Molecular Cloning and Expression of Rat Squalene Epoxidase (*)

Squalene epoxidase (SE) (EC 1.14.99.7) catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway. Rat SE cDNA was isolated by selecting yeast transformants expressing rat cDNA in the presence of terbinafine, an inhibitor specific for fungal SE. The expression of rat SE in the isolated terbinafine-resistant clone was confirmed by its survival in the presence of either terbinafine or an inhibitor specific for mammalian SE, NB-598, but not in the presence of both terbinafine and NB-598. Rat SE polypeptide deduced from the nucleotide sequence contains 573 amino acids, and its molecular weight is 63,950 Da. The amino acid sequence reveals one potential transmembrane domain, a hydrophobic segment (Leu to Tyr) in the NH2-terminal region. This region also contains a β1-αA-β2 motif, which is the consensus sequence for an FAD binding domain, suggesting that SE is a flavoenzyme. This deduced rat SE sequence is 30.2% identical to the ERG 1 gene, which encodes SE from an allylamine-resistant Saccharomycescerevisiae mutant. Expression of a full-length rat SE protein in Escherichia coli confirms this polypeptide as a functional SE. This is the first report of the molecular cloning of mammalian SE.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-01-06

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.270.1.17PMID 7814369
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Squalene Dioxide Pathway of Steroid Biosynthesis

  1994cited by this paper
• Cholesterol and the Golgi apparatus.

  1993cited by this paper
• Ras C-terminal processing enzymes--new drug targets?

  1991cited by this paper
• The gene encoding squalene epoxidase from Saccharomyces cerevisiae: cloning and characterization.

  1991cited by this paper
• Regulation of squalene epoxidase activity in rat liver.

  1990cited by this paper
• Regulation of squalene epoxidase in HepG2 cells.

  1990cited by this paper
• NB-598: a potent competitive inhibitor of squalene epoxidase.

  1990cited by this paper
• Regulation of the mevalonate pathway

  1990cited by this paper
• High-frequency transformation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of Schizosaccharomyces pombe.

  1990cited by this paper
• Juvenile hormone bisepoxide biosynthesis in vitro by the ring gland of Drosophila melanogaster: a putative juvenile hormone in the higher Diptera.

  1989cited by this paper
• Effects of 2, 3-iminosqualene on cultured cells

  1987cited by this paper
• Vectors for selective expression of cloned DNAs by T7 RNA polymerase.

  1987cited by this paper
• An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.

  1987cited by this paper
• Prediction of the occurrence of the ADP-binding beta alpha beta-fold in proteins, using an amino acid sequence fingerprint.

  1986cited by this paper
• Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.

  1986cited by this paper
• Prediction of the Occurrence of the ADP-binding βαβ-fold in Proteins, Using an Amino Acid Sequence Fingerprint

  1986cited by this paper
• Inhibition of squalene epoxidase by allylamine antimycotic compounds. A comparative study of the fungal and mammalian enzymes.

  1985cited by this paper
• Squalene epoxidase from rat liver microsomes.

  1985cited by this paper
• Identification of regulatory oxysterols, 24(S),25-epoxycholesterol and 25-hydroxycholesterol, in cultured fibroblasts.

  1985cited by this paper
• FAD-binding site of glutathione reductase.

  1982cited by this paper
• A simple method for displaying the hydropathic character of a protein.

  1982cited by this paper
• Purification and partial characterization of squalene epoxidase from rat liver microsomes.

  1982cited by this paper
• Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide.

  1981cited by this paper
• Two major regulatory steps in cholesterol synthesis by human renal cancer cells.

  1979cited by this paper
• Inhibition of cholesterol biosynthesis in Chinese hamster ovary cells by 4,4,10 beta-trimethyl-trans-decal-3 beta-ol. A specific 2,3-oxidosqualene cyclase inhibitor.

