DUT encodes deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase; dUTP pyrophosphatase; EC 3.6.1.23), a Mg2+-dependent hydrolase that cleaves dUTP into dUMP and inorganic diphosphate. Through this single reaction the enzyme performs a dual, complementary role in pyrimidine deoxyribonucleotide metabolism: it keeps the intracellular dUTP:dTTP ratio low, preventing uracil misincorporation into DNA (and the resulting futile base-excision-repair cycles and DNA strand breaks), and it produces dUMP, the substrate that thymidylate synthase methylates to dTMP during de novo thymidylate biosynthesis. The active enzyme is a homotrimer whose substrate sites are formed at subunit interfaces, with catalytic residues contributed by all three subunits. In humans, alternative splicing of the N-terminus yields a nuclear isoform (DUT-N) and a mitochondrion-targeted isoform (DUT-M) bearing a cleavable transit peptide, so that dUTPase activity is provided in both the nucleus/cytosol and the mitochondrion. The nuclear isoform is cell-cycle regulated, peaking with DNA replication. dUTPase is essential for genome integrity; biallelic loss-of-function variants cause a bone marrow failure and diabetes mellitus syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004170 dUTP diphosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred dUTP diphosphatase (dUTPase) activity. This is the well-established, experimentally confirmed core molecular function of DUT and is supported at multiple levels of evidence. Reason: dUTP diphosphatase activity is the defining, experimentally proven function of human dUTPase, confirmed by kinetics and crystal structures of the substrate/Mg2+ complex. The IBA is consistent with the direct experimental annotations and with the dUTPase family assignment. Supporting Evidence: PMID:8805593 dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. file:human/DUT/DUT-uniprot.txt Belongs to the dUTPase family |
| GO:0000287 magnesium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred magnesium ion binding. dUTPase is a Mg2+-dependent enzyme; the catalytic reaction requires a bound Mg2+ ion, confirmed in the crystal structures. Reason: Mg2+ is an experimentally confirmed cofactor of human dUTPase (UniProt COFACTOR, from PubMed:8805593), and structures were solved as the enzyme:substrate:Mg complex. The IBA is well supported. Supporting Evidence: PMID:17880943 We determined the crystal structure of the enzyme:alpha,beta-imino-dUTP:Mg complex |
| GO:0006226 dUMP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred involvement in dUMP biosynthesis. Hydrolysis of dUTP by dUTPase is the direct source of dUMP, the immediate precursor of dTMP. Reason: dUMP is the direct product of the dUTPase reaction and the substrate for thymidylate synthase; this is a core biological role of DUT and is captured by UniPathway "dUMP biosynthesis; dUMP from dCTP (dUTP route)". Supporting Evidence: PMID:8805593 dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. file:human/DUT/DUT-uniprot.txt Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP |
| GO:0046081 dUTP catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred involvement in dUTP catabolism. The dUTPase reaction is the catabolic step that removes dUTP from the deoxyribonucleotide pool. Reason: dUTP catabolism (hydrolysis of dUTP) is exactly what dUTPase does; this is a core biological-process framing of the enzymatic activity and is well supported. Supporting Evidence: PMID:15322254 dUTPase, which eliminates dUTP from the DNA biosynthetic pathway, opposes uracil misincorporation |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic transfer of magnesium ion binding from the dUTPase InterPro signature (IPR008181). Consistent with the experimentally confirmed Mg2+ cofactor. Reason: The InterPro-based IEA reproduces the experimentally validated Mg2+ dependence of dUTPase and is redundant with, and consistent with, the IBA magnesium ion binding annotation. Supporting Evidence: PMID:8805593 The dUTPase nucleotide-binding sites incorporate some features of other nucleotide-binding proteins |
| GO:0004170 dUTP diphosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined-method electronic annotation of dUTP diphosphatase activity (ARBA / EC:3.6.1.23 / RHEA:10248 / InterPro). Matches the experimentally proven function. Reason: This IEA reproduces the core, experimentally confirmed enzymatic activity of DUT and is fully consistent with the EXP/IDA/IBA annotations for the same term. Supporting Evidence: PMID:8805593 dUTPase hydrolyzes dUTP to dUMP and pyrophosphate |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt Subcellular-Location keyword mapping to nucleus, corresponding to the nuclear isoform (DUT-N / isoform 2). Reason: Nuclear localization of the nuclear isoform is experimentally established (PubMed:8631816), so this SubCell-derived IEA is correct. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt Subcellular-Location keyword mapping to mitochondrion, corresponding to the mitochondrial isoform (DUT-M / isoform 3) with its N-terminal transit peptide. Reason: Mitochondrial localization of the DUT-M isoform is experimentally established (PubMed:8631816) and independently supported by high-confidence mitochondrial proteomics; this SubCell-derived IEA is correct. Supporting Evidence: PMID:8631816 the higher molecular weight species (DUT-M) fractionates with the mitochondria |
