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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A).
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Recombinant human CYP7A shows 7-alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol, with a preference for the (24S)-isomer, establishing CYP7A1 as a cholesterol/oxysterol 7-alpha-hydroxylase and the rate-limiting enzyme of bile acid biosynthesis.
"Human CYP7A, recombinantly expressed in Escherichia coli and in simian COS cells, showed 7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol"
Metabolism of 4 beta -hydroxycholesterol in humans.
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Recombinant human CYP7A1 7-alpha-hydroxylates 4-beta-hydroxycholesterol, albeit more slowly than cholesterol, confirming direct sterol 7-alpha-hydroxylase activity of the human enzyme.
"beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1"
Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.
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High glucose induces CYP7A1 mRNA and stimulates bile-acid synthesis in human hepatocytes; CYP7A1 is described as the key regulatory gene in bile acid synthesis, induced via an HNF4alpha-dependent, AMPK-modulated, epigenetic mechanism.
"High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol ... 7alpha-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis"
Molecular cloning and sequence analysis of cDNA encoding human cholesterol 7 alpha-hydroxylase.
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The human CYP7A1 cDNA encodes a 504-residue cholesterol 7-alpha-hydroxylase with conserved heme- and steroid-binding domains characteristic of steroidogenic cytochrome P450s.
"A complete cDNA clone encoding human cholesterol 7 ... alpha-hydroxylase has been isolated ... Unique amino acid residues were observed in putative binding domains for heme and steroid which are highly conserved in most steroidogenic P-450s"
CYP7A1 7-hydroxylates CHOL
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CYP7A1 catalyses cholesterol + NADPH + H+ + O2 to 7alpha-cholesterol + NADP+ + H2O in the endoplasmic reticulum membrane; the enzyme is expressed only in liver and is transcriptionally regulated to set the overall rate of bile acid/bile salt production.
"reaction catalysed by CYP7A1 (cholesterol 7alpha-hydroylase) in the endoplasmic reticulum membrane"
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
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The classic (neutral) hepatic bile-acid biosynthesis pathway is initiated by conversion of cholesterol to 7alpha-hydroxycholesterol (the CYP7A1 step).
"synthesis of bile acids and bile salts is initiated with the conversion of cholesterol to 7alpha-hydroxycholesterol"
Expression of CYP7A1
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Reactome event representing transcription/translation of the CYP7A1 gene; relevant to the transcriptional-regulation biology but not to the enzyme's molecular localization.
"The CYP7A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein"
Endogenous sterols
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A number of cytochrome P450s (including CYP7A1) participate in cholesterol elimination and homeostasis, degrading cholesterol to bile salts.
"A number of CYPs take part in cholesterol biosynthesis and elimination, thus playing an important role in maintaining cholesterol homeostasis"
UniProtKB P22680 (CP7A1_HUMAN) curated entry
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CYP7A1 is a cytochrome P450 monooxygenase that catalyses 7-alpha hydroxylation of cholesterol, the rate-limiting step in cholesterol catabolism and bile acid biosynthesis, and is a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis.
"Functions as a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis. Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis"
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The enzyme is localized to the endoplasmic reticulum (microsome) membrane as a single-pass membrane protein and uses heme as cofactor.
"SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"