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Gene Review

AFR1  -  Afr1p

Saccharomyces cerevisiae S288c

Synonyms: D4471, Protein AFR1, YDR085C
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Disease relevance of AFR1


High impact information on AFR1

  • AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae [2].
  • A plasmid overexpression strategy was used to isolate a new gene, AFR1, which acts together with the receptor C terminus to promote adaptation [3].
  • Functional analysis of the interaction between Afr1p and the Cdc12p septin, two proteins involved in pheromone-induced morphogenesis [4].
  • Saccharomyces cerevisiae mating pheromones induce production of Afr1p, a protein that negatively regulates pheromone receptor signaling and is required for normal formation of the projection of cell growth that becomes the site of cell fusion during conjugation [4].
  • We have recently demonstrated that upregulation of the ATP binding cassette (ABC) transporter-encoding gene AFR1 in Cryptococcus neoformans is involved in the in vitro resistance to fluconazole of this yeast [1].

Biological context of AFR1

  • The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis [2].
  • The mutant genes contained four distinct point mutations that all occurred between codons 254 and 263, identifying a region that is critical for AFR1 function [5].
  • However, AFR1 overexpression did not detectably influence receptor endocytosis or the stability of the receptor protein [6].
  • AFR1 overexpression diminished signaling in a strain that lacks the C-terminal phosphorylation sites of the receptor, indicating that AFR1 acts independently of phosphorylation [6].
  • Instead, gene dosage studies showed that the effects of AFR1 overexpression on signaling were inversely proportional to the number of receptors [6].

Associations of AFR1 with chemical compounds

  • These findings indicate that the upregulation of the AFR1 gene is an important factor in either determining the in vivo resistance to fluconazole or influencing the virulence of C. neoformans [1].

Regulatory relationships of AFR1

  • The AFR1 mutants were also defective when expressed as fusions to STE2, the alpha-factor receptor, indicating that the mutant Afr1 proteins are defective in function and not in co-localizing with receptors [5].

Other interactions of AFR1

  • AFR1 also showed an interesting genetic relationship with the alpha-factor receptor gene, STE2, suggesting that the receptor is regulated by Afr1p [6].
  • Analysis of axl1Delta in combination with other mutations that cause defects in morphogenesis or pheromone sensitivity (e.g. bar1, sst2, afr1) indicated that both phenotypes of ste2-T326 cells, supersensitivity to alpha-factor and the defect in forming pointed projections, contributed to the synergistic mating defect [7].
  • Gpa1-mediated adaptation appears to be independent of Afr1, Akr1, and the carboxy-terminus of the pheromone receptor [8].


  1. Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans. Sanguinetti, M., Posteraro, B., La Sorda, M., Torelli, R., Fiori, B., Santangelo, R., Delogu, G., Fadda, G. Infect. Immun. (2006) [Pubmed]
  2. AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae. Konopka, J.B., DeMattei, C., Davis, C. Mol. Cell. Biol. (1995) [Pubmed]
  3. AFR1 acts in conjunction with the alpha-factor receptor to promote morphogenesis and adaptation. Konopka, J.B. Mol. Cell. Biol. (1993) [Pubmed]
  4. Functional analysis of the interaction between Afr1p and the Cdc12p septin, two proteins involved in pheromone-induced morphogenesis. Giot, L., Konopka, J.B. Mol. Biol. Cell (1997) [Pubmed]
  5. Point mutations identify a conserved region of the saccharomyces cerevisiae AFR1 gene that is essential for both the pheromone signaling and morphogenesis functions. DeMattei, C.R., Davis, C.P., Konopka, J.B. Genetics (2000) [Pubmed]
  6. Afr1p regulates the Saccharomyces cerevisiae alpha-factor receptor by a mechanism that is distinct from receptor phosphorylation and endocytosis. Davis, C., Dube, P., Konopka, J.B. Genetics (1998) [Pubmed]
  7. Combining mutations in the incoming and outgoing pheromone signal pathways causes a synergistic mating defect in Saccharomyces cerevisiae. Giot, L., DeMattei, C., Konopka, J.B. Yeast (1999) [Pubmed]
  8. The yeast pheromone-responsive G alpha protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus. Zhou, J., Arora, M., Stone, D.E. Cell Biochem. Biophys. (1999) [Pubmed]
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