| GO:0006226 dUMP biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined-method electronic annotation to dUMP biosynthetic process, mirroring the IBA involvement. dUMP is the direct product of dUTPase. Reason: Correct and redundant with the IBA dUMP biosynthesis annotation; dUMP is the immediate product of the dUTPase reaction. Supporting Evidence: file:human/DUT/DUT-uniprot.txt Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP |
| GO:0009177 pyrimidine deoxyribonucleoside monophosphate biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA electronic annotation to a broader parent process (pyrimidine deoxyribonucleoside monophosphate biosynthesis). This generalizes the specific dUMP biosynthetic process role. Reason: Not wrong (dUMP is a pyrimidine deoxyribonucleoside monophosphate), but this ARBA IEA is less precise than the dedicated GO:0006226 dUMP biosynthetic process term already annotated; the specific term better captures DUT's role. Supporting Evidence: file:human/DUT/DUT-uniprot.txt Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP |
| GO:0009221 pyrimidine deoxyribonucleotide biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA electronic annotation to a broad pyrimidine deoxyribonucleotide biosynthetic process. dUTPase supplies dUMP that feeds dTMP/dTTP biosynthesis. Reason: Directionally correct as DUT feeds pyrimidine deoxyribonucleotide (dTMP/dTTP) biosynthesis by providing dUMP, but this is a broad parent term less precise than the specific dUMP biosynthetic process / dTMP biosynthetic process annotations already present. Supporting Evidence: PMID:8805593 providing the dUMP for dTTP biosynthesis |
| GO:0046081 dUTP catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined-method electronic annotation to dUTP catabolic process, mirroring the IBA involvement. Reason: Correct and redundant with the IBA dUTP catabolic process annotation; hydrolysis of dUTP is the catabolic reaction catalyzed by dUTPase. Supporting Evidence: PMID:15322254 dUTPase, which eliminates dUTP from the DNA biosynthetic pathway |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interaction (with NUDT18, Q6ZVK8) captured in a proteome-scale high-throughput yeast two-hybrid interactome map. "protein binding" is uninformative and does not describe a characterized molecular function of DUT. Reason: Per curation guidelines, bare "protein binding" is uninformative. This is a high-throughput Y2H interactome hit (with NUDT18) with no established functional consequence for dUTPase. Retained (not removed) as an experimental IPI but marked as over-annotated because it does not capture a core molecular function. Supporting Evidence: PMID:16189514 we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | MARK AS OVER ANNOTATED | Summary: Second IntAct-curated binary interaction record (with NUDT18, Q6ZVK8) from the empirical binary interactome-mapping framework study. Again bare "protein binding". Reason: Bare "protein binding" from a high-throughput binary interactome study; not an informative molecular function for DUT. Retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:19060904 we predict that the entire human interactome, excluding splice variant complexity, contains approximately 74,000-200,000 binary biophysical interactions |
| GO:0001889 liver development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-Compara electronic transfer from the rat ortholog (P70583). There is no human evidence that dUTPase has a specific role in liver development; this is a peripheral, ortholog-projected annotation. Reason: dUTPase is a ubiquitous housekeeping nucleotide-metabolism enzyme; "liver development" is an over-specific ortholog-projected process not reflecting DUT's core function. Marked over-annotated rather than removed, since it derives from an experimentally verified rat annotation transferred by Ensembl. Supporting Evidence: PMID:1325640 All of these mRNAs are present in a variety of human tissues |
| GO:0030547 signaling receptor inhibitor activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-Compara electronic transfer from the rat ortholog. Reflects the reported "By similarity" moonlighting property in which dUTPase can inhibit PPAR by binding its N-terminus and blocking PPAR:RXR dimerization. Reason: This corresponds to a peripheral moonlighting activity (PPAR inhibition) inferred by similarity, not the core enzymatic function of DUT, and it derives from an ortholog projection rather than direct human evidence. Not core; marked over-annotated rather than removed. Supporting Evidence: file:human/DUT/DUT-uniprot.txt preventing the latter's dimerization with retinoid X receptor |
