ID:DUT_HUMAN DESCRIPTION: RecName: Full=Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial; Short=dUTPase; EC=3.6.1.23; AltName: Full=dUTP pyrophosphatase; Flags: Precursor; 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. CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate. COFACTOR: Magnesium. ENZYME REGULATION: Phosphorylation is necessary for activity. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.5 uM for dUTP; Note=for both isoform 2 and isoform 3; PATHWAY: Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2. SUBUNIT: Homotrimer. INTERACTION: Q6ZVK8:NUDT18; NbExp=3; IntAct=EBI-353224, EBI-740486; SUBCELLULAR LOCATION: Isoform 2: Nucleus. SUBCELLULAR LOCATION: Isoform 3: Mitochondrion. TISSUE SPECIFICITY: Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level). PTM: Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. Phosphorylation in mature T-cells occurs in a cell cycle-dependent manner. Isoform 3 is not phosphorylated. PTM: The initiator methionine is cleaved in isoform 2. MISCELLANEOUS: Each trimer binds three substrate molecules. The ligands are bound between subunits, and for each substrate molecule, residues from adjacent subunits contribute to the binding interactions. SIMILARITY: Belongs to the dUTPase family. SEQUENCE CAUTION: Sequence=AAB71393.1; Type=Frameshift; Positions=29, 47; Sequence=AAB93866.1; Type=Frameshift; Positions=29, 47; Sequence=AAB94642.1; Type=Frameshift; Positions=29, 47; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/dut/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P33316
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006139 nucleobase-containing compound metabolic process GO:0006226 dUMP biosynthetic process GO:0006260 DNA replication GO:0009117 nucleotide metabolic process GO:0015949 nucleobase-containing small molecule interconversion GO:0046080 dUTP metabolic process GO:0046081 dUTP catabolic process
AK000629 - Homo sapiens cDNA FLJ20622 fis, clone KAT04833, highly similar to U31930 Human deoxyuridine nucleotidohydrolase mRNA. BC070339 - Homo sapiens deoxyuridine triphosphatase, mRNA (cDNA clone MGC:88344 IMAGE:3998021), complete cds. BC110377 - Homo sapiens deoxyuridine triphosphatase, mRNA (cDNA clone MGC:110970 IMAGE:5728970), complete cds. AK298464 - Homo sapiens cDNA FLJ55818 complete cds, highly similar to Homo sapiens dUTP pyrophosphatase (DUT), transcript variant 1, mRNA. U90223 - Human deoxyuridine triphosphate nucleotidohydrolase precursor mRNA, nuclear gene encoding mitochondrial protein, complete cds. AB528727 - Synthetic construct DNA, clone: pF1KB6992, Homo sapiens DUT gene for deoxyuridine triphosphatase, without stop codon, in Flexi system. KJ905194 - Synthetic construct Homo sapiens clone ccsbBroadEn_14620 DUT-like gene, encodes complete protein. AK291515 - Homo sapiens cDNA FLJ77673 complete cds, highly similar to Homo sapiens dUTP pyrophosphatase (DUT), mRNA. AK312122 - Homo sapiens cDNA, FLJ92404, Homo sapiens dUTP pyrophosphatase (DUT), mRNA. U31930 - Human deoxyuridine nucleotidohydrolase mRNA, complete cds. U62891 - Human deoxyuridine triphosphatase (DUT) mRNA, complete cds. L11877 - Homo sapiens dUTP nucleotidohydrolase mRNA, 5' end. M89913 - Human dUTP pyrophosphatase (hdut) mRNA, complete cds. AB049113 - Homo sapiens DUT mRNA for dUTP pyrophosphatase, complete cds. DQ894375 - Synthetic construct Homo sapiens clone IMAGE:100008835; FLH170025.01L; RZPDo839A1297D dUTP pyrophosphatase (DUT) gene, encodes complete protein. DQ891191 - Synthetic construct clone IMAGE:100003821; FLH170029.01X; RZPDo839A1298D dUTP pyrophosphatase (DUT) gene, encodes complete protein. KJ891075 - Synthetic construct Homo sapiens clone ccsbBroadEn_00469 DUT gene, encodes complete protein. CR541781 - Homo sapiens full open reading frame cDNA clone RZPDo834G0530D for gene DUT, dUTP pyrophosphatase; complete cds, without stopcodon. CR541720 - Homo sapiens full open reading frame cDNA clone RZPDo834B0729D for gene DUT, dUTP pyrophosphatase; complete cds, incl. stopcodon. JD495476 - Sequence 476500 from Patent EP1572962. JD495475 - Sequence 476499 from Patent EP1572962. JD491424 - Sequence 472448 from Patent EP1572962. JD519995 - Sequence 501019 from Patent EP1572962. JD374721 - Sequence 355745 from Patent EP1572962. JD313563 - Sequence 294587 from Patent EP1572962. JD243743 - Sequence 224767 from Patent EP1572962. JD115756 - Sequence 96780 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCyc Knowledge Library PWY-7184 - pyrimidine deoxyribonucleotides de novo biosynthesis PWY-7211 - superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
BioCarta from NCI Cancer Genome Anatomy Project h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)
Reactome (by CSHL, EBI, and GO)
Protein P33316 (Reactome details) participates in the following event(s):