Description: Homo sapiens deoxyuridine triphosphatase (DUT), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA. RefSeq Summary (NM_001025248): This gene encodes an essential enzyme of nucleotide metabolism. The encoded protein forms a ubiquitous, homotetrameric enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This reaction serves two cellular purposes: providing a precursor (dUMP) for the synthesis of thymine nucleotides needed for DNA replication, and limiting intracellular pools of dUTP. Elevated levels of dUTP lead to increased incorporation of uracil into DNA, which induces extensive excision repair mediated by uracil glycosylase. This repair process, resulting in the removal and reincorporation of dUTP, is self-defeating and leads to DNA fragmentation and cell death. Alternative splicing of this gene leads to different isoforms that localize to either the mitochondrion or nucleus. A related pseudogene is located on chromosome 19. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr15:48,623,621-48,635,570 Size: 11,950 Total Exon Count: 7 Strand: + Coding Region Position: hg19 chr15:48,623,713-48,634,275 Size: 10,563 Coding Exon Count: 7
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/";
Adiponectin David Melzer et al. PLoS genetics 2008, A genome-wide association study identifies protein quantitative trait loci (pQTLs)., PLoS genetics.
[PubMed 18464913]
protein quantitative trait loci Melzer ,et al. 2008, A Genome-Wide Association Study Identifies Protein Quantitative Trait Loci (pQTLs), PLoS genetics 2008 4- 5 : e1000072.
[PubMed 18464913]
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
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
