NMA2/YGR010W Summary Help

Standard Name NMA2 1
Systematic Name YGR010W
Feature Type ORF, Verified
Description Nicotinic acid mononucleotide adenylyltransferase; catalyzes the transfer of the adenylyl moiety of ATP to nicotinamide mononucleotide to form NAD; involved in de novo and salvage synthesis of NAD(+); homolog of human NMNAT; NMA2 has a paralog, NMA1, that arose from the whole genome duplication (1, 2, 3, 4 and see Summary Paragraph)
Name Description Nicotinamide Mononucleotide Adenylyltransferase 1
Chromosomal Location
ChrVII:511545 to 512732 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All NMA2 GO evidence and references
  View Computational GO annotations for NMA2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 43 genes
Resources
Pathways
Classical genetics
overexpression
Large-scale survey
null
Resources
29 total interaction(s) for 17 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 1
  • Two-hybrid: 9

Genetic Interactions
  • Negative Genetic: 9
  • Positive Genetic: 3
  • Synthetic Growth Defect: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 395
Molecular Weight (Da) 44,909
Isoelectric Point (pI) 5.78
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:511545 to 512732 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1188 511545..512732 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003242
SUMMARY PARAGRAPH for NMA2

About NAD biosynthesis -- de novo and salvage pathways

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for cellular redox reactions and energy metabolism. NAD also has been shown to be an important substrate in a variety of biological processes, including transcriptional regulation, DNA repair, calcium-dependent signaling pathways, calorie-restriction-mediated life-span extension and age-associated diseases (5, 6). NAD appears to affect these processes by regulating the Sir2p family of NAD-dependent deacetylases (Sirtuins) (6).

There are a number of pathways for NAD biosynthesis. In yeast and most other organisms, the two major pathways are de novo synthesis of NAD (the de novo pathway) and regeneration of NAD from its nicotinamide degradation products (the NAD salvage pathway) (7, 6). NAD is synthesized de novo from tryptophan via kynurenine (7). In this pathway tryptophan is converted to nicotinic acid mononucleotide (NaMN) in 6 enzymatic steps (catalyzed by Bna1-2p, and Bna4-7p) and one non-enzymatic step (7). At NaMN the de novo pathway converges with the NAD salvage pathway and the last two steps to NAD are shared (7, 6). In the yeast NAD salvage pathway, the vitamin precursors nicotinamide and nicotinic acid are converted to NaMN, the point of convergence with the de novo pathway (6). The steps from nicotinic acid to NAD were elucidated by Preiss and Handler and are sometimes referred to as the Preiss-Handler pathway (as reviewed in 8). Yeast can also import extracellular nicotinic acid into the cell by the permease Tna1p and then convert it to NAD via the Preiss-Handler pathway (6).

There are four additional pathways for synthesizing NAD in yeast: two salvage pathways from the vitamin precursor nicotinamide riboside (NR) and two salvage pathways from nicotinic acid riboside (NaR) (8, 9, 10). Only one of these pathways, the NR salvage pathway I, is independent of the NAD salvage pathway. In the NR salvage pathway I, NR is phosphorylated to nicotinamide mononucleotide by the kinase Nrk1p, and then adenylated to NAD by Nma1p or Nma2p (8). In the NR salvage pathway II, the hydrolase Urh1p or the phosphorylase Pnp1p split NR into a ribosyl product and nicotinamide, which subsequently is converted to NAD via the NAD salvage pathway (9). The initial steps in the NaR salvage pathways I and II are similar to those of the NR salvage pathways I and II and are catalyzed by the same enzymes, respectively. In the NaR salvage pathway I, Nrk1p phosphorylates NaR to NaMN, which subsequently is converted to NAD via the enzymes shared by the de novo and NAD salvage pathways (10). In the NaR salvage pathway II, Urh1p or Pnp1p split NR into a ribosyl product and nicotinic acid, which is first converted to NaMN and then is converted similarly to NAD (10).

Last updated: 2008-03-06 Contact SGD

References cited on this page View Complete Literature Guide for NMA2
1) Anderson RM, et al.  (2002) Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem 277(21):18881-90
2) Emanuelli M, et al.  (1999) Identification and characterization of YLR328W, the Saccharomyces cerevisiae structural gene encoding NMN adenylyltransferase. Expression and characterization of the recombinant enzyme. FEBS Lett 455(1-2):13-7
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Ocampo A, et al.  (2013) NAD+ salvage pathway proteins suppress proteotoxicity in yeast models of neurodegeneration by promoting the clearance of misfolded/oligomerized proteins. Hum Mol Genet 22(9):1699-708
5) Anderson RM, et al.  (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423(6936):181-5
6) Lin SJ and Guarente L  (2003) Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol 15(2):241-6
7) Bedalov A, et al.  (2003) NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae. Mol Cell Biol 23(19):7044-54
8) Bieganowski P and Brenner C  (2004) Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell 117(4):495-502
9) Belenky P, et al.  (2007) Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell 129(3):473-84
10) Tempel W, et al.  (2007) Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD(+). PLoS Biol 5(10):e263