1.14.14.17: squalene monooxygenase
This is an abbreviated version!
For detailed information about squalene monooxygenase, go to the full flat file.
Word Map on EC 1.14.14.17
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1.14.14.17
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cholesterol
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sterol
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terbinafine
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ergosterol
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trichophyton
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mevalonate
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lanosterol
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allylamine
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2,3-oxidosqualene
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hmg-coa
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itraconazole
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mentagrophytes
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rubrum
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oxidosqualene
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terbinafine-resistant
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tellurium
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tinea
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naftifine
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interdigitale
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antimycotic
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bloch
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griseofulvin
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dammarenediol
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dermatophytoses
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cycloartenol
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beta-amyrin
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medicine
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corporis
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drug development
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nutrition
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biotechnology
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pharmacology
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cholesterogenic
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synthesis
- 1.14.14.17
- cholesterol
- sterol
- terbinafine
- ergosterol
- trichophyton
- mevalonate
- lanosterol
- allylamine
- 2,3-oxidosqualene
- hmg-coa
- itraconazole
- mentagrophytes
- rubrum
- oxidosqualene
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terbinafine-resistant
- tellurium
- tinea
- naftifine
- interdigitale
-
antimycotic
-
bloch
-
griseofulvin
-
dammarenediol
-
dermatophytoses
- cycloartenol
- beta-amyrin
- medicine
-
corporis
- drug development
- nutrition
- biotechnology
- pharmacology
-
cholesterogenic
- synthesis
Reaction
Synonyms
CYP17, cytochrome P450 17alpha hydroxylase/17,20 lyase, EC 1.14.13.132, EC 1.14.99.7, Erg1, Erg1 protein, Erg1p, hydroxylase, squalene, oxygenase, squalene mono-, PgSQE1, PgSQE2, SE, SE1, SE3, SQE, SQE-I, SQE-II, sqe1, SQE3, SQLE, squalen expoxidase, squalene 2,3-epoxidase, squalene 2,3-oxidocyclase, squalene epoxidase, squalene epoxidase 1, squalene epoxidase 3, squalene hydroxylase, squalene mono-oxygenase, squalene oxydocyclase, squalene-2,3-epoxidase, squalene-2,3-epoxide cyclase, TkSQE1, TkSQE2, TkSQE3, TkSQE4
ECTree
1.14.14.17 squalene monooxygenaseAdvanced search results
results (
results (Engineering
Engineering on EC 1.14.14.17 - squalene monooxygenase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
L398F
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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
F203A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F223A
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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
F228A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F287A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F305A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F375A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F476A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F491A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F522A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F523A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K399F/R400F/D407F
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site-directed mutagenesis, triple mutant shows 10% of wild-type activity
K399P/R400P/D407P
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site-directed mutagenesis, triple mutant shows 10% of wild-type activity
Y194A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y209A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y334A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y473A
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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
Y493A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y528A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
D335F
D335P
D335W
E60A
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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
E60Q
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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
G210A
G25S
G30S
G345A
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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
G346A
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the mutant exhibits wild-type enzyme activity, steady-state protein levels, and naftifine and ketoconazole sensitivity, but is less sensitive toward terbinafine
G66A
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site-directed mutagenesis in the highly conserved motif 1, the mutant shows increased allylamine sensitivity compared to the wild-type enzyme
L37P
M348A
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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
R269
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site-directed mutagenesis, the mutant enzyme shows increased allylamine sensitivity
R269G
R340A
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site-directed mutagenesis in the highly conserved motif 2, the mutant enzyme shows highly reduced activity compared to the wild-type enzyme
L393F
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terbinafine-resistant strains/patient isolates all contain this missense point mutation responsible for the resistance to the drug
additional information
D335F
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random mutagenesis, mutation in the FADII site, inactive mutant
D335P
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random mutagenesis, mutation in the FADII site, inactive mutant
D335W
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random mutagenesis, mutation in the FADII site, inactive mutant
G210A
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random mutagenesis, mutation in the NB site, inactive mutant
G25S
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random mutagenesis, mutation in the FADI site, inactive mutant
G30S
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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
G30S
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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
L37P
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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
L37P
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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
R269G
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decrease in enzyme activity. Cells exhibit increased sensitivity to allylamines, but not to other ergosterol biosynthesis inhibitors
R269G
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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
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
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
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
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
additional information
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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
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
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
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
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
additional information
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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
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
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
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
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
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
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
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
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
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
additional information
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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
additional information
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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
additional information
Q9UNR6
a 12-residue region (residues Gln-62Leu-73), is required for cholesterol-mediated turnover
additional information
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a 12-residue region (residues Gln-62Leu-73), is required for cholesterol-mediated turnover
additional information
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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
additional information
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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
additional information
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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
additional information
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RNA interference of PgSQE1 in transgenic Panax ginseng plants completely suppresses PgSQE1 transcription. Concomitantly, the interference of PgSQE1 results in reduction of ginsenoside production
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
additional information
Q75W20
RNA interference of PgSQE1 in transgenic Panax ginseng plants completely suppresses PgSQE1 transcription. Concomitantly, the interference of PgSQE1 results in reduction of ginsenoside production
additional information
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amino acid substitutions in both highly conserved motifs 1 and 2 regions reduce enzyme activity and/or alter allylamine sensitivity, overview
additional information
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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
additional information
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mutations of amino acids belonging to the FAD I fingerprint motif, e.g. Gly27Ser and Gly30Ser, reduce the enzyme in vitro activity
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
additional information
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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
