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Gene Review

ADE3  -  trifunctional formate-tetrahydrofolate...

Saccharomyces cerevisiae S288c

Synonyms: C-1-tetrahydrofolate synthase, cytoplasmic, C1-THF synthase, G7733, YGR204W
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Disease relevance of ADE3

  • These results are also consistent with those obtained in heterologous expression of spinach and Clostridium acidiurici monofunctional synthetases in ade3 strains [1].

High impact information on ADE3

  • This hypothesis is based on their finding that the presence of the full-length ADE3 C1-THF synthase, whether catalytically active or not, is correlated with the Ade+ phenotype [1].
  • In contrast to their results, our deletion analysis of the ADE3 gene indicates that the presence of either the synthetase or dehydrogenase/cyclohydrolase domains of C1-THF synthase is enough to complement the adenine requirement in ade3 strains [1].
  • Clones were isolated that complement mutations in the yeast ADE2, ADE3, and ADE8 genes [2].
  • RSR1 maps between CDC62 and ADE3 on the right arm of chromosome VII; its predicted product is approximately 50% identical to other proteins in the ras family [3].
  • Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements [4].

Chemical compound and disease context of ADE3

  • Heterologous expression of the Clostridium acidiurici gene encoding a monofunctional 10-formyl-THF synthetase in an ade3 deletion strain did not restore growth in the absence of adenine, even though the monofunctional synthetase was catalytically competent in vivo [5].
  • The feasibility and versatility of the method is shown with the yeast ADE3 gene encoding the cytoplasmic C1-THF synthase and the gene encoding the monofunctional 10-formyl-THF synthetase from Clostridium acidiurici [6].

Biological context of ADE3

  • Frequently, the plasmid carries the ADE3 gene and mutants are recognized as red colonies that fail to produce sectors [7].
  • In addition, we report the identification of a truncated ADE3 allele with a unique coloration phenotype and show that it can be used to improve synthetic lethal screens [7].
  • Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes [7].
  • An unusual open reading frame that is encoded by a very unbiased set of codons follows the ADE3 gene [8].
  • Nucleotide sequence of the Saccharomyces cerevisiae ADE3 gene encoding C1-tetrahydrofolate synthase [8].

Anatomical context of ADE3


Associations of ADE3 with chemical compounds

  • Nonetheless, point mutants of Shm2p that were catalytically inactive (i.e. failed to rescue the methionine auxotrophy of a shm2Delta ade3 strain) complemented the synthetic lethal phenotype, thus revealing a novel metabolism-independent function of Shm2p [10].
  • Shm2p and Ade3p are cytoplasmic enzymes producing 5,10-methylene tetrahydrofolate in convergent pathways as the primary source for cellular one-carbon groups [10].
  • The effect of mutations in LPD1 (L-subunit of GDC), SER1 (synthesis of serine from 3-phosphoglycerate), ADE3 (cytoplasmic synthesis of one-carbon units for the serine synthesis from glycine), and all combinations of each has been determined [11].
  • In the present work, site-directed mutagenesis of the S. cerevisiae ADE3 gene, which encodes C1-THF synthase, was used to individually change each cysteine contained within the dehydrogenase/cyclohydrolase domain (Cys-11, Cys-144, and Cys-257) to serine [12].
  • This trifunctional enzyme, encoded by the ADE3 gene in the yeast Saccharomyces cerevisiae, is thought to be responsible for the synthesis of the one-carbon donor 10-formyl-THF for de novo purine synthesis [5].

Regulatory relationships of ADE3


Other interactions of ADE3


Analytical, diagnostic and therapeutic context of ADE3

  • Determination of the amount of C1-THF synthase mRNA under the various growth conditions by an in vitro translation/immunoprecipitation assay indicates that regulation of the enzyme occurs predominantly at a pretranslational level since steady-state levels of C1-THF synthase mRNA are 2-3-fold higher in derepressed cells than in repressed cells [19].


  1. Function of yeast cytoplasmic C1-tetrahydrofolate synthase. Song, J.M., Rabinowitz, J.C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  2. Cloning of three human multifunctional de novo purine biosynthetic genes by functional complementation of yeast mutations. Schild, D., Brake, A.J., Kiefer, M.C., Young, D., Barr, P.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1. Bender, A., Pringle, J.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  4. Identification and characterization of a sequence motif involved in nonsense-mediated mRNA decay. Zhang, S., Ruiz-Echevarria, M.J., Quan, Y., Peltz, S.W. Mol. Cell. Biol. (1995) [Pubmed]
  5. Molecular genetic analysis of Saccharomyces cerevisiae C1-tetrahydrofolate synthase mutants reveals a noncatalytic function of the ADE3 gene product and an additional folate-dependent enzyme. Barlowe, C.K., Appling, D.R. Mol. Cell. Biol. (1990) [Pubmed]
  6. A general method for generation and analysis of defined mutations in enzymes involved in a tetrahydrofolate-interconversion pathway. Barlowe, C.K., Appling, D.R. Biofactors (1989) [Pubmed]
  7. Pitfalls of the synthetic lethality screen in Saccharomyces cerevisiae: an improved design. Koren, A., Ben-Aroya, S., Steinlauf, R., Kupiec, M. Curr. Genet. (2003) [Pubmed]
  8. Nucleotide sequence of the Saccharomyces cerevisiae ADE3 gene encoding C1-tetrahydrofolate synthase. Staben, C., Rabinowitz, J.C. J. Biol. Chem. (1986) [Pubmed]
  9. In vivo analysis of folate coenzymes and their compartmentation in Saccharomyces cerevisiae. McNeil, J.B., Bognar, A.L., Pearlman, R.E. Genetics (1996) [Pubmed]
  10. Genetic interaction between a chaperone of small nucleolar ribonucleoprotein particles and cytosolic serine hydroxymethyltransferase. Yang, Y., Meier, U.T. J. Biol. Chem. (2003) [Pubmed]
  11. Genetics of the synthesis of serine from glycine and the utilization of glycine as sole nitrogen source by Saccharomyces cerevisiae. Sinclair, D.A., Dawes, I.W. Genetics (1995) [Pubmed]
  12. Site-directed mutagenesis of yeast C1-tetrahydrofolate synthase: analysis of an overlapping active site in a multifunctional enzyme. Barlowe, C.K., Williams, M.E., Rabinowitz, J.C., Appling, D.R. Biochemistry (1989) [Pubmed]
  13. The detection of monosomic colonies produced by mitotic chromosome non-disjunction in the yeast Saccharomyces cerevisiae. Parry, J.M., Zimmerman, F.K. Mutat. Res. (1976) [Pubmed]
  14. The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase. Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A., Flint, D.H. Arch. Biochem. Biophys. (1994) [Pubmed]
  15. The histidine permease gene (HIP1) of Saccharomyces cerevisiae. Tanaka, J., Fink, G.R. Gene (1985) [Pubmed]
  16. Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae. Nigavekar, S.S., Cannon, J.F. Yeast (2002) [Pubmed]
  17. Synthetic lethal screen. Barbour, L., Xiao, W. Methods Mol. Biol. (2006) [Pubmed]
  18. Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase isozymes from Saccharomyces cerevisiae. Tibbetts, A.S., Appling, D.R. J. Biol. Chem. (2000) [Pubmed]
  19. Regulation of expression of the ADE3 gene for yeast C1-tetrahydrofolate synthase, a trifunctional enzyme involved in one-carbon metabolism. Appling, D.R., Rabinowitz, J.C. J. Biol. Chem. (1985) [Pubmed]
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