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malfunction
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absisic acid-induced oxidative stress causes stomatal cell death in a nicotinamide mononucleotide adenyltransferase mutant. Stomata partially lose their ability to close leading to drought susceptibility and the stomata are less responsive to opening cues
malfunction
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enzyme loss results in ubiquitination, mislocalization and aggregation of the Bruchpilot protein, and subsequent active zone degeneration
malfunction
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nicotinamide mononucleotide adenylyltransferase 2 (Nmat2) homozygous deletion mutants show an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion. In the absence of Nmnat2, major target organs and tissues (e.g., muscle) are not functionally innervated resulting in perinatal lethality
malfunction
colorectal cancer cells, that exhibit low levels of NMNAT2 and are refractory to tiazofurin, can be rendered sensitive to Tiazofurin by overexpressing NMNAT2
malfunction
deletion of POF1 significantly lowers NAD+ levels and decreases the efficiency of nicotinamide riboside utilization, resistance to oxidative stress, and nicotinamide riboside-induced life span extension
malfunction
gain-of-function mutations in the mouse nicotinamide mononucleotide adenylyltransferase type 1, Nmnat1, produce two remarkable phenotypes: protection against traumatic axonal degeneration and reduced hypoxic brain injury, the mechanism involves the mitochondrial unfolded protein response (mitoUPR) factor, penotype, overview
malfunction
knockdown of NMNAT-2 significantly reduces cellular NAD+ levels and protects cells from p53-dependent cell death upon DNA damage. p53 knockdown abolishes NMNAT-2 expression upon actinomycin D treatment. In NMNAT-2-knockdown cells, actinomycin D treatment does not result in enhanced immunoreactivity
malfunction
NMNAT1 overexpression reduces cell death and apoptosis both in vitro and in vivo. NMNAT1 knockdown exacerbates cell death and apoptosis. NMNAT1 overexpression regulates neuron survival via AMPK activation, as NMNAT1 overexpression enhances AMPKactivity in OGD-treated cortical neurons, and AMPK inhibitor blocks LV-NMNAT1-induced neuroprotection in OGD-treated cortical neurons
malfunction
the chromosomal region encoding the nuclear NAD+ synthesis enzyme NMNAT1 is frequently deleted in human cancer, which may contribute to tumor development. Knockdown of NMNAT1 enhances rRNA transcription and promotes cell death after nutrient deprivation. Heterozygous deletion of NMNAT1 in lung tumor cell lines correlates with low expression level and increased sensitivity to DNA damage. NMNAT1 knockdown stimulates p53 acetylation level before and after DNA damage with doxorubicin
malfunction
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deletion of POF1 significantly lowers NAD+ levels and decreases the efficiency of nicotinamide riboside utilization, resistance to oxidative stress, and nicotinamide riboside-induced life span extension
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metabolism
gene expression of NAD+ synthesizing enzymes in the NAD+ salvage pathways can be modulated by p53
metabolism
NAD+ biosynthesis is performed by de novo and salvage pathways, which converge on the step that is catalysed by the enzyme nicotinamide mononucleotide adenylyltransferase, NMNAT
metabolism
nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the biosynthesis of NAD+ and NaAD+
metabolism
NMNAT1 catalyzes NAD+ synthesis in the last step of a salvage synthesis pathway that recycles nicotinamide (NAM) back to NAD+. NMNAT1 deletion in tumors may contribute to transformation by increasing rRNA synthesis, but may also increase sensitivity to nutrient stress and DNA damage
metabolism
the enzyme is essentially involved in the NAD biosynthesis via two different pathways, overview
metabolism
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NAD+ biosynthesis is performed by de novo and salvage pathways, which converge on the step that is catalysed by the enzyme nicotinamide mononucleotide adenylyltransferase, NMNAT
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metabolism
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nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the biosynthesis of NAD+ and NaAD+
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physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
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NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
NMNAT1 is an enzyme in the NAD biosynthetic pathway that generates NAD in the nucleus
physiological function
