbc.M109.015289. Epub 2009 May 6. [Article]
  6. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  7. Takagi Y, Setoyama D, Ito R, Kamiya H, Yamagata Y, Sekiguchi M: Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. J Biol Chem. 2012 Jun 15;287(25):21541-9. doi: 10.1074/jbc.M112.363010. Epub 2012 May 3. [Article]
  8. Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, Haritunians T, Ye BD, Kim KJ, Park SH, Park SK, Yang DH, Dubinsky M, Lee I, McGovern DP, Liu J, Song K: A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014 Sep;46(9):1017-20. doi: 10.1038/ng.3060. Epub 2014 Aug 10. [Article]
  9. Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, Lin TN, Hoshitsuki K, Nersting J, Kihira K, Hofmann U, Komada Y, Kato M, McCorkle R, Li L, Koh K, Najera CR, Kham SK, Isobe T, Chen Z, Chiew EK, Bhojwani D, Jeffries C, Lu Y, Schwab M, Inaba H, Pui CH, Relling MV, Manabe A, Hori H, Schmiegelow K, Yeoh AE, Evans WE, Yang JJ: NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet. 2016 Apr;48(4):367-73. doi: 10.1038/ng.3508. Epub 2016 Feb 15. [Article]
  10. Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Bostrom J, Warpman Berglund U, Helleday T, Stenmark P: Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2. Nat Commun. 2015 Aug 4;6:7871. doi: 10.1038/ncomms8871. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
AzathioprineapprovedunknownenzymesubstrateDetails