| GO:0032556 pyrimidine deoxyribonucleotide binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-Compara electronic transfer of pyrimidine deoxyribonucleotide binding. dUTPase does bind the pyrimidine deoxyribonucleotide dUTP as its substrate. Reason: Correct: dUTPase specifically binds the pyrimidine deoxyribonucleotide dUTP (structurally characterized substrate binding), consistent with this term. Supporting Evidence: PMID:8805593 complexes with the uracil-containing deoxyribonucleotides, dUMP, dUDP and dUTP |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-Compara electronic transfer of identical protein binding, consistent with dUTPase functioning as a homotrimer (self-association). Reason: dUTPase is an obligate homotrimer, so "identical protein binding" is factually correct as a structural correlate of oligomerization; however it is not the informative core molecular function (which is the catalytic dUTP diphosphatase activity). Kept as non-core. Supporting Evidence: PMID:8805593 each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll beta barrel |
| GO:0042975 peroxisome proliferator activated receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-Compara electronic transfer of PPAR binding, corresponding to the reported "By similarity" moonlighting interaction in which dUTPase binds PPAR via its N-terminus. Reason: Peripheral moonlighting interaction inferred by similarity/ortholog projection, not the core function of DUT and without direct human experimental support in the cited evidence. Marked over-annotated rather than removed. Supporting Evidence: file:human/DUT/DUT-uniprot.txt Inhibits peroxisome proliferator- |
| GO:0043254 regulation of protein-containing complex assembly | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-Compara electronic transfer of "regulation of protein-containing complex assembly", plausibly relating to the reported inhibition of PPAR:RXR dimerization by dUTPase. Reason: This is an indirect, ortholog-projected process linked to the peripheral PPAR moonlighting activity, not the core nucleotide-metabolism function of DUT. Marked over-annotated rather than removed. Supporting Evidence: file:human/DUT/DUT-uniprot.txt preventing the latter's dimerization with retinoid X receptor |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence localization to the nucleoplasm, consistent with the nuclear isoform (DUT-N). Reason: Nucleoplasmic localization is consistent with the experimentally established nuclear localization of the DUT-N isoform and with Reactome's placement of the major isoform in the nucleoplasm. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0004170 dUTP diphosphatase activity | EXP PMID:17880943 Active site closure facilitates juxtaposition of reactant at... | ACCEPT | Summary: Direct experimental (structural/mechanistic) demonstration of dUTPase catalysis via the crystal structure of the enzyme:substrate-analog:Mg complex. Reason: Core, directly demonstrated molecular function of DUT, established by structural and equilibrium-binding characterization of the catalytic mechanism. Supporting Evidence: PMID:17880943 We determined the crystal structure of the enzyme:alpha,beta-imino-dUTP:Mg complex and performed equilibrium binding experiments in solution. |
| GO:0004170 dUTP diphosphatase activity | EXP PMID:8805593 Human dUTP pyrophosphatase: uracil recognition by a beta hai... | ACCEPT | Summary: Direct experimental demonstration of dUTP diphosphatase activity via the first atomic-resolution structure of human dUTPase in complex with uracil-containing deoxyribonucleotides. Reason: Core, directly demonstrated molecular function; the structure captures the enzyme bound to dUMP/dUDP/dUTP and defines the catalytic active site. Supporting Evidence: PMID:8805593 dUTPase hydrolyzes dUTP to dUMP and pyrophosphate |
| GO:0005634 nucleus | EXP PMID:9070952 Assignment of the human dUTPase gene (DUT) to chromosome 15q... | ACCEPT | Summary: Experimental subcellular localization to the nucleus (nuclear isoform), cited by UniProt for the DUT-N isoform. Reason: Nuclear localization of the nuclear dUTPase isoform is experimentally established; accept and defer to the curator who assessed the full text. The cached record is abstract-only, but UniProt cites this reference for the isoform-2 nuclear location. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0005739 mitochondrion | EXP PMID:9070952 Assignment of the human dUTPase gene (DUT) to chromosome 15q... | ACCEPT | Summary: Experimental subcellular localization to the mitochondrion (mitochondrial isoform DUT-M), cited by UniProt for isoform 3. Reason: Mitochondrial localization of the DUT-M isoform is experimentally established; accept and defer to the curator. Independently supported by high-confidence mitochondrial proteomics. Supporting Evidence: PMID:8631816 the higher molecular weight species (DUT-M) fractionates with the mitochondria |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput identification in a quantitative high-confidence human mitochondrial proteome (MitoCoP), consistent with the mitochondrial DUT-M isoform. Reason: Corroborates the experimentally established mitochondrial localization of the DUT-M isoform via a high-confidence mitochondrial proteomics resource. Supporting Evidence: PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP) |
