CYP8B1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008397 sterol 12-alpha-hydroxylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (PAN-GO/IBA) transfer of the defining molecular function. This is the correct, specific core activity of CYP8B1 (EC 1.14.14.139), consistent with the multiple experimental IDA annotations below. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Sterol 12-alpha-hydroxylase involved in primary bile acid
GO:0004497 monooxygenase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Correct but a general parent of the specific sterol 12-alpha-hydroxylase activity (GO:0008397, which is_a GO:0004497). CYP8B1 does act as a monooxygenase, but the more informative child term is preferred as the core function. Keep as an over-annotation rather than remove. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Functions as a monooxygenase, inserting one atom
GO:0005506 iron ion binding	IEA GO_REF:0000002	ACCEPT	Summary: Intrinsic to the cytochrome P450 heme-thiolate center; the catalytic heme iron is coordinated by a conserved axial cysteine. Well-supported InterPro IEA for a P450. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt axial binding residue
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct subcellular location. CYP8B1 is an ER-membrane, single-pass microsomal P450, consistent with UniProt subcellular location and Reactome. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Endoplasmic reticulum membrane
GO:0006629 lipid metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Correct but very general (ARBA IEA). CYP8B1 acts in bile-acid biosynthesis, a specific branch of lipid metabolism; the specific term GO:0006699 is preferred. Over-annotation. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Lipid metabolism; bile acid biosynthesis.
GO:0008397 sterol 12-alpha-hydroxylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (multi-method IEA, via EC 1.14.14.139 / RHEA and rat ortholog) assignment of the correct core molecular function. Redundant with the experimental IDA annotations; accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt 12alpha-hydroxylation of key
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Correct but a general parent (GO:0008397 is_a GO:0016705). Describes the generic P450 chemistry; the specific sterol 12-alpha-hydroxylase term is preferred as core. Over-annotation. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt of molecular oxygen into substrates while reducing the second to water,
GO:0020037 heme binding	IEA GO_REF:0000002	ACCEPT	Summary: Correct. Heme is the obligate cofactor of this cytochrome P450 (ChEBI:30413), and substrate titration produces the characteristic type I heme Soret shift. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Name=heme; PMID:39214664 Soret peak (type I binding).
GO:0072330 monocarboxylic acid biosynthetic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Correct but general (ARBA IEA). Bile acids are monocarboxylic acids, so this is a true parent of bile acid biosynthetic process (GO:0006699). The specific term is preferred. Over-annotation.
GO:0031667 response to nutrient levels	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl electronic transfer from the rat ortholog. Plausible on biological grounds - CYP8B1 mRNA is potently induced by starvation in mouse - but this is a regulatory/physiological response, not CYP8B1's core molecular activity. Keep as non-core. Supporting Evidence: PMID:10051404 potent induction of CYP8B1 mRNA was observed upon
GO:0070723 response to cholesterol	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl electronic transfer from the rat ortholog. Biologically plausible given cholesterol / bile-acid feedback regulation of the pathway, but not directly evidenced for the human enzyme and not a core molecular function. Keep as non-core.
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193368	ACCEPT	Summary: Correct core biological process (Reactome bile-salt synthesis via 7-alpha-hydroxycholesterol, the classic pathway in which CYP8B1 is the 12-alpha-hydroxylation branch step). Accept.
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193775	ACCEPT	Summary: Correct core biological process (Reactome bile-salt synthesis pathway). Redundant with the other bile-acid biosynthesis annotations. Accept.
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193807	ACCEPT	Summary: Correct core biological process (Reactome bile-salt synthesis pathway). Redundant Reactome TAS for bile-acid biosynthesis. Accept.
GO:0016125 sterol metabolic process	TAS Reactome:R-HSA-211994	KEEP AS NON CORE	Summary: Correct but general. CYP8B1 acts on sterol intermediates, but its role is best captured by the specific bile acid biosynthetic process (GO:0006699) plus the sterol 12-alpha-hydroxylase MF. Keep as non-core context.
GO:0006699 bile acid biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway mapping (bile acid biosynthesis, UPA00221) IEA to the correct core process. Redundant with experimental and TAS annotations. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Lipid metabolism; bile acid biosynthesis.
GO:0008397 sterol 12-alpha-hydroxylase activity	TAS Reactome:R-HSA-192157	ACCEPT	Summary: Reactome TAS for the defining reaction (CYP8B1 12-hydroxylates 7-alpha-hydroxycholest-4-en-3-one). Correct core molecular function. Accept.
