Sqle

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004506 squalene monooxygenase activity	IBA GO_REF:0000033	ACCEPT	Summary: squalene monooxygenase activity is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. file:rat/Sqle/Sqle-deep-research-falcon.md 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.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Endoplasmic reticulum localization of Sqle, inferred phylogenetically from a PAINT node (PANTHER:PTN000089417) seeded by yeast ERG1, mouse Sqle, human SQLE and other experimentally localized squalene epoxidases. Reason: Squalene epoxidase is an ER enzyme throughout eukaryotes, and rat Sqle lies inside the vertebrate clade with no evidence of divergence, so the node placement is sound. The ER is where squalene epoxidation takes place, so this is accepted as the core location (earlier reviews kept it as non-core). Supporting Evidence: UniProtKB:P52020 Endoplasmic reticulum membrane; Peripheral membrane protein file:rat/Sqle/Sqle-deep-research-falcon.md SQLE is an endoplasmic reticulum (ER) membrane-associated protein.
GO:0004506 squalene monooxygenase activity	IEA GO_REF:0000120	ACCEPT	Summary: squalene monooxygenase activity is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Endoplasmic reticulum membrane localization of Sqle, from the combined UniProt/Ensembl orthology pipeline (human SQLE) and the UniProt subcellular location. Reason: Rat Sqle was characterized as a microsomal enzyme, and its mammalian orthologs are peripheral ER membrane proteins anchored by C-terminal amphipathic helices. The ER membrane is the compartment in which the core reaction occurs, so the term is accepted as core (earlier reviews kept it as non-core). Supporting Evidence: UniProtKB:P52020 SUBCELLULAR LOCATION: Microsome membrane UniProtKB:P52020 Endoplasmic reticulum membrane; Peripheral membrane protein
GO:0008203 cholesterol metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: cholesterol metabolic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000117). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. GOA no longer carries this electronic row (retired); the role is still captured by the cholesterol and sterol biosynthesis rows. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. file:rat/Sqle/Sqle-deep-research-falcon.md 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.
GO:0016020 membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Generic membrane localization of Sqle from the combined orthology/InterPro pipeline. Reason: Correct but uninformative: Sqle is a peripheral membrane protein of the ER, and the specific location is captured by the endoplasmic reticulum membrane rows. Kept as a non-core parent location. Supporting Evidence: UniProtKB:P52020 The C-terminal hydrophobic region contains two helices that mediate interaction with membranes.
GO:0016126 sterol biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: sterol biosynthetic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0050660 flavin adenine dinucleotide binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: FAD binding mapped from the squalene epoxidase/FAD-binding domain signature (InterPro:IPR013698). Reason: Squalene epoxidase is a flavoprotein that uses FAD as its cofactor, and the rat sequence carries the FAD-binding dinucleotide motif. FAD binding is a genuine but supporting property of the monooxygenase activity, so it is kept as non-core. Supporting Evidence: UniProtKB:P52020 Name=FAD; Xref=ChEBI:CHEBI:57692 PMID:7814369 This region also contains a beta 1-alpha A-beta 2 motif, which is the consensus sequence for an FAD binding domain, suggesting that SE is a flavoenzyme.
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: cholesterol biosynthetic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. GOA no longer carries this electronic row (retired); the same term remains supported by other rows. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. file:rat/Sqle/Sqle-deep-research-falcon.md 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.
GO:0033489 cholesterol biosynthetic process via desmosterol	IEA GO_REF:0000107	MODIFY	Summary: cholesterol biosynthetic process via desmosterol captures part of Sqle biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000107). Reason: Sqle acts at the common early squalene-to-epoxysqualene step, upstream of the point where the Bloch (desmosterol) and Kandutsch-Russell (lathosterol) routes diverge, so a branch-specific term is more specific than the evidence warrants. GO:0033489 and GO:0033490 are obsolete in the current QuickGO record (checked 2026-10-17; "represents a specific pathway variant, which is out of scope for GO") with replaced_by GO:0006695 cholesterol biosynthetic process, which is the replacement proposed here. This matches the treatment of the same rows in the Lss review. GOA no longer carries this row (retired), so the review is kept for provenance only. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. file:rat/Sqle/Sqle-deep-research-falcon.md SQLE functions in the mevalonate-cholesterol pathway after squalene synthase and before oxidosqualene cyclase, controlling flux into sterol production.