| GO:0004170 dUTP diphosphatase activity | IDA PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: Direct assay of dUTP diphosphatase activity on purified human dUTPase (both nuclear and mitochondrial forms show identical dUTP binding). Reason: Core, directly demonstrated molecular function. dUTPase was purified from HeLa cells and both isoforms exhibited identical dUTP binding (KM ~2.5 uM). Supporting Evidence: PMID:8631816 both forms of dUTPase exhibited identical binding characteristics for dUTP |
| GO:0005634 nucleus | IDA PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: Direct demonstration (cellular fractionation / isopycnic density centrifugation) that the nuclear dUTPase isoform (DUT-N) localizes to the nucleus. Reason: Directly demonstrated nuclear localization of the DUT-N isoform. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0006231 dTMP biosynthetic process | IDA PMID:10952785 Deoxyuridine triphosphatase (dUTPase) expression and sensiti... | ACCEPT | Summary: dUTPase supplies dUMP and maintains low dUTP, acting upstream of thymidylate synthase in de novo dTMP biosynthesis; dUTPase expression/activity modulates the dUTP pool and sensitivity to thymidylate synthase inhibition. Reason: dUTPase is functionally upstream of dTMP biosynthesis: it produces the TYMS substrate dUMP and limits uracil misincorporation when dTTP is depleted. The acts_upstream_of_or_within qualifier is appropriate. Supporting Evidence: PMID:10952785 dUTPase catalyses the hydrolysis of dUTP to dUMP, thereby maintaining low intracellular dUTP. |
| GO:0006231 dTMP biosynthetic process | IMP PMID:15322254 Small interfering RNA-mediated suppression of dUTPase sensit... | ACCEPT | Summary: siRNA knockdown of dUTPase perturbs the dUTP pool and sensitizes cancer cells to the thymidylate synthase inhibitor FUdR, functionally linking dUTPase to dTMP biosynthesis / thymineless pathways. Reason: Loss-of-function (siRNA) evidence places dUTPase upstream of dTMP biosynthesis and the thymidylate-synthase pathway; acts_upstream_of_or_within is appropriate. Supporting Evidence: PMID:15322254 Suppression of dUTPase in SW620 and MCF-7 cells resulted in a significant enhancement in dUTP pool expansion after TS inhibition. |
| GO:0005634 nucleus | IDA PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: The nuclear dUTPase isoform (DUT-N) is active in the nucleus, where it depletes dUTP to protect replicating DNA from uracil misincorporation. Reason: is_active_in nucleus is appropriate: the catalytically active DUT-N isoform is localized to the nucleus, the compartment where prevention of uracil misincorporation into replicating DNA is most relevant. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0006231 dTMP biosynthetic process | IDA PMID:10952785 Deoxyuridine triphosphatase (dUTPase) expression and sensiti... | ACCEPT | Summary: dUTPase is involved in de novo dTMP biosynthesis by producing dUMP and keeping dUTP low; dUTPase activity modulates sensitivity to thymidylate synthase inhibition. Reason: Involvement in dTMP biosynthesis is well supported: dUTPase furnishes the dUMP substrate for thymidylate synthase and its activity governs the dUTP:dTTP balance. Supporting Evidence: PMID:10952785 dUTPase catalyses the hydrolysis of dUTP to dUMP, thereby maintaining low intracellular dUTP. |
| GO:0006231 dTMP biosynthetic process | IDA PMID:15322254 Small interfering RNA-mediated suppression of dUTPase sensit... | ACCEPT | Summary: dUTPase involvement in dTMP biosynthesis / thymidylate metabolism, supported by the effect of dUTPase suppression on dUTP pools and thymidylate-synthase-inhibitor sensitivity. Reason: Involved_in dTMP biosynthetic process is supported by loss-of-function evidence linking dUTPase to the dUTP/dTTP balance and thymidylate synthesis pathway. Supporting Evidence: PMID:15322254 dUTPase, which eliminates dUTP from the DNA biosynthetic pathway, opposes uracil misincorporation |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: Detected as an mRNA-binding protein in a HeLa "interactome capture" (UV crosslinking) proteomic screen. This is a high-throughput moonlighting/incidental RNA-association finding, not a characterized function of dUTPase. Reason: RNA binding was reported only from a global mRNA-interactome capture screen; there is no evidence that RNA binding is a core or physiologically important function of dUTPase (a nucleotide-hydrolase). Treated as non-core moonlighting and marked over-annotated. Retained (not removed) as a high-throughput experimental result. