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Identification
HMDB Protein ID HMDBP00432
Secondary Accession Numbers
  • 5669
Name Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial
Synonyms
  1. dUTP pyrophosphatase
  2. dUTPase
Gene Name DUT
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity
Specific Function This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Pathways
  • Beta Ureidopropionase Deficiency
  • Dihydropyrimidinase Deficiency
  • dUMP biosynthesis
  • MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
  • Pyrimidine Metabolism
  • Pyrimidine metabolism
  • UMP Synthase Deficiency (Orotic Aciduria)
Reactions
Deoxyuridine triphosphate + Water → dUMP + Pyrophosphate details
GO Classification
Biological Process
pyrimidine nucleoside biosynthetic process
pyrimidine nucleobase metabolic process
DNA replication
dUMP biosynthetic process
dUTP metabolic process
Cellular Component
mitochondrion
nucleoplasm
Function
catalytic activity
hydrolase activity
nucleoside-triphosphate diphosphatase activity
dutp diphosphatase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
Molecular Function
dUTP diphosphatase activity
Process
metabolic process
nitrogen compound metabolic process
cellular nitrogen compound metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
nucleobase, nucleoside and nucleotide metabolic process
nucleoside phosphate metabolic process
nucleotide metabolic process
pyrimidine nucleoside triphosphate metabolic process
pyrimidine deoxyribonucleoside triphosphate metabolic process
dutp metabolic process
pyrimidine nucleotide metabolic process
Cellular Location
  1. Isoform 2:Nucleus
Gene Properties
Chromosome Location 15
Locus 15q21.1
SNPs DUT
Gene Sequence
>759 bp
ATGACTCCCCTCTGCCCTCGCCCCGCGCTCTGCTACCATTTCCTTACGTCTCTGCTTCGC
TCAGCGATGCAAAACGCGCGAGGCGCACGGCAGAGGGCCGAAGCCGCGGTACTCTCCGGG
CCAGGCCCGCCCCTCGGCCGCGCCGCGCAGCACGGGATTCCCCGGCCGCTGTCCAGCGCT
GGCCGCCTGAGCCAAGGCTGCCGCGGAGCCAGTACAGTCGGGGCCGCTGGCTGGAAGGGC
GAGCTTCCTAAGGCGGGGGGAAGCCCGGCGCCGGGGCCGGAGACACCCGCCATTTCACCC
AGTAAGCGGGCCCGGCCTGCGGAGGTGGGCGGCATGCAGCTCCGCTTTGCCCGGCTCTCC
GAGCACGCCACGGCCCCCACCCGGGGCTCCGCGCGCGCCGCGGGCTACGACCTGTACAGT
GCCTATGATTACACAATACCACCTATGGAGAAAGCTGTTGTGAAAACGGACATTCAGATA
GCGCTCCCTTCTGGGTGTTATGGAAGAGTGGCTCCACGGTCAGGCTTGGCTGCAAAACAC
TTTATTGATGTAGGAGCTGGTGTCATAGATGAAGATTATAGAGGAAATGTTGGTGTTGTA
CTGTTTAATTTTGGCAAAGAAAAGTTTGAAGTCAAAAAAGGTGATCGAATTGCACAGCTC
ATTTGCGAACGGATTTTTTATCCAGAAATAGAAGAAGTTCAAGCCTTGGATGACACCGAA
AGGGGTTCAGGAGGTTTTGGTTCCACTGGAAAGAATTAA
Protein Properties
Number of Residues 252
Molecular Weight 26562.975
Theoretical pI 9.368
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial
MTPLCPRPALCYHFLTSLLRSAMQNARGTAEGRSRGTLRARPAPRPPAAQHGIPRPLSSA
GRLSQGCRGASTVGAAGWKGELPKAGGSPAPGPETPAISPSKRARPAEVGGMQLRFARLS
EHATAPTRGSARAAGYDLYSAYDYTIPPMEKAVVKTDIQIALPSGCYGRVAPRSGLAAKH
FIDVGAGVIDEDYRGNVGVVLFNFGKEKFEVKKGDRIAQLICERIFYPEIEEVQALDDTE
RGSGGFGSTGKN
GenBank ID Protein 70906441
UniProtKB/Swiss-Prot ID P33316
UniProtKB/Swiss-Prot Entry Name DUT_HUMAN
PDB IDs
GenBank Gene ID NM_001025248.1
GeneCard ID DUT
GenAtlas ID DUT
HGNC ID HGNC:3078
References
General References
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  2. 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. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. Ladner RD, McNulty DE, Carr SA, Roberts GD, Caradonna SJ: Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase. J Biol Chem. 1996 Mar 29;271(13):7745-51. [PubMed:8631816 ]
  6. Cohen D, Heng HH, Shi XM, McIntosh EM, Tsui LC, Pearlman RE: Assignment of the human dUTPase gene (DUT) to chromosome 15q15-q21. 1 by fluorescence in situ hybridization. Genomics. 1997 Feb 15;40(1):213-5. [PubMed:9070952 ]
  7. McIntosh EM, Ager DD, Gadsden MH, Haynes RH: Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8020-4. [PubMed:1325640 ]
  8. Strahler JR, Zhu XX, Hora N, Wang YK, Andrews PC, Roseman NA, Neel JV, Turka L, Hanash SM: Maturation stage and proliferation-dependent expression of dUTPase in human T cells. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4991-5. [PubMed:8389461 ]
  9. Mol CD, Harris JM, McIntosh EM, Tainer JA: Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits. Structure. 1996 Sep 15;4(9):1077-92. [PubMed:8805593 ]
  10. Varga B, Barabas O, Kovari J, Toth J, Hunyadi-Gulyas E, Klement E, Medzihradszky KF, Tolgyesi F, Fidy J, Vertessy BG: Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase. FEBS Lett. 2007 Oct 2;581(24):4783-8. Epub 2007 Sep 12. [PubMed:17880943 ]