GO:0033490 cholesterol biosynthetic process via lathosterol	IEA GO_REF:0000107	MODIFY	Summary: cholesterol biosynthetic process via lathosterol captures part of Sqle biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000107). Reason: Sqle acts at the common early squalene-to-epoxysqualene step, upstream of the point where the Bloch (desmosterol) and Kandutsch-Russell (lathosterol) routes diverge, so a branch-specific term is more specific than the evidence warrants. GO:0033489 and GO:0033490 are obsolete in the current QuickGO record (checked 2026-10-17; "represents a specific pathway variant, which is out of scope for GO") with replaced_by GO:0006695 cholesterol biosynthetic process, which is the replacement proposed here. This matches the treatment of the same rows in the Lss review. GOA no longer carries this row (retired), so the review is kept for provenance only. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0036197 zymosterol biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Zymosterol biosynthetic process transferred electronically from mouse Sqle (UniProtKB:P52019). Reason: Squalene epoxidation is an upstream step on the route from squalene through lanosterol to zymosterol, so Sqle does catalyze a step of zymosterol formation. The term names an intermediate end-point rather than the physiological product, and the cholesterol and sterol biosynthesis rows already capture the core role, so it is kept as non-core (earlier reviews proposed MODIFY to cholesterol biosynthetic process, which the gene already carries). Supporting Evidence: UniProtKB:P52020 Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 2/3.
GO:0042127 regulation of cell population proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: regulation of cell population proliferation is marked as over-annotated for Sqle; the evidence supports the gene's core activity or context, not this broader process claim (IEA, GO_REF:0000107). Reason: The available support is for squalene monooxygenase activity and sterol biosynthesis; this term appears to reflect downstream cholesterol-dependent cellular consequences or perturbation response rather than a direct Sqle function. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. file:rat/Sqle/Sqle-deep-research-falcon.md 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.
GO:0071949 FAD binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: FAD binding transferred electronically from human SQLE (UniProtKB:Q14534). Reason: FAD is the cofactor of squalene epoxidase in both human and rat. Genuine but supporting to the catalytic activity, so kept as non-core. Supporting Evidence: UniProtKB:P52020 Name=FAD; Xref=ChEBI:CHEBI:57692
GO:0098554 cytoplasmic side of endoplasmic reticulum membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cytoplasmic side of the ER membrane, transferred electronically from mouse Sqle (UniProtKB:P52019). Reason: Sqle is a peripheral membrane protein attached to the ER by C-terminal helices, with its catalytic domain facing the cytosol, so the cytoplasmic face is consistent with its topology. The term refines the core ER-membrane location and is kept as non-core. Supporting Evidence: UniProtKB:P52020 Endoplasmic reticulum membrane; Peripheral membrane protein
GO:0140042 lipid droplet formation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Lipid droplet formation transferred electronically from human SQLE (UniProtKB:Q14534). Reason: The human annotation rests on the SQLE-SMIM22 interaction, which modulates lipid droplet formation. This is a regulatory, context-specific role and not the catalytic function, so it is kept as non-core. Supporting Evidence: UniProtKB:P52020 Interacts with SMIM22; this interaction modulates lipid droplet formation.
GO:0033490 cholesterol biosynthetic process via lathosterol	ISO GO_REF:0000121	MODIFY	Summary: cholesterol biosynthetic process via lathosterol captures part of Sqle biology, but a more specific or better-aspected GO term should replace it (ISO, GO_REF:0000121). Reason: Sqle acts at the common early squalene-to-epoxysqualene step, upstream of the point where the Bloch (desmosterol) and Kandutsch-Russell (lathosterol) routes diverge, so a branch-specific term is more specific than the evidence warrants. GO:0033489 and GO:0033490 are obsolete in the current QuickGO record (checked 2026-10-17; "represents a specific pathway variant, which is out of scope for GO") with replaced_by GO:0006695 cholesterol biosynthetic process, which is the replacement proposed here. This matches the treatment of the same rows in the Lss review. GOA no longer carries this row (retired), so the review is kept for provenance only. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:109296 · mouse Sqle SUPPORTS SOURCE BUT NOT TARGET Mouse Sqle donor supports squalene epoxidation at the common step upstream of the branch point; the lathosterol-route-specific term exceeds what the donor evidence shows. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0098554 cytoplasmic side of endoplasmic reticulum membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Cytoplasmic side of the ER membrane, transferred from mouse Sqle (MGI:MGI:109296). Reason: Consistent with Sqle being a peripheral ER membrane protein whose catalytic domain faces the cytosol. A refinement of the core ER-membrane location, kept as non-core. Supporting Evidence: UniProtKB:P52020 Endoplasmic reticulum membrane; Peripheral membrane protein
GO:0033489 cholesterol biosynthetic process via desmosterol	ISO GO_REF:0000121	MODIFY	Summary: cholesterol biosynthetic process via desmosterol captures part of Sqle biology, but a more specific or better-aspected GO term should replace it (ISO, GO_REF:0000121). Reason: Sqle acts at the common early squalene-to-epoxysqualene step, upstream of the point where the Bloch (desmosterol) and Kandutsch-Russell (lathosterol) routes diverge, so a branch-specific term is more specific than the evidence warrants. GO:0033489 and GO:0033490 are obsolete in the current QuickGO record (checked 2026-10-17; "represents a specific pathway variant, which is out of scope for GO") with replaced_by GO:0006695 cholesterol biosynthetic process, which is the replacement proposed here. This matches the treatment of the same rows in the Lss review. GOA no longer carries this row (retired), so the review is kept for provenance only. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:109296 · mouse Sqle SUPPORTS SOURCE BUT NOT TARGET Mouse Sqle donor supports squalene epoxidation at the common step upstream of the branch point; the desmosterol-route-specific term exceeds what the donor evidence shows. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0004506 squalene monooxygenase activity	ISO GO_REF:0000121	ACCEPT	Summary: squalene monooxygenase activity is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0036197 zymosterol biosynthetic process	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Zymosterol biosynthetic process transferred from mouse Sqle (MGI:MGI:109296). Reason: As for the IEA row: Sqle catalyzes an upstream step on the route to zymosterol, but the term names an intermediate end-point, so it is kept as non-core rather than replaced with cholesterol biosynthetic process, which the gene already carries. Supporting Evidence: UniProtKB:P52020 Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 2/3.
GO:0005789 endoplasmic reticulum membrane	ISO GO_REF:0000121	ACCEPT	Summary: Endoplasmic reticulum membrane localization transferred from human SQLE (UniProtKB:Q14534). Reason: Human SQLE is a peripheral ER membrane protein, and the rat enzyme is microsomal. The ER membrane is where the core reaction occurs, so the location is accepted as core (earlier reviews kept it as non-core). Supporting Evidence: UniProtKB:P52020 Endoplasmic reticulum membrane; Peripheral membrane protein
GO:0006695 cholesterol biosynthetic process	ISO GO_REF:0000121	ACCEPT	Summary: cholesterol biosynthetic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0004506 squalene monooxygenase activity	EXP PMID:17112472 Site-directed mutagenesis of conserved aromatic residues in ...	ACCEPT	Summary: squalene monooxygenase activity is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (EXP, PMID:17112472). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: PMID:17112472 Site-directed mutagenesis of conserved aromatic residues in rat squalene epoxidase. file:rat/Sqle/Sqle-deep-research-falcon.md 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.
GO:0042127 regulation of cell population proliferation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: regulation of cell population proliferation is marked as over-annotated for Sqle; the evidence supports the gene's core activity or context, not this broader process claim (ISS, GO_REF:0000024). Reason: The available support is for squalene monooxygenase activity and sterol biosynthesis; this term appears to reflect downstream cholesterol-dependent cellular consequences or perturbation response rather than a direct Sqle function. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0140042 lipid droplet formation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Lipid droplet formation inferred by sequence similarity to human SQLE (UniProtKB:Q14534). Reason: Based on the human SQLE-SMIM22 interaction that modulates lipid droplet formation. A context-specific regulatory role rather than the catalytic function; kept as non-core. Supporting Evidence: UniProtKB:P52020 Interacts with SMIM22; this interaction modulates lipid droplet formation.