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nicotinamide mononucleotide adenylyltransferase (NMAT)is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1alpha pathway. NMAT is a stress response protein required for thermotolerance and mitigation of oxidative stress-induced shortened lifespan
physiological function
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nicotinamide mononucleotide adenylyltransferase 2 regulates axon integrity in the mouse embryo
physiological function
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overexpression of isoform Nmnat2 is toxic to primary neurons resulting in pervasive cell death
physiological function
overexpression of isoform Nmnat2 is toxic to primary neurons resulting in pervasive cell death
physiological function
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the enzyme has both NAD synthase and chaperone function. The enzyme is essential for maintaining neuronal integrity under normal conditions and protects against several neurodegenerative conditions. Enzyme overexpression significantly suppresses both behavioral and morphological deficits associated with tauopathy by means of reducing the levels of hyperphosphorylated tau oligomers and rescueing age-dependent vacuolization induced by tau expression. The enzyme interacts with phosphorylated tau in vivo and promotes the ubiquitination and clearance of toxic tau species. Apoptosis activation is significantly reduced in brains overexpressing the enzyme, and neurodegeneration is suppressed
physiological function
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the enzyme is essential for the maintenance of NAD homeostasis enabling sustainable stomatal movement. The enzyme is responsible for tolerance to stressful signalling in guard cells during stomatal closure
physiological function
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the enzyme is required for maintaining active zone structural integrity in Drosophila by interacting with the active zone protein Bruchpilot and shielding it from activity-induced ubiquitin-proteasome-mediated degradation. The enzyme specifically maintains active zone structure by direct protein-protein interaction
physiological function
the enzyme plays a key role in NAD+ biosynthesis
physiological function
isozyme nicotinamide mononucleotide adenylyltransferase 1 protects neural cells against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke through AMP-activated protein kinase activation. NMNAT1 overexpression reduces brain infarction size and improves behavioral outcomes in mice with ischemic stroke. Role and mechanism of NMNAT1 in the regulation of neural ischemic injuries by using cultured cortical neurons with oxygen-glucose deprivation of ischemic injury in vitro and mouse transient middle cerebral artery occlusion (MCAO) model of stroke in vivo, overview
physiological function
nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription and plays a role in preventing cell death after damage. It interacts with the nucleolar repressor protein nucleomethylin. Isozyme NMNAT1 participates in the regulation of rRNA biosynthesis, possibly by producing a local supply of NAD+. And NMNAT1 may be regulated by recruitment into complexes that consume NAD+. The enzyme is recruited into a ternary complex containing the NAD+-dependent deacetylase SirT1. NMNAT1 expression stimulates the deacetylase function of SirT1 to deacetylate p53. Nucleolar protein nucleomethylin, NML, promotes interaction between SirT1 and NMNAT1, and NMNAT1 is recruited to the nucleolar transcriptional repressor complex eNoSC by NML
physiological function
nicotinamide mononucleotide adenylyltransferase catalyzes the central step in nicotinamide adenine dinucleotide (NAD+) biosynthesis, making it essential for survival
physiological function
the enzyme is a target for the tumor suppressor p53, a major player in cancer signaling pathways, that is an important regulator of cellular metabolism. Determination of an important functional role of NMNAT-2 in p53-mediated signaling. Enzyme NMNAT-2 plays an important role in p53-mediated cell death upon DNA damage
physiological function
tiazofurin is a pro-drug that is metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2 (NMNAT2) to thiazole-4-carboxamide adenine dinucleotide, a potent inhibitor of inosine 5'-monophosphate dehydrogenase required for cellular guanylate synthesis. Resistance of colorectal cancer cell-kill to Tiazofurin can be overcome by sequentially overexpressing hNMNAT2 and then facilitating the uptake of Tiazofurin by folate-tethered nanoparticles, which enter cells via folate receptors
physiological function
the enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) acts not only as a NAD synthase involved in axonal maintenance but as a molecular chaperone helping neurons to overcome protein unfolding and protein aggregation, molecular mechanism, overview. NMNAT2 acts as a molecular chaperone that cooperates with HSP90 to refold denatured proteins (foldase activity) and independently prevents protein unfolding (holdase activity). In vertebrates, the isoform NMNAT2, highly expressed in the brain, functions as a cytosolic protein bound to Golgi-derived vesicles through the palmitoylation of several cysteine residues. NMNAT2 seems to be essential for axonal growth or maintenance during embryogenesis. Enzyme NMNAT2 complexes with heat shock protein 90 (HSP90), an abundant and ubiquitous molecular chaperone that plays an essential role in maintaining protein homeostasis
physiological function
the enzyme is involved in the salvage pathways for NAD+ biosynthesis
physiological function
crossing of htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer's disease, with Nmnat1 transgenic and knockout mice. In the resulting offspring until the age of 6 months, overexpression of NMNAT1 ameliorates the early deficit in food burrowing characteristic of htau mice. At 6 months of age, htau mice do not show neurodegenerative changes in both the cortex and hippocampus, and these are not induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produces a corresponding effect on NMNAT enzymatic activity but does not alter NAD levels in htau mice
physiological function
Golgi fragmentation in cultured dorsal root ganglion neurons results in caspase dependent axon degeneration and neuronal cell death. NMNAT2 depletion in these neurons causes Golgi fragmentation and caspase dependent axon degeneration. NMNAT2 depletion does not cause ATP loss in the axons. Cytosolic Nmnat1 overexpression inhibits the axon degeneration induced by Golgi fragmentation or NMNAT2 depletion
physiological function
NMNAT overexpression strains show increased colony growth on different carbon sources, and intracellular Ca2+ concentrations are increased by 2- to 2.30fold, respectively, compared with wild-type. In the overexpressing strains, endo-beta-glucanase activity and beta-glucosidase activity are increased
physiological function
NMNAT serves as a chaperone of phosphorylated Tau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in Drosophila tauopathy models overexpressing human Tau. NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of Tau, which can be competitively disrupted by the enzymatic substrates of NMNAT. NMNAT serves as a cochaperone of Hsp90 for the specific recognition of phosphorylated Tau over Tau
physiological function
NMNAT shows strong interaction with phosphorylated truncated Tau protein. The binding affinity of NMNAT3 to phosphorylated Tau is about one order of magnitude higher than that to Tau.The phosphorylated Ser residues of Tau are the primary binding sites. Substrates (i.e. NMN and ATP) and the chaperone client phosphorylated Tau share the same binding pocket with a partial overlap at the phosphate-binding site
physiological function
NMNAT3 is a target and binding partner of sirtuin SIRT3. SIRT3 physically interacts with and deacetylates NMNAT3, thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects. NMNAT3 regulates the activity of SIRT3 via synthesis of mitochondrial NAD+
physiological function
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the enzyme plays a key role in NAD+ biosynthesis
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physiological function
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the enzyme is involved in the salvage pathways for NAD+ biosynthesis
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additional information
residues Arg11 and Arg136 are implicated in binding the phosphate groups of the ATP substrate. Residue Arg47 does not interact with either NMN or ATP substrates directly, but is deemed to play a role in binding as it is proximal to Arg11 and Arg136, plasticity of the active site
additional information
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residues Arg11 and Arg136 are implicated in binding the phosphate groups of the ATP substrate. Residue Arg47 does not interact with either NMN or ATP substrates directly, but is deemed to play a role in binding as it is proximal to Arg11 and Arg136, plasticity of the active site
additional information
structural homology modeling using human NMNAT3, PDB ID 1NUP, B chain, as a template, overview
additional information
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structural homology modeling using human NMNAT3, PDB ID 1NUP, B chain, as a template, overview
additional information
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residues Arg11 and Arg136 are implicated in binding the phosphate groups of the ATP substrate. Residue Arg47 does not interact with either NMN or ATP substrates directly, but is deemed to play a role in binding as it is proximal to Arg11 and Arg136, plasticity of the active site
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