  1979cited by this paper
• A novel inhibitor of steroid biosynthesis [11]

  1978cited by this paper
• Yeast mutants deficient in heme biosynthesis and a heme mutant additionally blocked in cyclization of 2,3-oxidosqualene.

  1977cited by this paper
• Solubilization and partial characterization of rat liver squalene epoxidase.

  1975cited by this paper
• Yeast mutants requiring ergosterol as only lipid supplement.

  1974cited by this paper
• Squalene epoxidase of rat liver.

  1972cited by this paper
• Studies on squalene epoxidase of rat liver.

  1970cited by this paper

• Squalene Epoxidase: A Key Enzymatic Component in the Triterpenoid Biosynthesis Pathway.

  2026cites this paper
• In-gel refolding allows fluorescence detection of fully denatured GFPs after SDS-PAGE

  2024cites this paper
• Mining and modification of Oryza sativa-derived squalene epoxidase for improved β-amyrin production in Saccharomyces cerevisiae.

  2023cites this paper
• Flavoprotein monooxygenases: Versatile biocatalysts.

  2021cites this paper
• Squalene monooxygenase: a journey to the heart of cholesterol synthesis.

  2020cites this paper
• Molecular basis of triterpene-based chemophenetics in ferns

  2020cites this paper
• The Degron Architecture of Squalene Monooxygenase and How Specific Lipids Calibrate Levels of This Key Cholesterol Synthesis Enzyme.

  2020cites this paper
• Cytochrome P450 Catalysis in the Biosynthesis of Natural Products

  2019cites this paper
• 10.03 – Mechanisms of Enzyme Catalysis and Inhibition☆

  2018cites this paper
• Squalene Cyclases and Cycloartenol Synthases from Polystichum polyblepharum and Six Allied Ferns

  2018cites this paper
• LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains

  2018cites this paper
• Pathway engineering for the production of β-amyrin and cycloartenol in Escherichia coli—a method to biosynthesize plant-derived triterpene skeletons in E. coli

  2017cites this paper
• Cloning and Expression Analysis of a Squalene Epoxidase Gene from Ginkgo biloba

  2017cites this paper
• Molecular Cloning and Expression of Squalene Epoxidase from a Medicinal Plant, Bupleurum chinense

  2016cites this paper
• Migrated Hopene Synthases from Colysis pothifolia and Identification of a Migration Switch Controlling the Number of 1,2‐Hydride and Methyl Shifts

  2016cites this paper
• Heterologous biosynthesis of triterpenoid dammarenediol-II in engineered Escherichia coli

  2016cites this paper
• Analysis of sterol metabolism in the pathogenic oomycetes Saprolegnia parasitica and Phytophthora infestans

  2016cites this paper
• CLONING AND CHARACTERIZATION OF THREE SQUALENE EPOXIDASE GENES IN PANAX VIETNAMENSIS VAR. FUSCIDICUS, A RARE MEDICINAL PLANT WITH HIGH CONTENT OF OCOTILLOL-TYPE GINSENOSIDES

  2016cites this paper
• The Regulatory Domain of Squalene Monooxygenase Contains a Re-entrant Loop and Senses Cholesterol via a Conformational Change*

  2015cites this paper
• Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure—a FRET study

  2015cites this paper
• Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis*

  2015cites this paper
• Isolation and Characterization of Two Squalene Epoxidase Genes from Botryococcus braunii, Race B

  2015cites this paper
• Flavin dependent monooxygenases.

  2014cites this paper
• Lipidomics for Geochemistry

  2014cites this paper
• Analyses of metabolic pathways of cellular processes in apoptosis and adipogenesis

  2013cites this paper
• Conformational Isomers of Calcineurin Follow Distinct Dissociation Pathways

  2012cites this paper
• Mechanisms of Cytochrome P450‐Mediated Reactions

  2012cites this paper
• Squalene monooxygenase – a target for hypercholesterolemic therapy

  2011cites this paper
• Detailed Mechanism of Squalene Epoxidase Inhibition by Terbinafine

  2011cites this paper
• Mechanism of Resistance to Dietary Cholesterol

  2011cites this paper
• Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epoxidase gene in Panax ginseng.

