SQLE
Domain
The C-terminal hydrophobic region contains two helices that mediate interaction with membranes. Contrary to predictions, this region does not contain transmembrane helices.
The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high (PubMed:24449766, PubMed:26434806, PubMed:28972164). The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices (PubMed:26434806). The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions (PubMed:28972164).
Function
Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
Pathway
Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 2/3.
Post-translational modifications
Ubiquitinated by MARCHF6 in response to high cholesterol levels in intracellular membranes, leading to proteasomal degradation.
Sequence Similarities
Belongs to the squalene monooxygenase family.
Tissue Specificity
Detected in liver (at protein level).
Cellular localization
- Microsome membrane
- Peripheral membrane protein
- Endoplasmic reticulum membrane
- Peripheral membrane protein
Alternative names
ERG1, SQLE, Squalene monooxygenase, Squalene epoxidase, SE