GO:0042127 regulation of cell population proliferation	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: regulation of cell population proliferation is marked as over-annotated for Sqle; the evidence supports the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121). Reason: The available support is for squalene monooxygenase activity and sterol biosynthesis; this term appears to reflect downstream cholesterol-dependent cellular consequences or perturbation response rather than a direct Sqle function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:Q14534 · human SQLE SUPPORTS SOURCE BUT NOT TARGET Human SQLE donor evidence reflects proliferation phenotypes upon SQLE perturbation -- a downstream cholesterol-dependent effect, not a direct function transferable to rat. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0140042 lipid droplet formation	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Lipid droplet formation transferred from human SQLE (UniProtKB:Q14534) by orthology. Reason: Same basis as the ISS row: the SQLE-SMIM22 interaction modulates lipid droplet formation. Context-specific and not the catalytic function; kept as non-core. Supporting Evidence: UniProtKB:P52020 Interacts with SMIM22; this interaction modulates lipid droplet formation.
GO:0016020 membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Generic membrane localization inferred by sequence similarity to human SQLE (UniProtKB:Q14534). Reason: Correct but uninformative parent of the ER membrane location. Kept as non-core. Supporting Evidence: UniProtKB:P52020 The C-terminal hydrophobic region contains two helices that mediate interaction with membranes.
GO:0016126 sterol biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: sterol biosynthetic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (ISS, GO_REF:0000024). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0071949 FAD binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: FAD binding inferred by sequence similarity to human SQLE (UniProtKB:Q14534). Reason: FAD is the flavin cofactor of squalene epoxidase. Genuine but supporting to the catalytic activity, so kept as non-core. Supporting Evidence: UniProtKB:P52020 Name=FAD; Xref=ChEBI:CHEBI:57692
GO:0016020 membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Generic membrane localization transferred from human SQLE (UniProtKB:Q14534). Reason: Correct but uninformative parent of the ER membrane location. Kept as non-core. Supporting Evidence: UniProtKB:P52020 The C-terminal hydrophobic region contains two helices that mediate interaction with membranes.
GO:0016126 sterol biosynthetic process	ISO GO_REF:0000121	ACCEPT	Summary: sterol biosynthetic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
GO:0071949 FAD binding	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: FAD binding transferred from human SQLE (UniProtKB:Q14534) by orthology. Reason: FAD is the flavin cofactor of squalene epoxidase. Genuine but supporting to the catalytic activity, so kept as non-core. Supporting Evidence: UniProtKB:P52020 Name=FAD; Xref=ChEBI:CHEBI:57692
GO:0008203 cholesterol metabolic process	IMP PMID:9300786 Inhibition of cholesterol biosynthesis by squalene epoxidase...	ACCEPT	Summary: cholesterol metabolic process is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IMP, PMID:9300786). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: PMID:9300786 Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts.
GO:1904614 response to biphenyl	IDA PMID:11520216 Ellagitannins and hexahydroxydiphenoyl esters as inhibitors ...	REMOVE	Summary: Response to biphenyl, based on in vitro inhibition of recombinant rat squalene epoxidase by ellagitannins and hexahydroxydiphenyl (HHDP) esters. Reason: HHDP is a hexahydroxy-biphenyl dicarboxylic acid, so the annotation evidently records that biphenyl-containing compounds inhibit the enzyme. The paper measures IC50 values for inhibition of recombinant rat Sqle. Being inhibited by a compound in an enzyme assay is a property of the enzyme, not a cellular or organismal process that responds to a biphenyl stimulus, which is what GO:1904614 describes. Even if the full text has more inhibitor data, inhibition of Sqle would not make Sqle a participant in a response process. The term misrepresents the finding and is removed; the inhibition data themselves are not in question. (Earlier review text said the paper does not mention biphenyl; that was incorrect, since HHDP esters are biphenyl derivatives.) Supporting Evidence: PMID:11520216 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
GO:0004506 squalene monooxygenase activity	IDA PMID:7814369 Molecular cloning and expression of rat squalene epoxidase.	ACCEPT	Summary: squalene monooxygenase activity is retained for Sqle because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:7814369). Reason: The annotation is directly consistent with Sqle catalyzing squalene epoxidation in sterol/cholesterol biosynthesis. Supporting Evidence: PMID:7814369 Molecular cloning and expression of rat squalene epoxidase.