  2010cites this paper
• Perspectives of the non-statin hypolipidemic agents.

  2010cites this paper
• Molecular Evolution of Fern Squalene Cyclases

  2010cites this paper
• Mechanisms of Enzyme Catalysis and Inhibition

  2010cites this paper
• Molecular cloning and characterization of the gene encoding squalene epoxidase in Panax notoginseng

  2008cites this paper
• Antifungal Resistance Mechanisms in Dermatophytes

  2008cites this paper
• Squalene cyclase and oxidosqualene cyclase from a fern

  2008cites this paper
• Site-directed mutagenesis of conserved aromatic residues in rat squalene epoxidase.

  2007cites this paper
• A squalene epoxidase is involved in biosynthesis of both the antitumor compound clavaric acid and sterols in the basidiomycete H. sublateritium.

  2007cites this paper
• Arabidopsis thaliana Squalene Epoxidase 1 Is Essential for Root and Seed Development*

  2007cites this paper
• Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase.

  2007cites this paper
• Significance of cagA status and vacA subtypes of Helicobacter pylori in determining gastric histopathology: Virulence markers of H. pylori and histopathology

  2006cites this paper
• Cloning and characterization of the erg1 gene of Trichoderma harzianum: effect of the erg1 silencing on ergosterol biosynthesis and resistance to terbinafine.

  2006cites this paper
• 17Beta-hydroxysteroid dehydrogenase type 7 (Hsd17b7) reverts cholesterol auxotrophy in NS0 cells.

  2006cites this paper
• Vacuolar adenosine triphosphatase and pancreatic acinar cell function

  2006cites this paper
• Biosynthesis of the terpene phenalinolactone in Streptomyces sp. Tü6071: analysis of the gene cluster and generation of derivatives.

  2006cites this paper
• Glucagon‐like peptide 1(GLP‐1) in biology and pathology

  2005cites this paper
• Site-specific detection of S-nitrosylated PKB alpha/Akt1 from rat soleus muscle using CapLC-Q-TOF(micro) mass spectrometry.

  2005cites this paper
• Cytochrome P450 17alpha hydroxylase/17,20 lyase (CYP17) function in cholesterol biosynthesis: identification of squalene monooxygenase (epoxidase) activity associated with CYP17 in Leydig cells.

  2005cites this paper
• A channel in a transporter

  2005cites this paper
• Cytochrome P 450 17 Hydroxylase / 17 , 20 Lyase ( CYP 17 ) Function in Cholesterol Biosynthesis : Identification of Squalene Monooxygenase ( Epoxidase ) Activity Associated with CYP 17 in Leydig Cells

  2005cites this paper
• In situ study of K+ transport into the vacuole of Saccharomyces cerevisiae

  2005cites this paper
• Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia

  2005cites this paper
• Duplex RNA‐Binding Enzymes: Headliners from Neurobiology, Virology, and Development

  2005cites this paper
• Amino Acid Substitution in Trichophyton rubrum Squalene Epoxidase Associated with Resistance to Terbinafine

  2005cites this paper
• Imidazolinone-tolerant crops: history, current status and future.

  2005cites this paper
• Genetic and phenotype changes following in vitro interactions between Helicobacter pylori strains

  2004cites this paper
• SUPERNATANT PROTEIN FACTOR: INSIGHTS INTO ITS REGULATION AND ABILITY TO STIMULATE CHOLESTEROL SYNTHESIS IN VITRO AND IN CELL CULTURE

  2004cites this paper
• Photoaffinity labeling identifies the substrate-binding site of mammalian squalene epoxidase.

