|Gene:||SQLE||Accession Number: HS02595 (MetaCyc)|
Synonyms: squalene epoxidase, squalene-2,3-epoxidase
Species: Homo sapiens
A human liver cDNA was isolated that contained an open reading frame of 574 amino acids, corresponding to a protein with a molecular mass of 63,927 Da. It was 84% identical to rat and mouse enzymes. It was identified as a flavoprotein monooxygenase [Laden00].
Comment from LocusLink [Pruitt01]: Squalene epoxidase; enzyme of the sterol biosynthetic pathway. Summary: Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway.
Locuslink ID: (6713). Locus confirmed. Locus status: REVIEWED. Locus evidence: supported by alignment with mRNA.
Locations: endoplasmic reticulum
|Map Position: [126,015,909 -> 126,039,003]|
|Biological Process:||GO:0022900 - electron transport chain|
|Cellular Component:||GO:0005783 - endoplasmic reticulum [Reinhart87]|
Enzymatic reaction of: squalene,NADPH:oxygen oxidoreductase (2,3-epoxidizing) (squalene monooxygenase)
EC Number: 188.8.131.52
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is physiologically favored in the direction shown.
In Pathways: superpathway of cholesterol biosynthesis , cholesterol biosynthesis I , cholesterol biosynthesis II (via 24,25-dihydrolanosterol) , cholesterol biosynthesis III (via desmosterol) , epoxysqualene biosynthesis
A truncated form of this enzyme lacking the first 110 amino acids was expressed in E. coli, purified and characterized. The Kcat for squalene was 1.1 pmol/min/pmol. The Km for FAD was 0.3 μM. IC50s for tellurite and selenite were 17 μM and 37 μM, respectively. The enzyme was dependent upon coupling with NADPH-cytochrome P450 reductase for reducing equivalents [Laden00].
Nagai02: Nagai M, Sakakibara J, Nakamura Y, Gejyo F, Ono T (2002). "SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase." Biochem Biophys Res Commun 295(1);74-80. PMID: 12083769
Nagai97: Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S, Arakawa M, Ono T (1997). "Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1." Genomics 44(1);141-3. PMID: 9286711
Nakamura96a: Nakamura Y, Sakakibara J, Izumi T, Shibata A, Ono T (1996). "Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells." J Biol Chem 271(14);8053-6. PMID: 8626488
Reinhart87: Reinhart MP, Billheimer JT, Faust JR, Gaylor JL (1987). "Subcellular localization of the enzymes of cholesterol biosynthesis and metabolism in rat liver." J Biol Chem 262(20);9649-55. PMID: 3597431
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