Human Gene NMNAT3 (uc003etj.3)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:139,279,023-139,346,606)mRNA (may differ from genome)Protein (252 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeUniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  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:
  1. 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.
  2. 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.

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.60 RPKM in Testis
Total median expression: 127.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -10.3040-0.257 Picture PostScript Text
3' UTR -245.60829-0.296 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004820 - Cytidylyltransf
IPR005248 - NAMN_adtrnsfrase
IPR014729 - Rossmann-like_a/b/a_fold

Pfam Domains:
PF01467 - Cytidylyltransferase-like

SCOP Domains:
52374 - Nucleotidylyl transferase

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1NUP - X-ray MuPIT 1NUQ - X-ray MuPIT 1NUR - X-ray MuPIT 1NUS - X-ray MuPIT 1NUT - X-ray MuPIT 1NUU - X-ray MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologGenome BrowserNo ortholog
Gene Details   Gene Details 
Gene Sorter   Gene Sorter 
  Ensembl WormBase 
  Protein Sequence Protein Sequence 
  Alignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000309 nicotinamide-nucleotide adenylyltransferase activity
GO:0003824 catalytic activity
GO:0004515 nicotinate-nucleotide adenylyltransferase activity
GO:0005524 ATP binding
GO:0016740 transferase activity
GO:0016779 nucleotidyltransferase activity

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

Cellular Component:
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix


-  Descriptions from all associated GenBank mRNAs
  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

-  Other Names for This Gene
  Alternate Gene Symbols: AF345564, B3KVR6, D3DNF2, D3DNF3, FKSG76, NMNA3_HUMAN, NM_178177, NP_835471, Q8N4G1, Q96T66
UCSC ID: uc003etj.3
RefSeq Accession: NM_178177
Protein: Q96T66 (aka NMNA3_HUMAN or NMA3_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AF345564.1
exon count: 4CDS single in 3' UTR: no RNA size: 1223
ORF size: 759CDS single in intron: no Alignment % ID: 99.92
txCdsPredict score: 1711.00frame shift in genome: no % Coverage: 99.92
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.