  2004cites this paper
• Key Players Involved in Bacterial Disulfide‐Bond Formation

  2004cites this paper
• Sequential treatment for Helicobacter pylori does not share the risk factors of triple therapy failure

  2004cites this paper
• Cancer Chemopreventive Activity of Monoterpenes and Other Isoprenoids

  2004cites this paper
• Pyridylamino‐β‐cyclodextrin as a Molecular Chaperone for Lipopolysaccharide Embedded in a Multilayered Polyelectrolyte Architecture

  2004cites this paper
• Stable isotope labeling for matrix-assisted laser desorption/ionization mass spectrometry and post-source decay analysis of ribonucleic acids.

  2003cites this paper
• Sulfonylurea herbicide-resistant Monochoria vaginalis in Korean rice culture.

  2003cites this paper
• The chemistry of the opioid receptor binding sites

  2003cites this paper
• Helicobacter pylori: resurrection of the cancer link

  2003cites this paper
• Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression

  2003cites this paper
• Hydrochlorothiazide abolishes the anti‐atherosclerotic effect of quinapril

  2003cites this paper
• Helicobacter pylori strains and histologically‐related lesions affect the outcome of triple eradication therapy: a study from southern Italy

  2003cites this paper
• Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidation and related reactions.

  2003cites this paper
• Saccharomyces cerevisiae Resistance in Molecular Mechanism of Terbinafine

  2003cites this paper
• Squalene epoxidase as hypocholesterolemic drug target revisited.

  2003cites this paper
• Decomposition of protein nitrosothiolsin matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry.

  2003cites this paper
• Molecular Mechanism of Terbinafine Resistance in Saccharomyces cerevisiae

  2003cites this paper
• Sterol Metabolism

  2002influential citation
• A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula.

  2002cites this paper
• Synthesis of fragments of the glycocalyx glycan of the parasite Schistosoma mansoni.

  2002cites this paper
• Ion channel formation and membrane‐linked pathologies of misfolded hydrophobic proteins: The role of dangerous unchaperoned molecules

  2002cites this paper
• Listeria monocytogenes mediated CFTR transgene transfer to mammalian cells

  2002cites this paper
• The first step of oxygenation in cholesterol biosynthesis.

  2002cites this paper
• SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase.

  2002cites this paper
• Relevance of VacA and Mucosal Pathological Changes among Chinese Patients with Upper Gastrointestinal Diseases after Helicobacter pylori Eradication

  2002cites this paper
• QTL analysis and localization of genes involved in the variation of cholesterol levels in the rat

  2002cites this paper
• Animal Cytogenetics and Comparative Mapping

  2002cites this paper
• Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls.

  2001cites this paper
• Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity.

  2001cites this paper
• Potent and selective inhibition of squalene epoxidase by synthetic galloyl esters.

  2000cites this paper
• Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase.

  2000cites this paper
• Galloyl Esters from Rhubarb are Potent Inhibitors of Squalene Epoxidase, a Key Enzyme in Cholesterol Biosynthesis

  2000cites this paper
• Photoaffinity labeling and site-directed mutagenesis of rat squalene epoxidase.

  2000cites this paper
• Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis.

  2000cites this paper
• Green tea polyphenols: novel and potent inhibitors of squalene epoxidase.

  2000cites this paper
• Biochemistry and Molecular Biology of the Xanthophyll Cycle

  1999cites this paper
• 3.02 – Glycosidases of the Asparagine-linked Oligosaccharide Processing Pathway

  1999cites this paper
• An example of intron junctional sliding in the gene families encoding squalene monooxygenase homologues in Arabidopsis thaliana and Brassica napus*

  1999cites this paper
• Biosynthèse des isoprénoïdes

  1999cites this paper
• 2.10 – Squalene Epoxidase and Oxidosqualene : Lanosterol Cyclase—Key Enzymes in Cholesterol Biosynthesis

  1999cites this paper
• 5.05 – Deamination of Nucleosides and Nucleotides and Related Reactions

  1999cites this paper
• Structure, Function, and Engineering of Bacterial Aromatic Polyketide Synthases

  1999cites this paper