GO:0008397 sterol 12-alpha-hydroxylase activity	TAS Reactome:R-HSA-193709	ACCEPT	Summary: Reactome TAS for the sterol 12-alpha-hydroxylase reaction. Correct core molecular function; redundant Reactome support. Accept.
GO:0008397 sterol 12-alpha-hydroxylase activity	TAS Reactome:R-HSA-193845	ACCEPT	Summary: Reactome TAS for the defining reaction (CYP8B1 12-hydroxylates 7-alpha,27-dihydroxy intermediate). Correct core molecular function. Accept.
GO:0006699 bile acid biosynthetic process	IDA PMID:30465713 Conversion of chenodeoxycholic acid to cholic acid by human ...	ACCEPT	Summary: Experimental (IDA): human CYP8B1 converts chenodeoxycholate to cholate and the C4 precursor to the cholic-acid intermediate, directly demonstrating its role in bile-acid biosynthesis. Accept as a core process. Supporting Evidence: PMID:30465713 CDCA precursor, to 7α,12α-dihydroxycholest-4-en-3-one, which is an intermediate
GO:0006699 bile acid biosynthetic process	IDA PMID:39214664 CYP8B1 Catalyzes 12alpha-Hydroxylation of C(27) Bile Acid: I...	ACCEPT	Summary: Experimental (IDA): recombinant and microsomal CYP8B1 12-alpha-hydroxylate C27 bile-acid intermediates (DHCA to THCA) and C4, mapping the enzyme onto the classic bile-acid synthesis pathway. Accept as a core process. Supporting Evidence: PMID:39214664 both microsomal and recombinant CYP8B1 enzymes catalyze the 12α-hydroxylation of
GO:0008397 sterol 12-alpha-hydroxylase activity	IDA PMID:30465713 Conversion of chenodeoxycholic acid to cholic acid by human ...	ACCEPT	Summary: Experimental (IDA) for the defining molecular function: recombinant human CYP8B1 catalyzes 12-alpha-hydroxylation, converting CDCA to cholic acid. Core function. Accept. Supporting Evidence: PMID:30465713 In this study we demonstrate that CYP8B1 can also convert
GO:0008397 sterol 12-alpha-hydroxylase activity	IDA PMID:39214664 CYP8B1 Catalyzes 12alpha-Hydroxylation of C(27) Bile Acid: I...	ACCEPT	Summary: Experimental (IDA) for the defining molecular function, with reaction phenotyping excluding other P450s: purified CYP8B1 12-alpha-hydroxylates C4 and DHCA with measured kinetics. Core function. Accept. Supporting Evidence: PMID:39214664 Sterol 12α-hydroxylase (CYP8B1) is the unique P450 enzyme with sterol
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from rabbit ortholog O02766) of the ER-membrane location. Correct and consistent with the single-pass microsomal P450 architecture. Accept. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Endoplasmic reticulum membrane
GO:0006699 bile acid biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the core biological process. Correct and redundant with the experimental IDA annotations. Accept.
GO:0008397 sterol 12-alpha-hydroxylase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from rabbit ortholog O02766) of the core molecular function. Correct and redundant with the experimental IDA annotations. Accept.
GO:0045797 positive regulation of intestinal cholesterol absorption	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from the mouse ortholog (O88962). CYP8B1 shapes the bile-acid pool (cholic vs chenodeoxycholic acid), which in turn drives intestinal absorption of dietary lipids and cholesterol; UniProt records this downstream physiological consequence. This is a downstream effect of the enzyme's activity rather than its core molecular function. Keep as non-core. Supporting Evidence: file:human/CYP8B1/CYP8B1-uniprot.txt Controls biliary balance of cholic acid and
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-192157	ACCEPT	Summary: Reactome TAS placing CYP8B1 activity at the ER membrane. Correct location; redundant with ISS/IEA. Accept.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-193709	ACCEPT	Summary: Reactome TAS for the ER-membrane location. Correct; redundant Reactome support. Accept.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-193845	ACCEPT	Summary: Reactome TAS for the ER-membrane location. Correct; redundant Reactome support. Accept.
GO:0019825 oxygen binding	TAS PMID:10051404 Structure and chromosomal assignment of the sterol 12alpha-h...	MARK AS OVER ANNOTATED	Summary: Legacy TAS/ProtInc annotation. Molecular O2 is a co-substrate of the P450 monooxygenase reaction, but "oxygen binding" (a carrier-type MF, e.g. hemoglobin) is not an informative description of this enzyme's function, and the cited paper (a gene-structure/cloning study) does not report O2-binding assays. The catalytic chemistry is captured by the monooxygenase / sterol 12-alpha-hydroxylase terms. Over-annotation; do not remove a TAS.
GO:0008397 sterol 12-alpha-hydroxylase activity	TAS PMID:10051404 Structure and chromosomal assignment of the sterol 12alpha-h...	ACCEPT	Summary: Author-traceable (TAS) assignment of the core molecular function from the original human CYP8B1 cloning study, which detected 12-alpha-hydroxylase enzymatic activity on expression in COS cells. Correct core function. Accept. Supporting Evidence: PMID:10051404 enzymatic activity for the

Gene Description

Existing Annotations Review

Core Functions

Heme binding: CYP8B1 binds heme (ChEBI:30413) as its obligate prosthetic group, coordinating the catalytic iron through a conserved axial cysteine; substrate binding produces the characteristic type I Soret shift of the ferric heme.

References

📚 Additional Documentation

Notes

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