Disease relevance of GFA1

• Using a genomic library constructed from Saccharomyces cerevisiae, we have identified a gene GFA1 that confers resistance to methylmercury toxicity [1].

High impact information on GFA1

• This functional activation was associated with the enhanced expression of functional antigens (GFA-1, GFA-2, and the receptor for C3bi) on eosinophils [2].
• Transformed yeast cells expressing GFA1 demonstrated resistance to methylmercury but no resistance to p-chloromercuribenzoate, a GFAT inhibitor [1].
• GFA1 encodes L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) and catalyzes synthesis of glucosamine-6-phosphate [1].
• GFAT as a target molecule of methylmercury toxicity in Saccharomyces cerevisiae [1].
• Additionally, Gfa1 will be a relevant target in therapeutic or physiological applications in which MetAP activity is inhibited [3].

Biological context of GFA1

• In the search for the mechanism by which GFA1 is activated in response to cell-wall perturbations, we could only show that neither MCM1 nor RLM1, which encode two transcriptional factors of the MADS box family that are required for expression of cell-cycle and cell-wall-related genes, was involved in this process [4].
• Southern hybridization indicated that a single GFA1 locus exists in the C. albicans genome [5].
• GFA1 encodes a predicted protein of 713 amino acids and is homologous to the corresponding gene from S. cerevisiae (72% identity at the nucleotide sequence level) as well as to the genes encoding glucosamine-6-phosphate synthases in bacteria and vertebrates [5].
• The W303B/pGFA1 strain did not show resistance to mercuric chloride, zinc chloride, cadmium chloride or copper chloride, suggesting that the resistance acquired by GFA1 gene transfection might be specific to MeHg [6].
• As expected HAP4, GFA1 and LAP4 genes have been found and six new open reading frames (ORFs) with a coding capacity of more than 100 amino acid residues have been identified [7].

Anatomical context of GFA1

• Involvement of GFA1, which encodes glutamine-fructose-6-phosphate amidotransferase, in the activation of the chitin synthesis pathway in response to cell-wall defects in Saccharomyces cerevisiae [4].

Associations of GFA1 with chemical compounds

• Finally, the stimulation of chitin production was also accompanied by an increase in pools of fructose 6-Phosphate, a substrate of Gfa1p [4].
• Candida albicans glucosamine-6-phosphate (GlcN-6-P) synthase was purified to apparent homogeneity with 52% yield from recombinant yeast YRSC-65 cells efficiently overexpressing the GFA1 gene [8].
• Considering that GFAT is an essential cellular enzyme, our findings suggest that GFAT is the major target molecule of methylmercury in yeasts [1].
• Yeast glutamine-fructose-6-phosphate aminotransferase (Gfa1) requires methionine aminopeptidase activity for proper function [3].
• GFA1 was reported to encode L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) which catalyzes the synthesis of glucosamine-6-phosphate from glutamine and fructose-6-phosphate [6].

Regulatory relationships of GFA1

• Glc7p protein phosphatase inhibits expression of glutamine-fructose-6-phosphate transaminase from GFA1 [9].
• One or more phosphorylated proteins activate GFA1 transcription because the pheromone response and Pkc1p/mitogen-activated protein kinase pathways positively regulate GFA1 transcription [9].

Other interactions of GFA1

• Overexpression of GFA1 caused an approximately threefold increase in chitin in the transformed cells, whereas chitin content was barely affected by the joint overexpression of CHS3 and CHS7 [4].
• Our findings show that an I-1-sensitive Glc7p holoenzyme reduces GFA1 transcription [9].
• The gene (the gene should be called GFA1 for glutamine:fructose-6-phosphate amidotransferase) for the enzyme has been cloned by complementing the gcn1 mutation (Whelan, W. L., and Ballou, C. E. (1975) J. Bacteriol. 125, 1545-1557) [10].
• It covers the HAP4-GFA1-LAP4 loci already described [7].

References