Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Combined Automated Annotation using Multiple IEA Methods
Cloning, characterisation and crystallisation of a diadenosine 5',5"'-P(1),P(4)-tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans.
The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms.
Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate.
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Human Ap4A hydrolase hydrolyses PRPP only weakly in vitro (kcat 0.057 s-1).
"the human diadenosine tetraphosphate hydrolase, and human DIPP-1"
Structure and substrate-binding mechanism of human Ap4A hydrolase.
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NMR structures of human NUDT2 free and ATP-bound; asymmetric cleavage of Ap4A to ATP + AMP.
"The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP."
Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells.
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NUDT2 degrades Ap4A after mast-cell activation; knockdown changes MITF and USF2 target-gene expression.
"The knockdown of Ap(4)A hydrolase modulated Ap(4)A accumulation, resulting in changes in the expression of MITF and USF2 target genes."
Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation.
Crystal structure of wild-type and mutant human Ap4A hydrolase.
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Crystal structures of wild-type and E58A human NUDT2 show a monomeric Nudix alpha-beta-alpha sandwich; the enzyme cleaves at the fourth phosphate from the bound adenosine.
"Similar to the canonical Nudix fold, the human Ap4A hydrolase monomer shows the common αβα-sandwich architecture."
OpenScientist deep research for NUDT2
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Deep research frames NUDT2 as a dual-function Ap4A hydrolase and mRNA decapping enzyme, and notes that direct human localisation data are sparse.
"Direct human (vs. ortholog) localization data are sparse."
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Extracellular Ap4A hydrolysis is performed by ecto-PDE/ENPP enzymes, not NUDT2.
"underscoring that NUDT2's functional niche is strictly intracellular"
A proteome-scale map of the human interactome network.
NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.
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NUDT2 disruption in KBM-7 cells raises Ap4A 175-fold and alters thousands of transcripts, notably down-regulating interferon and inflammation pathways.
"causing a 175-fold increase in intracellular Ap4A"
Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization.
A reference map of the human binary protein interactome.
Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.
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Nudt2 removes FAD and dpCoA caps from RNA in vitro but not NAD caps; no change in cellular FAD-capped RNA in Nudt2-KO cells.
"Whereas Nudt2 possesses deFADding activity on FAD-capped RNAs in vitro (Figure 4), it does not hydrolyze NAD-capped RNA (Figure 1)."
Novel NUDT2 variant causes intellectual disability and polyneuropathy.
NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.
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NUDT2 sequentially dephosphorylates 5'-PPP RNA to P-RNA for XRN1 decay; NUDT2 loss increases growth of PPP-RNA viruses in cells; NUDT2 is nuclear and cytoplasmic.
"NUDT2 sequentially releases two phosphates, and a monophosphorylated RNA is generated that can then serve as a substrate for the cellular exonuclease XRN1."
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Nudt2 knockout mice are viable with no overt phenotype and no survival difference after VSV infection.
"Homozygous knockout mice were viable, bred with expected Mendelian ratios"
Diadenosine Tetraphosphate (Ap(4) A) Serves as a 5' RNA Cap in Mammalian Cells.
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NUDT2 and DXO cleave Ap4A-capped RNA.
"A decapping enzyme screen identifies two enzymes cleaving Ap4 A-RNA,NUDT2 and DXO"
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.
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Biallelic NUDT2 variants (18 patients, 10 families) abolish enzymatic activity; decapping loss underlies altered mRNA homeostasis.
"We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder."
The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants.
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Compound heterozygous NUDT2 variants (p.R12*, p.I65R) cause ID.
"Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID)."
Human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase is a member of the MutT family of nucleotide pyrophosphatases.
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Cloning of human NUDT2 cDNA; Nudix (MutT) motif; unrelated to prokaryotic (symmetrical) Ap4A hydrolases.
"It is unrelated to the enzymes of diadenosine tetraphosphate catabolism found in prokaryotes and fungi."
Detoxification of Reactive Oxygen Species
NUDT2 hydrolyses GP4G to GTP, GMP