title: The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase.
abstract: In Saccharomyces cerevisiae, mutations in FKS1 confer hypersensitivity to the immunosuppressants FK506 and cyclosporin A, while mutations in ETG1 confer resistance to the cell-wall-active echinocandins (inhibitors of 1,3-beta-D-glucan synthase) and, in some cases, concomitant hypersensitivity to the chitin synthase inhibitor nikkomycin Z. The FKS1 and ETG1 genes were cloned by complementation of these phenotypes and were found to be identical. Disruption of the gene results in (i) a pronounced slow-growth phenotype, (ii) hypersensitivity to FK506 and cyclosporin A, (iii) a slight increase in sensitivity to echinocandin, and (iv) a significant reduction in 1,3-beta-D-glucan synthase activity in vitro. The nucleotide sequence encodes a 215-kDa polypeptide predicted to be an integral membrane protein with 16 transmembrane helices, consistent with previous observations that the etg1-1 mutation results in echinocandin-resistant glucan synthase activity associated with the nonextractable membrane fraction of the enzyme. These results suggest that FKS1 encodes a subunit of 1,3-beta-D-glucan synthase. The residual activity present in the disruption mutant, the nonessential nature of the gene, and results of Southern blot hybridization analysis point to the existence of a glucan synthase isozyme.
authors.affiliation: Merck Research Laboratoies, Rohway, NJ 07065.
authors.forename: C M
authors.initials: CM
authors.lastname: Douglas
authors.forename: F
authors.initials: F
authors.lastname: Foor
authors.forename: J A
authors.initials: JA
authors.lastname: Marrinan
authors.forename: N
authors.initials: N
authors.lastname: Morin
authors.forename: J B
authors.initials: JB
authors.lastname: Nielsen
authors.forename: A M
authors.initials: AM
authors.lastname: Dahl
authors.forename: P
authors.initials: P
authors.lastname: Mazur
authors.forename: W
authors.initials: W
authors.lastname: Baginsky
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: el-Sherbeini
mesh_terms: D001483:Base Sequence; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000235:genetics; D005800:Genes, Fungal; D005964:Glucosyltransferases / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D002148:Calmodulin-Binding Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D005964:Glucosyltransferases; C040232:glucan synthase; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus