1.14.14.17 D335F mutation in FAD II binding site, nonfunctional enzyme 671379 1.14.14.17 D335F random mutagenesis, mutation in the FADII site, inactive mutant 671379 1.14.14.17 D335P mutation in FAD II binding site, nonfunctional enzyme 671379 1.14.14.17 D335P random mutagenesis, mutation in the FADII site, inactive mutant 671379 1.14.14.17 D335W mutation in FAD II binding site, nonfunctional enzyme 671379 1.14.14.17 D335W random mutagenesis, mutation in the FADII site, inactive mutant 671379 1.14.14.17 D407F site-directed mutagenesis, mutant shows 8% of wild-type activity 657764 1.14.14.17 E60A site-directed mutagenesis in the highly conserved motif 1, the E60A variant poorly complements growth of KLN1, and shows reduced activity and about 50fold increased sensitivity to terbinafine and naftifine and 5fold to ketoconazole compared to that in the wild type, and confers temperature-sensitive growth 684491 1.14.14.17 E60Q site-directed mutagenesis in the highly conserved motif 1, the E60A variant poorly complements growth of KLN1, and shows highly reduced activity and about 50fold increased sensitivity to terbinafine and naftifine and 5fold to ketoconazole compared to that in the wild type, and confers temperature-sensitive growth 684491 1.14.14.17 F203A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F223A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, the F223A mutant no longer accepts (3S)2,3-oxidosqualene as a substrate 684828 1.14.14.17 F228A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F287A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F305A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F35A/S37A/L65A/I69A mutant displays blunted cholesterol regulation 745376 1.14.14.17 F375A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F402L the point mutation causes terbinafine resistance 715725 1.14.14.17 F420L the point mutation causes terbinafine resistance 715725 1.14.14.17 F430S the point mutation causes terbinafine resistance 715725 1.14.14.17 F476A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F491A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F522A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 F523A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 G210A mutation in nucleotide binding site, nonfunctional enzyme 671379 1.14.14.17 G210A random mutagenesis, mutation in the NB site, inactive mutant 671379 1.14.14.17 G25S mutation in FAD I binding site, nonfunctional enzyme 671379 1.14.14.17 G25S random mutagenesis, mutation in the FADI site, inactive mutant 671379 1.14.14.17 G30S decrease in enzyme activity, sevenfold increase in enzyme mRNA level. Cells exhibit altered sterol composition and increased sensitivity to allylamines and other ergosterol biosynthesis inhibitors 671379 1.14.14.17 G30S random mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme, but a 7fold increased erg1 mRNA level and altered ergosterol composotion, the mutation renders KLN1 more sensitive not only to allylamines but also to other ergosterol biosynthesis inhibitors 671379 1.14.14.17 G345A site-directed mutagenesis, the mutation of the highly conserved motif 2 results in increased allylamine sensitivity without cross-sensitivity to ketoconazole, decreased enzyme activity, and induced Erg1p levels compared to the wild-type enzyme 684491 1.14.14.17 G346A the mutant exhibits wild-type enzyme activity, steady-state protein levels, and naftifine and ketoconazole sensitivity, but is less sensitive toward terbinafine 684491 1.14.14.17 G66A site-directed mutagenesis in the highly conserved motif 1, the mutant shows increased allylamine sensitivity compared to the wild-type enzyme 684491 1.14.14.17 K399F site-directed mutagenesis, mutant shows 28% of wild-type activity 657764 1.14.14.17 K399F/R400F/D407F site-directed mutagenesis, triple mutant shows 10% of wild-type activity 657764 1.14.14.17 K399P/R400P/D407P site-directed mutagenesis, triple mutant shows 10% of wild-type activity 657764 1.14.14.17 K399W/R400W/D407W site-directed mutagenesis, inactive mutant 657764 1.14.14.17 L251F the point mutation causes terbinafine resistance 715725 1.14.14.17 L37P decrease in enzyme activity, sevenfold increase in enzyme mRNA level. Cells exhibit altered sterol composition and increased sensitivity to allylamines and other ergosterol biosynthesis inhibitors 671379 1.14.14.17 L37P random mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme, but a 7fold increased erg1 mRNA level and altered ergosterol composotion, the mutation renders KLN1 more sensitive not only to allylamines but also to other ergosterol biosynthesis inhibitors 671379 1.14.14.17 L393F terbinafine-resistant strains/patient isolates all contain this missense point mutation responsible for the resistance to the drug 657561 1.14.14.17 L398F site-directed mutagenesis, introduction of the mutation equivalent to L393F found in terbinafine-resistant Trichophyton rubrum strains, mutation renders Saccharomyces cerevisiae strain INVSc1 expressing the recombinant Candida albicans enzyme insensitive to terbafine 657561 1.14.14.17 L42A mutant displays blunted cholesterol regulation 745376 1.14.14.17 M348A site-directed mutagenesis in the highly conserved motif 2, the mutant is more sensitive toward terbinafine and naftifine and slightly more sensitive toward ketoconazole compared to the wild-type enzyme, while