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.
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The C. elegans orthologue ndx-4 is an asymmetrical Ap4A hydrolase producing AMP + ATP (Km 7 uM, kcat 27 s-1), behaving as a typical animal Ap4A hydrolase.
"It hydrolyses Ap4A with a K(m) of 7 microM and k(cat) of 27 s(-1) producing AMP and ATP as products."
The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms.
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Structures of the worm orthologue show a Nudix fold and explain specificity for dinucleoside tetraphosphates over triphosphates; apoptosis is mentioned only as a speculative consequence of Ap4A regulation.
"These results suggest how the enzyme can catalyze the hydrolysis of a range of related dinucleoside tetraphosphate, but not triphosphate, compounds through precise orientation of key elements of the substrate."
A mitochondrial protein compendium elucidates complex I disease biology.
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Large-scale mouse mitochondrial proteomics (MitoCarta); source of the HDA mitochondrion annotation. Nudt2 is not discussed in the text.
"we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes and their protein expression across 14 mouse tissues."
Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells.
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The Nudt2 gene product is responsible for Ap4A degradation after immunological activation of mast cells; its knockdown alters Ap4A accumulation and expression of MITF and USF2 target genes.
"The knockdown of Ap(4)A hydrolase modulated Ap(4)A accumulation, resulting in changes in the expression of MITF and USF2 target genes."
Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.
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Recombinant mouse Nudt2 has dpCoA-cap and FAD-cap RNA decapping activity in vitro, lost in the EE-QQ catalytic mutant, and no deNADding activity.
"Additionally, we identify seven Nudix proteins (Nudt2, Nudt7, Nudt8, Nudt15, Nudt16 and Nudt19) that possess dpCoA cap decapping (deCoAping) activity in vitro, and two Nudix proteins (Nudt2 and Nudt16) possessing FAD cap decapping (deFADding) activity."
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Loss of Nudt2 in cells did not change FAD-capped RNA levels, so a cellular deFADding role is not supported.
"while a similar function cannot be attributed to Nudt2 at least under the growth conditions and the cells employed"
Multiple Nudix family proteins possess mRNA decapping activity.
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Recombinant mouse Nudt2 decaps monomethylated and unmethylated capped RNA in vitro, releasing both m7GMP and m7GDP.
"Here we demonstrate that six additional mouse Nudix proteins--Nudt2, Nudt3, Nudt12, Nudt15, Nudt17, and Nudt19--have varying degrees of decapping activity in vitro on both monomethylated and unmethylated capped RNAs."
NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.
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Disruption of human NUDT2 in KBM-7 cells raises intracellular Ap4A 175-fold and alters expression of thousands of genes.
"KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A"
NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.
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Recombinant NUDT2 dephosphorylates 5'-triphosphorylated RNA in two sequential steps to a 5'-monophosphorylated RNA that XRN1 can degrade; the E58A Nudix-box mutant is inactive.
"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 and breed at Mendelian ratios.
"Homozygous knockout mice were viable, bred with expected Mendelian ratios"
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Bone-marrow-derived cells from Nudt2-knockout mice support 10- to 30-fold more growth of viruses generating 5'-PPP RNA than littermate controls, with no effect on other viruses.
"We concluded from these studies that mouse NUDT2 impairs the growth of PPP-RNA generating viruses in vitro, but it does not affect the accumulation of other viruses."
Diadenosine Tetraphosphate (Ap(4) A) Serves as a 5' RNA Cap in Mammalian Cells.
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Ap4A-capped RNA exists in human and rat cells and NUDT2 is one of two enzymes that cleave it.
"A decapping enzyme screen identifies two enzymes cleaving Ap4 A-RNA,NUDT2 and DXO, both of which also cleave other substrate RNAs in vitro."
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.
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Biallelic loss-of-function NUDT2 variants cause a recessive neurodevelopmental disorder; add-back experiments implicate loss of decapping in the altered mRNA homeostasis of patient fibroblasts.
"Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis."
OpenScientist deep research for Nudt2