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0.039
ATP
isoform NMNAT3, in 30 mM HEPES/KOH, pH 7.5, at 37°C
0.1176
nicotinamide ribonucleotide
isoform NMNAT3, in 30 mM HEPES/KOH, pH 7.5, at 37°C
0.00295 - 0.0385
nicotinamide ribonucleotide
0.0335
ATP
isoform NMNAT1, in 30 mM HEPES/KOH, pH 7.5, at 37°C
0.082
ATP
isoform NMNAT2, in 30 mM HEPES/KOH, pH 7.5, at 37°C
0.08425
ATP
-
wild type enzyme, in 50 mM HEPES-NaOH, pH 7.5, temperature not specified in the publication
0.113
ATP
-
mutant enzyme C164S/C165S, in 50 mM HEPES-NaOH, pH 7.5, temperature not specified in the publication
0.00295
nicotinamide ribonucleotide
-
mutant enzyme C164S/C165S, in 50 mM HEPES-NaOH, pH 7.5, temperature not specified in the publication
0.00691
nicotinamide ribonucleotide
-
wild type enzyme, in 50 mM HEPES-NaOH, pH 7.5, temperature not specified in the publication
0.0252
nicotinamide ribonucleotide
isoform NMNAT1, in 30 mM HEPES/KOH, pH 7.5, at 37°C
0.0385
nicotinamide ribonucleotide
isoform NMNAT2, in 30 mM HEPES/KOH, pH 7.5, at 37°C
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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+
malfunction
-
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
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
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
physiological function
NMNAT1 is an enzyme in the NAD biosynthetic pathway that generates NAD in the nucleus
physiological function
-
nicotinamide mononucleotide adenylyltransferase 2 regulates axon integrity in the mouse embryo
physiological function
-
overexpression of isoform Nmnat2 is toxic to primary neurons resulting in pervasive cell death
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
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
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E198P/L217R
mutation disrupts the dimer interface, leading to a mixture of dimer and monomer in solution
C164S/C165S
-
the mutant protein is not palmitoylated (soluble), appears diffuse in the cytoplasm and does not colocalize with GM130. However, the mutant is fully active and shows even higher kcat values compared to the wild type enzyme
WldS(W258A)
the chimeric WldS protein is composed of the N-terminal 70 aa of Ufd2a/Ube4b, an ubiquitin-chain assembly factor, fused to the complete sequence of NMNAT1, the W258A mutation disrupts the NAD-synthesizing activity
additional information
naturally occuring mutant mice, wldS, showing delayed Wallerian degeneration phenotype, suggest that axonal degeneration is an active process, the wldS mutation comprises an 85 kb tandem triplicon, which causes overexpression of the chimeric WldS protein composed of the N-terminal 70 aa of Ufd2a/Ube4b, an ubiquitin-chain assembly factor, fused to the complete sequence of NMNAT1
additional information
naturally occuring mutant mice, wldS, showing delayed Wallerian degeneration phenotype, suggest that axonal degeneration is an active process, the wldS mutation comprises an 85 kb tandem triplicon, which causes overexpression of the chimeric WldS protein composed of the N-terminal 70 aa of Ufd2a/Ube4b, an ubiquitin-chain assembly factor, fused to the complete sequence of NMNAT1
additional information
-
naturally occuring mutant mice, wldS, showing delayed Wallerian degeneration phenotype, suggest that axonal degeneration is an active process, the wldS mutation comprises an 85 kb tandem triplicon, which causes overexpression of the chimeric WldS protein composed of the N-terminal 70 aa of Ufd2a/Ube4b, an ubiquitin-chain assembly factor, fused to the complete sequence of NMNAT1
additional information
NMNAT1 overexpression reduces brain infarction size and improves behavioral outcomes in mice with ischemic stroke
additional information
-
NMNAT1 overexpression reduces brain infarction size and improves behavioral outcomes in mice with ischemic stroke
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Boulton, S.; Kyle, S.; Durkacz, B.W.
Low nicotinamide mononucleotide adenylyltransferase activity in a tiazofurin-resistant cell line: effects on NAD metabolism and DNA repair
Br. J. Cancer
76
845-851
1997
Mus musculus, Mus musculus L1210
brenda
Yalowitz, J.A.; Jayaram, H.N.
Modulation of cytotoxicity of benzamide riboside by expression of NMN adenylyltransferase
Curr. Med. Chem.
9
749-758
2002
Saccharomyces cerevisiae, Homo sapiens, Mammalia, Mus musculus
brenda
Conforti, L.; Fang, G.; Beirowski, B.; Wang, M.S.; Sorci, L.; Asress, S.; Adalbert, R.; Silva, A.; Bridge, K.; Huang, X.P.; Magni, G.; Glass, J.D.; Coleman, M.P.
NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration
Cell Death Differ.
14
116-127
2007
Mus musculus
brenda
Sasaki, Y.; Araki, T.; Milbrandt, J.
Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy
J. Neurosci.
26
8484-8491
2006
Mus musculus (Q99JR6), Mus musculus (Q9EPA7)
brenda
Watanabe, M.; Tsukiyama, T.; Hatakeyama, S.
Protection of vincristine-induced neuropathy by WldS expression and the independence of the activity of Nmnat1
Neurosci. Lett.
411
228-232
2007
Mus musculus
brenda
Jia, H.; Yan, T.; Feng, Y.; Zeng, C.; Shi, X.; Zhai, Q.
Identification of a critical site in Wld(s): essential for Nmnat enzyme activity and axon-protective function
Neurosci. Lett.
413
46-51
2007
Mus musculus
brenda
Yahata, N.; Yuasa, S.; Araki, T.
Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration
J. Neurosci.
29
6276-6284
2009
Mus musculus (Q99JR6), Mus musculus (Q9EPA7), Mus musculus
brenda
Mayer, P.R.; Huang, N.; Dewey, C.M.; Dries, D.R.; Zhang, H.; Yu, G.
Expression, localization, and biochemical characterization of nicotinamide mononucleotide adenylyltransferase 2
J. Biol. Chem.
285
40387-40396
2010
Mus musculus, Homo sapiens (Q9BZQ4)
brenda
Raches, D.W.; Xiao, S.; Kusumanchi, P.; Yalowitz, J.; Sanghani, P.; Long, E.C.; Antony, A.C.; Jayaram, H.N.
Cloning, expression and characterization of mouse (Mus musculus) nicotinamide 5-mononucleotide adenylyltransferase-2
Med. Chem.
7
718-726
2011
Mus musculus
brenda
Hicks, A.N.; Lorenzetti, D.; Gilley, J.; Lu, B.; Andersson, K.E.; Miligan, C.; Overbeek, P.A.; Oppenheim, R.; Bishop, C.E.
Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) regulates axon integrity in the mouse embryo
PLoS ONE
7
e47869
2012
Mus musculus
brenda
Orsomando, G.; Cialabrini, L.; Amici, A.; Mazzola, F.; Ruggieri, S.; Conforti, L.; Janeckova, L.; Coleman, M.P.; Magni, G.
Simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues
PLoS ONE
7
e53271
2012
Mus musculus (Q5HZI3), Mus musculus (Q99JR6), Mus musculus (Q9EPA7), Mus musculus
brenda
Mao, X.R.; Kaufman, D.M.; Crowder, C.M.
Nicotinamide mononucleotide adenylyltransferase promotes hypoxic survival by activating the mitochondrial unfolded protein response
Cell Death Dis.
7
e2113
2016
Mus musculus (Q9EPA7), Mus musculus
brenda
Liang, J.; Wang, P.; Wei, J.; Bao, C.; Han, D.
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
Neurochem. Res.
40
1102-1110
2015
Mus musculus (Q9EPA7), Mus musculus
brenda
Rossi, F.; Geiszler, P.C.; Meng, W.; Barron, M.R.; Prior, M.; Herd-Smith, A.; Loreto, A.; Lopez, M.Y.; Faas, H.; Pardon, M.C.; Conforti, L.
NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau mouse model of tauopathy
Behav. Brain Res.
339
140-152
2018
Mus musculus (Q9EPA7), Mus musculus
brenda
Ma, X.; Zhu, Y.; Lu, J.; Xie, J.; Li, C.; Shin, W.; Qiang, J.; Liu, J.; Dou, S.; Xiao, Y.; Wang, C.; Jia, C.; Long, H.; Yang, J.; Fang, Y.; Jiang, L.; Zhang, Y.; Zhang, S.; Zhai, R.; Liu, C.; Li, D.
Nicotinamide mononucleotide adenylyl transferase uses its NAD+ substrate-binding site to chaperone phosphorylated TAU
eLife
9
e51859
2020
Mus musculus (Q99JR6), Drosophila melanogaster (Q9VC03)
brenda
Yue, Z.; Ma, Y.; You, J.; Li, Z.; Ding, Y.; He, P.; Lu, X.; Jiang, J.; Chen, S.; Liu, P.
NMNAT3 is involved in the protective effect of SIRT3 in Ang II-induced cardiac hypertrophy
Exp. Cell Res.
347
261-273
2016
Mus musculus (Q99JR6)
brenda
Pottorf, T.; Mann, A.; Fross, S.; Mansel, C.; Vohra, B.P.S.
Nicotinamide mononucleotide adenylyltransferase 2 maintains neuronal structural integrity through the maintenance of golgi structure
Neurochem. Int.
121
86-97
2018
Mus musculus (Q8BNJ3)
brenda