GO:0004506 squalene monooxygenase activity	ISO GO_REF:0000121	ACCEPT	Summary: Squalene monooxygenase activity transferred from human SQLE (UniProtKB:Q14534) by orthology; a donor-split duplicate of the ISO row from mouse Sqle. Reason: Human SQLE is the direct ortholog with well-characterized squalene epoxidase activity. The transfer agrees with direct evidence for the rat enzyme: recombinant rat Sqle is a functional squalene epoxidase. Supporting Evidence: UniProtKB:P52020 FUNCTION: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. PMID:7814369 Expression of a full-length rat SE protein in Escherichia coli confirms this polypeptide as a functional SE.
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Cholesterol biosynthetic process from the combined UniProt/Ensembl orthology pipeline (mouse Sqle and human SQLE). Reason: Sqle catalyzes the first oxygenation step of sterol synthesis, converting squalene to 2,3-epoxysqualene, the substrate of lanosterol synthase; it therefore performs a step of cholesterol biosynthesis. Supporting Evidence: PMID:17112472 Squalene epoxidase catalyzes the conversion of squalene to (3S)2,3-oxidosqualene, which is a rate-limiting step of the cholesterol biogenesis.
GO:0006695 cholesterol biosynthetic process	ISO GO_REF:0000121	ACCEPT	Summary: Cholesterol biosynthetic process transferred from human SQLE (UniProtKB:Q14534) by orthology; a donor-split duplicate of the ISO row from mouse Sqle. Reason: Human SQLE and rat Sqle catalyze the same rate-limiting epoxidation step in cholesterol synthesis, so the transfer is sound. Supporting Evidence: PMID:17112472 Squalene epoxidase catalyzes the conversion of squalene to (3S)2,3-oxidosqualene, which is a rate-limiting step of the cholesterol biogenesis.
GO:0016125 sterol metabolic process	IEA GO_REF:0000117	MODIFY	Summary: Sterol metabolic process assigned by an ARBA rule (ARBA:ARBA00034378). Reason: Correct but too general: Sqle acts only in the biosynthetic direction, catalyzing the first oxygenation step of sterol synthesis. Replace with sterol biosynthetic process, which the gene already carries from IBA, ISS, ISO and IEA evidence. Proposed replacements: sterol biosynthetic process Supporting Evidence: PMID:7814369 Squalene epoxidase (SE) (EC 1.14.99.7) catalyzes the first oxygenation step in sterol biosynthesis
GO:0016126 sterol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Sterol biosynthetic process inferred phylogenetically from PAINT node PANTHER:PTN000089417, grounded in experimental annotations of yeast ERG1, Arabidopsis, Candida, mouse and human squalene epoxidases. Reason: Squalene epoxidation is an ancestral eukaryotic sterol-pathway step, and rat Sqle lies inside the clade with no sign of divergence. Consistent with the direct rat evidence. Supporting Evidence: PMID:7814369 Squalene epoxidase (SE) (EC 1.14.99.7) catalyzes the first oxygenation step in sterol biosynthesis
GO:1902652 secondary alcohol metabolic process	IEA GO_REF:0000117	MODIFY	Summary: Secondary alcohol metabolic process assigned by an ARBA rule (ARBA:ARBA00034391). Reason: Technically true, because sterols such as cholesterol are secondary alcohols, but the term is a chemical-class grouping that carries little information about Sqle. Replace with cholesterol biosynthetic process, the specific pathway in which Sqle catalyzes a step. Proposed replacements: cholesterol biosynthetic process Supporting Evidence: PMID:17112472 Squalene epoxidase catalyzes the conversion of squalene to (3S)2,3-oxidosqualene, which is a rate-limiting step of the cholesterol biogenesis.

Gene Description

Existing Annotations Review

Core Functions

Sqle catalyzes the FAD-dependent epoxidation of squalene to (S)-2,3-epoxysqualene, an early committed reaction in sterol and cholesterol biosynthesis.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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