GO_REF:0000002

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000024

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000033

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000107

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000117

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000120

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

GO_REF:0000121

GO reference used by source annotation pipeline

Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.

"GO_REF entry used to trace source annotation method rather than as primary biological evidence."

PMID:11520216

Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase.

This paper tests ellagitannins and HHDP esters as recombinant rat squalene epoxidase inhibitors; it does not study biphenyl response.

"Ellagitannins isolated from various plant sources as well as newly synthesized n-alkyl (C(1)-C(18)) esters of hexahydroxydiphenyl (HHDP) dicarboxylic acid were evaluated as enzyme inhibitors of recombinant rat squalene epoxidase, a rate-limiting enzyme of cholesterol biosynthesis."

PMID:17112472

Site-directed mutagenesis of conserved aromatic residues in rat squalene epoxidase.

Rat squalene epoxidase mutagenesis supports squalene monooxygenase activity.

"Site-directed mutagenesis of conserved aromatic residues in rat squalene epoxidase."

PMID:7814369

Molecular cloning and expression of rat squalene epoxidase.

Rat Sqle cDNA expression supports functional squalene epoxidase activity and sterol biosynthesis role.

"Molecular cloning and expression of rat squalene epoxidase."

PMID:9300786

Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts.

Squalene epoxidase inhibition is used to perturb cholesterol biosynthesis in L6 myoblasts.

"Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts."

file:rat/Sqle/Sqle-deep-research-falcon.md

Falcon deep research on rat Sqle (Edison Scientific Literature)

SQLE catalyzes the stereospecific epoxidation of squalene to 2,3(S)-oxidosqualene, the first oxygenation step of the sterol branch of the mevalonate-cholesterol pathway, corroborating the squalene monooxygenase activity (GO:0004506) annotation.

"SQLE catalyzes the **stereospecific epoxidation** of **squalene** to **2,3(S)-oxidosqualene** (also termed 2,3-epoxysqualene), which is the **first oxygenation step** and a committed transformation within the sterol branch of the mevalonate–cholesterol pathway."
SQLE is an FAD-dependent monooxygenase, supporting the FAD/flavin adenine dinucleotide binding annotations as cofactor context.

"**Cofactor:** SQLE is **FAD-dependent**; crystal structures of the human catalytic domain show SQLE bound to **FAD**."
SQLE is an endoplasmic reticulum membrane-associated protein, supporting the ER/ER membrane localization annotations.

"SQLE is an **endoplasmic reticulum (ER) membrane-associated** protein. A regulatory **N-terminal ~100 aa (N100)** region mediates lipid sensing and degradation, while the **catalytic domain** spans the C-terminus (approximately aa 101–574 in human; highly conserved across mammals)."
SQLE acts after squalene synthase and before oxidosqualene cyclase in the mevalonate-cholesterol pathway, controlling flux into sterol production; this supports the general sterol/cholesterol biosynthetic process annotations, the replacement of the obsolete desmosterol/lathosterol branch terms, and the non-core treatment of the zymosterol term.

"SQLE functions in the **mevalonate-cholesterol pathway** after squalene synthase and before oxidosqualene cyclase, controlling flux into sterol production. Because it is one of the principal regulated steps in cholesterol synthesis, altered SQLE activity changes levels of cholesterol, squalene, and related metabolites such as CoQ pathway outputs indirectly via pathway flux redistribution."
SQLE receives electrons mainly via NADPH-cytochrome P450 reductase (POR/CPR) on the ER membrane, consistent with the catalytic activity using a reduced NADPH-hemoprotein reductase as electron donor.

"The principal electron donation route is **NADPH → NADPH–cytochrome P450 reductase (POR/CPR/P450R) → SQLE**."
Proliferation/cancer phenotypes attributed to SQLE arise from downstream cholesterol-dependent cellular states and recent tumor-immunity studies, not a direct SQLE molecular function; this supports marking regulation of cell population proliferation as over-annotated.

"making SQLE a metabolic “valve” controlling sterol pathway flux and altering levels of squalene and downstream cholesterol-dependent cellular states. Recent 2023–2024 studies extend SQLE’s relevance to ferroptosis modulation and tumor immunity, with pharmacologic inhibition (notably terbinafine) being evaluated in vivo for cancer-immunity contexts."