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: Detected by mass spectrometry in the proteome of B-cell-derived exosomes. This is a high-throughput proteomic survey; dUTPase is an intracellular nucleotide- metabolism enzyme and is not a functional exosomal component. Reason: Extracellular exosome detection reflects incidental presence in a bulk exosome proteome, not a functionally meaningful localization for a nuclear/mitochondrial housekeeping enzyme. Marked over-annotated rather than removed. Supporting Evidence: PMID:20458337 we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-73666 | ACCEPT | Summary: Reactome places the major (nuclear) dUTPase isoform in the nucleoplasm, where it catalyzes hydrolysis of dUTP to dUMP and pyrophosphate. Reason: Consistent with the experimentally established nuclear localization of the DUT-N isoform and with the HPA nucleoplasm IDA annotation. Supporting Evidence: Reactome:R-HSA-73666 The major one, annotated here, is localized to the nucleoplasm |
| GO:0004170 dUTP diphosphatase activity | TAS PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: Traceable author statement of dUTP diphosphatase activity for human dUTPase. Reason: Redundant with the direct experimental annotations for the same term; correct core molecular function. Supporting Evidence: PMID:8631816 both forms of dUTPase exhibited identical binding characteristics for dUTP |
| GO:0005634 nucleus | TAS PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: Traceable author statement of nuclear localization for the DUT-N isoform. Reason: Redundant with the IDA/EXP nucleus annotations; correct localization of the nuclear isoform. Supporting Evidence: PMID:8631816 the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus |
| GO:0005739 mitochondrion | TAS PMID:8631816 Characterization of distinct nuclear and mitochondrial forms... | ACCEPT | Summary: Traceable author statement of mitochondrial localization for the DUT-M isoform. Reason: Redundant with the EXP/HTP mitochondrion annotations; correct localization of the mitochondrial isoform. Supporting Evidence: PMID:8631816 the higher molecular weight species (DUT-M) fractionates with the mitochondria |
| GO:0006139 nucleobase-containing compound metabolic process | TAS PMID:1325640 Human dUTP pyrophosphatase: cDNA sequence and potential biol... | MARK AS OVER ANNOTATED | Summary: Traceable author statement placing dUTPase in nucleotide/nucleobase-containing compound metabolism. This is a very broad parent process. Reason: Correct but extremely general; the specific dUTP catabolic / dUMP biosynthetic / dTMP biosynthetic process annotations already capture DUT's role at the appropriate level of granularity. Marked over-annotated as a too-broad term. Supporting Evidence: PMID:1325640 dUTPase may generally perform an essential role in DNA replication |
| GO:0006260 DNA replication | TAS PMID:1325640 Human dUTP pyrophosphatase: cDNA sequence and potential biol... | MARK AS OVER ANNOTATED | Summary: Traceable author statement associating dUTPase with DNA replication. dUTPase supports faithful replication by keeping dUTP low (preventing uracil misincorporation) and supplying dUMP for dTTP, but it is not part of the replication machinery itself. Reason: dUTPase influences the fidelity of DNA replication indirectly, by controlling the deoxyribonucleotide pool, rather than acting in the DNA replication process per se. "DNA replication" (involved_in) over-states its direct role; the causal contribution is better captured by its nucleotide-metabolism annotations. Marked over-annotated rather than removed (traceable author statement). Supporting Evidence: PMID:1325640 dUTPase may generally perform an essential role in DNA replication |
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Download this section (compressed HTML)Q: Do the nuclear (DUT-N) and mitochondrial (DUT-M) isoforms have non-redundant physiological roles, or does one compartment's activity suffice for genome integrity under normal conditions?
Q: Is the reported PPAR-inhibition / signaling-receptor-inhibitor moonlighting function present and physiologically relevant in humans, or is it specific to the rodent ortholog from which it was projected?
Experiment: Isoform-specific rescue of DUT-null cells with nuclear-only vs mitochondrial-only dUTPase to test compartmental requirements for preventing uracil misincorporation.
Experiment: Quantify dUTP:dTTP pools and uracil-DNA content in cells carrying the BMFDMS variants (Y142C, R173W, Y227C) to link catalytic impairment to the disease phenotype.
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