Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain.
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Expression cloning of human and murine cholesterol 24-hydroxylase (CYP46); the enzyme converts cholesterol to 24S-hydroxycholesterol, localizes to the ER, and is expressed predominantly in brain neurons.
"the cDNAs produce an enzymatic activity that converts cholesterol into 24S-hydroxycholesterol"
Metabolism of 4 beta-hydroxycholesterol in humans.
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Primarily characterizes turnover of CYP3A4-derived 4beta-hydroxycholesterol; the CYP46A1 4beta-hydroxycholesterol 24S-hydroxylation activity is captured in the UniProt catalytic-activity block (RHEA:46392).
"One of the major oxysterols in the human circulation is 4 beta-hydroxycholesterol"
Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
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Recombinant CYP46A1 24(S)-hydroxylates cholesterol (the first step in brain cholesterol degradation) and has broad in vitro specificity, also hydroxylating C27 sterols, C21 steroid hormones (progesterone, testosterone), and xenobiotics.
"The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol"
Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain.
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Crystal structures of CYP46A1 (substrate-free and bound to cholesterol 3-sulfate) confirm the heme cofactor and productive substrate orientation for 24-hydroxylation; CYP46A1 initiates the major pathway for brain cholesterol removal.
"cytochrome P450 46A1 (CYP46A1) initiates the major pathway for cholesterol removal from the brain"
Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain.
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Crystal structures of CYP46A1 with four drugs show nitrogen ligands coordinating the heme iron; clotrimazole is also a CYP46A1 substrate. The enzyme controls brain cholesterol turnover and its loss impairs hippocampal plasticity/learning in mice.
"clotrimazole is also a substrate for CYP46A1"
Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response.
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Crystal structure of CYP46A1 with bicalutamide; a water molecule coordinated to the heme iron produces unusual spectral responses, confirming heme binding.
"a water molecule that is coordinated to the P450"
Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1.
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CYP46A1 oxidizes cholesterol to 24S-hydroxycholesterol and also oxidizes the cholesterol precursors 7-dehydrocholesterol and desmosterol, with potential relevance to Smith-Lemli-Opitz syndrome and desmosterolosis.
"its ability to oxidize cholesterol to 24S-hydroxycholesterol"
CYP46A1 24-hydroxylates CHOL
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Reactome reaction: CYP46A1, an ER-membrane enzyme expressed predominantly in brain, catalyzes 24-hydroxylation of cholesterol to 24-hydroxycholesterol.
"catalyses the 24-hydroxylation of cholesterol (CHOL) to 24-hydroxycholesterol"
Synthesis of bile acids and bile salts via 24-hydroxycholesterol
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24-hydroxycholesterol made in the brain is exported to the liver and converted to bile acids/salts, a minor but important route for disposing of excess brain cholesterol.
"24-hydroxycholesterol is synthesized in the brain, exported to the liver, and converted there to bile acids and bile salts"