Description: Homo sapiens nicotinamide nucleotide adenylyltransferase 3 (NMNAT3), transcript variant 1, mRNA. RefSeq Summary (NM_178177): This gene encodes a member of the nicotinamide/nicotinic acid mononucleotide adenylyltransferase family. These enzymes use ATP to catalyze the synthesis of nicotinamide adenine dinucleotide or nicotinic acid adenine dinucleotide from nicotinamide mononucleotide or nicotinic acid mononucleotide, respectively. The encoded protein is localized to mitochondria and may also play a neuroprotective role as a molecular chaperone. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]. Transcript (Including UTRs) Position: hg19 chr3:139,279,023-139,346,606 Size: 67,584 Total Exon Count: 4 Strand: - Coding Region Position: hg19 chr3:139,279,852-139,346,566 Size: 66,715 Coding Exon Count: 4
ID:NMNA3_HUMAN DESCRIPTION: RecName: Full=Nicotinamide mononucleotide adenylyltransferase 3; Short=NMN adenylyltransferase 3; AltName: Full=Nicotinate-nucleotide adenylyltransferase 3; Short=NaMN adenylyltransferase 3; EC=2.7.7.18; AltName: Full=Pyridine nucleotide adenylyltransferase 3; Short=PNAT-3; EC=2.7.7.1; FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following injury. CATALYTIC ACTIVITY: ATP + nicotinamide ribonucleotide = diphosphate + NAD(+). CATALYTIC ACTIVITY: ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD(+). COFACTOR: Divalent metal cations. Magnesium confers the highest activity. ENZYME REGULATION: Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')- tetraphosphate (Nap4AD). BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=209 uM for NMN; KM=130 uM for NAD(+); KM=29 uM for ATP; KM=390 uM for PPi; KM=276 uM for GTP; KM=350 uM for ITP; KM=111 uM for NaMN; KM=130 uM for NMNH; KM=2.01 uM for triazofurin monophosphate; Vmax=3.6 umol/min/mg enzyme for NAD synthesis; Vmax=12.8 umol/min/mg enzyme for pyrophosphorolytic NAD(+) cleavage; Vmax=2.9 umol/min/mg enzyme for pyrophosphorolytic NADH cleavage; PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1. SUBUNIT: Homotetramer. SUBCELLULAR LOCATION: Mitochondrion. TISSUE SPECIFICITY: Expressed in lung and spleen with lower levels in placenta and kidney. SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): NMNAT3 CDC HuGE Published Literature: NMNAT3 Positive Disease Associations: Brain
, Electrocardiography Related Studies:
Brain Sudha Seshadri et al. BMC medical genetics 2007, Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study., BMC medical genetics.
[PubMed 17903297]
Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.
Electrocardiography Daniel Levy et al. BMC medical genetics 2007, Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness., BMC medical genetics.
[PubMed 17903302]
These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96T66
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0009058 biosynthetic process GO:0009435 NAD biosynthetic process GO:0009611 response to wounding GO:0019363 pyridine nucleotide biosynthetic process GO:0019674 NAD metabolic process GO:0034628 'de novo' NAD biosynthetic process from aspartate
BC036218 - Homo sapiens nicotinamide nucleotide adenylyltransferase 3, mRNA (cDNA clone MGC:39688 IMAGE:5270916), complete cds. BC034374 - Homo sapiens nicotinamide nucleotide adenylyltransferase 3, mRNA (cDNA clone MGC:35390 IMAGE:5185621), complete cds. AK123208 - Homo sapiens cDNA FLJ41214 fis, clone BRALZ2016498, highly similar to Nicotinamide mononucleotide adenylyltransferase 3 (EC 2.7.7.1). AF345564 - Homo sapiens FKSG76 (FKSG76) mRNA, complete cds. BX649063 - Homo sapiens mRNA; cDNA DKFZp779J1439 (from clone DKFZp779J1439). AK127477 - Homo sapiens cDNA FLJ45569 fis, clone BRTHA3010469, highly similar to Nicotinamide mononucleotide adenylyltransferase 3 (EC 2.7.7.1). JD245537 - Sequence 226561 from Patent EP1572962. JD131304 - Sequence 112328 from Patent EP1572962. JD261058 - Sequence 242082 from Patent EP1572962. JD092437 - Sequence 73461 from Patent EP1572962. JD299235 - Sequence 280259 from Patent EP1572962. JD148701 - Sequence 129725 from Patent EP1572962. DQ890804 - Synthetic construct clone IMAGE:100003434; FLH166068.01X; RZPDo839C0686D nicotinamide nucleotide adenylyltransferase 3 (NMNAT3) gene, encodes complete protein. CU689864 - Synthetic construct Homo sapiens gateway clone IMAGE:100016787 5' read NMNAT3 mRNA. KJ896125 - Synthetic construct Homo sapiens clone ccsbBroadEn_05519 NMNAT3 gene, encodes complete protein. DQ893959 - Synthetic construct Homo sapiens clone IMAGE:100008419; FLH166064.01L; RZPDo839C0685D nicotinamide nucleotide adenylyltransferase 3 (NMNAT3) gene, encodes complete protein.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00760 - Nicotinate and nicotinamide metabolism hsa01100 - Metabolic pathways
Reactome (by CSHL, EBI, and GO)
Protein Q96T66 (Reactome details) participates in the following event(s):
R-HSA-200474 NMNAT3 transfers an adenylyl group from ATP to NAMN to yield NAAD R-HSA-196807 Nicotinate metabolism R-HSA-196849 Metabolism of water-soluble vitamins and cofactors R-HSA-196854 Metabolism of vitamins and cofactors R-HSA-1430728 Metabolism