enzyme activity is reduced and protein levels are induced 684491 1.14.14.17 additional information a 12-residue region (residues Gln-62–Leu-73), is required for cholesterol-mediated turnover 745376 1.14.14.17 additional information amino acid substitutions in both highly conserved motifs 1 and 2 regions reduce enzyme activity and/or alter allylamine sensitivity, overview 684491 1.14.14.17 additional information construction of a disruption mutant of both gene ERG1 alleles, which is lethal, and of a heterozygous ERG1 disruptant mutant by disruption of one ERG1 allele, while the second is controlled by the regulable promotor MET3p repressable by methionine and cysteine, the heterozyygous mutant strain does not produce ergosterol, conditional mutant shows reduced passive diffusion of drug into the cells, hyphal morphogenesis is affected in the mutant, overview 658999 1.14.14.17 additional information construction of a truncated enzyme mutant 657764 1.14.14.17 additional information construction of mutant transgenic plants with defective isozyme SQ1 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotypes, overview 687556 1.14.14.17 additional information construction of mutant transgenic plants with defective isozyme SQ2 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotype, overview 687556 1.14.14.17 additional information construction of mutant transgenic plants with defective isozyme SQ3 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway. Homozygous sqe1-3 plants are completely infertile whether grown in soil or hydroponically. eed pods of sqe1-3 plants grown hydroponically elongated nearly normally, but sqe1-3 siliques are slightly thinner than wild type and contained shriveled, inviable seeds, phenotypes, overview 687556 1.14.14.17 additional information construction of mutant transgenic plants with defective isozyme SQ4 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotypes, overview 687556 1.14.14.17 additional information erg1 silencing in Hypholoma sublateritium, by expression of constructions using the gdh promoter of Agaricus bisporus, results in an ergosterol-dependnet phenotype for full growth, overexpression of erg1 results in 32%-97% increment of clavaric acid production, overview 686043 1.14.14.17 additional information identification of single nucleotide polymorphism c.2565 G>T in Berkshire pigs. Homozygous GG pigs express more squalene epoxidase mRNA than GT heterozygous and TT homozygous pigs in longissimus dorsi tissue. The single nucleotide polymorphism is associated with several meat quality traits including backfat thickness, carcass weight, meat colour (yellowness), fat composition, and water-holding capacity 746469 1.14.14.17 additional information in hepatocytes deficent for NADPH-cytochrome P450 reductase, the second microsomal reductase retains about 40% of the full activity for conversion of squalene to 2,3(s)-oxidosqualene with squalene monooxygenase, overview 684673 1.14.14.17 additional information isolation of erg1 allele mutants that confer increased terbinafine sensitivity or that show a lethal phenotype when they are expressed in erg1-knockout strain KLN1, overview 671379 1.14.14.17 additional information knockout of cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 shows dramatically reduced de novo synthesis of steroids, e.g. progesterone, which can partially be rescued by transfection of CYP17, the latter cells can synthesize progesterone if supplemented with precusors squalene epoxide, lanosterol, zymosterol, and desmosterol, but not squalene 659953 1.14.14.17 additional information mutations of amino acids belonging to the FAD I fingerprint motif, e.g. Gly27Ser and Gly30Ser, reduce the enzyme in vitro activity 715725 1.14.14.17 additional information RNA interference of PgSQE1 in transgenic Panax ginseng plants completely suppresses PgSQE1 transcription. Concomitantly, the interference of PgSQE1 results in reduction of ginsenoside production 700657 1.14.14.17 R269 site-directed mutagenesis, the mutant enzyme shows increased allylamine sensitivity 684491 1.14.14.17 R269G decrease in enzyme activity. Cells exhibit increased sensitivity to allylamines, but not to other ergosterol biosynthesis inhibitors 671379 1.14.14.17 R269G random mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme and a 5-10fold increase in allylamine sensitivity but no cross-sensitivity to the other ergosterol biosynthesis inhibitors 671379 1.14.14.17 R340A site-directed mutagenesis in the highly conserved motif 2, the mutant enzyme shows highly reduced activity compared to the wild-type enzyme 684491 1.14.14.17 R400F site-directed mutagenesis, mutant shows 24% of wild-type activity 657764 1.14.14.17 S43A mutant displays normal cholesterol regulation 745376 1.14.14.17 V41A mutant displays normal cholesterol regulation 745376 1.14.14.17 Y194A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 Y209A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 Y334A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 Y473A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, the mutant converts (3S)2,3-oxidosqualene to (3S,22S)2,3-22,23-dioxidosqualene twice more efficiently than wild-type enzyme 684828 1.14.14.17 Y493A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828 1.14.14.17 Y528A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme 684828