CYP11B1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006704 glucocorticoid biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to glucocorticoid biosynthesis. CYP11B1 catalyses the final, committed step of cortisol (the principal human glucocorticoid) synthesis, so this is a core biological process. Reason: Well supported: CYP11B1 hydroxylates 11-deoxycortisol to cortisol, the terminal step of glucocorticoid biosynthesis. Consistent with the UniProt PATHWAY assignment and the experimental cortisol-biosynthesis annotations below. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Steroid biosynthesis; glucocorticoid biosynthesis. PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol.
GO:0034650 cortisol metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic annotation to the broad cortisol metabolic process. CYP11B1 produces cortisol, so it participates in cortisol metabolism, but the more precise and experimentally supported term is the cortisol biosynthetic child term. Reason: Correct but less specific than GO:0034651 cortisol biosynthetic process (which is directly supported by IDA/IMP evidence). Retained as a non-core parent term to avoid redundancy with the specific biosynthetic annotation. Supporting Evidence: PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol.
GO:0004507 steroid 11-beta-monooxygenase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to the defining molecular function: steroid 11-beta-monooxygenase (EC 1.14.15.4). This is the core catalytic activity of CYP11B1. Reason: This is the correct, specific molecular function; it is independently supported by multiple experimental (IDA/IMP) annotations and by the UniProt catalytic-activity data. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt 11beta position, yielding cortisol or corticosterone, respectively, but
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation placing CYP11B1 activity at the mitochondrial inner membrane, matching the experimentally and homology-supported subcellular location. Reason: CYP11B1 is a mitochondrial inner-membrane peripheral membrane protein; this is the core cellular location where its catalysis occurs (with its adrenodoxin electron partners). Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0032342 aldosterone biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic annotation to aldosterone biosynthesis, propagated across the CYP11B family. Human CYP11B1 lacks efficient 18-oxidase activity and cannot produce aldosterone; aldosterone synthesis is the function of the paralog CYP11B2. Reason: Over-annotation from the CYP11B ancestral family. Human CYP11B1 substantially fails to form aldosterone; the aldosterone-synthase role belongs to CYP11B2. In some species, e.g. bovine, a single CYP11B combines both activities, which is why the phylogenetic transfer includes this term. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG PSEUDO OR SUBACTIVITY LOSS Sources checked: UniProtKB:P19099 · CYP11B2 (aldosterone synthase) SUPPORTS SOURCE BUT NOT TARGET Aldosterone synthesis is the function of the paralog CYP11B2; human CYP11B1 lacks efficient 18-oxidase activity and cannot complete aldosterone synthesis. MGI:MGI:88584 · Cyp11b2 SUPPORTS SOURCE BUT NOT TARGET Mouse aldosterone-synthase paralog; term does not transfer to human CYP11B1. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Due to its lack of 18-oxidation activity, it is incapable of generating PMID:2256920 P-450(11)beta substantially fails to catalyze the
GO:0071375 cellular response to peptide hormone stimulus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: CYP11B1 expression/activity in the adrenal cortex is induced by ACTH, a peptide hormone. This is a regulatory/physiological response context rather than the enzyme's core catalytic role. Reason: Biologically reasonable (ACTH is the principal trophic stimulus that drives CYP11B1 transcription and cortisol output) but peripheral to the core molecular function; retained as non-core. Supporting Evidence: PMID:19342457 NRSF/NRSE is also involved in angiotensin II- and K(+)-stimulated augmentation of CYP11B2 and CYP11B1 gene transcription
GO:0008203 cholesterol metabolic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic annotation to cholesterol metabolism, transferred from CYP11-family members (with/from includes CYP11A1-type sequences P00189/P05108). CYP11B1 acts on C21 steroid substrates (11-deoxycortisol, 11-deoxycorticosterone), not on cholesterol; cholesterol side-chain cleavage is performed by CYP11A1. Reason: Over-propagated within the CYP11 family. CYP11B1 does not metabolize cholesterol; its substrates are downstream C21 steroids. The cholesterol-metabolizing enzyme of the pathway is CYP11A1 (cholesterol side-chain cleavage). Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: UniProtKB:P05108 · CYP11A1 (cholesterol side-chain cleavage) SUPPORTS SOURCE BUT NOT TARGET Cholesterol metabolism belongs to CYP11A1; CYP11B1 acts on C21 steroids downstream, so the cholesterol term should not transfer. UniProtKB:P00189 · CYP11A1 (bovine) SUPPORTS SOURCE BUT NOT TARGET CYP11A1-type source in the with/from field; not a CYP11B1 activity. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt deoxycortisol and 11-deoxycorticosterone (21-hydroxyprogesterone) at
GO:0047783 corticosterone 18-monooxygenase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic annotation to 18-monooxygenase activity. CYP11B1 has weak residual 18-hydroxylase activity (it is described as a steroid 11beta-, 18- and 19-hydroxylase with preferred 11beta regioselectivity) but this is a minor side activity; the physiologically dominant 18-hydroxylase/oxidase is CYP11B2. Reason: Retained as a genuine but minor secondary activity. UniProt notes CYP11B1 acts as a steroid 11beta-, 18- and 19-hydroxylase (preferred at 11beta), but its lack of efficient 18-oxidation is why it cannot complete aldosterone synthesis. Not a core function. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Due to its lack of 18-oxidation activity, it is incapable of generating
GO:0004497 monooxygenase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation to the general monooxygenase activity, based on the cytochrome P450 domain signatures. Reason: Correct parent of the specific steroid 11-beta-monooxygenase activity; a valid, if broad, molecular-function annotation for a cytochrome P450. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt A cytochrome P450 monooxygenase mainly involved in the
GO:0004507 steroid 11-beta-monooxygenase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA/RHEA/EC 1.14.15.4) to the core steroid 11-beta-monooxygenase activity. Matches the experimentally supported molecular function. Reason: Correct and specific; consistent with UniProt catalytic activity and the experimental IDA/IMP annotations for this same term. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt 11beta position, yielding cortisol or corticosterone, respectively, but
GO:0005506 iron ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO annotation for iron ion binding, reflecting the catalytic heme iron of the cytochrome P450. Reason: Correct: CYP11B1 coordinates a heme iron (axial cysteine ligand at position 450) that is essential for oxygen activation. Iron binding is a valid molecular function for this heme-thiolate enzyme. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt axial binding residue
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to mitochondrion. Correct but less specific than the mitochondrial inner membrane location. Reason: Valid broad localization; the more precise term (mitochondrial inner membrane) is also annotated and is the core location. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (UniProt subcellular-location keyword mapping) to mitochondrial inner membrane, matching the curated location. Reason: Correct and specific; consistent with the experimental (IC/TAS) and ISS annotations for this location. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0016125 sterol metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation to sterol metabolic process. CYP11B1's substrates are C21 steroid hormones (11-deoxycortisol, 11-deoxycorticosterone) rather than sterols such as cholesterol; this is a broad and somewhat imprecise term for this enzyme. Reason: Steroids are formally sterol derivatives, so the term is not strictly wrong, but it is broad and not the enzyme's specific role. The precise processes (glucocorticoid/cortisol biosynthesis, C21-steroid hormone biosynthesis) are annotated separately. Retained as non-core. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt deoxycortisol and 11-deoxycorticosterone (21-hydroxyprogesterone) at
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO annotation to the oxidoreductase (paired-donor, O2-incorporating) class, the mechanistic parent of monooxygenase/P450 activity. Reason: Mechanistically correct: CYP11B1 inserts one oxygen atom into the substrate and reduces the other to water. A valid broad molecular-function annotation. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt A cytochrome P450 monooxygenase mainly involved in the
GO:0020037 heme binding	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to heme binding, reflecting the essential heme cofactor of this heme-thiolate cytochrome P450. Reason: Correct: CYP11B1 binds heme via an axial cysteine ligand (position 450); heme is required for catalysis. Core cofactor-binding function. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Name=heme;
GO:0032342 aldosterone biosynthetic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic annotation to aldosterone biosynthesis, likely propagated across the CYP11B family. Human CYP11B1 cannot generate aldosterone. Reason: Same over-annotation as the IBA aldosterone term: human CYP11B1 lacks 18-oxidase activity and does not make aldosterone; this is the function of CYP11B2. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Due to its lack of 18-oxidation activity, it is incapable of generating PMID:2256920 P-450(11)beta substantially fails to catalyze the
GO:0006704 glucocorticoid biosynthetic process	TAS Reactome:R-HSA-194002	ACCEPT	Summary: Reactome (TAS) annotation from the Glucocorticoid biosynthesis pathway, in which CYP11B1 converts 11-deoxycortisol to cortisol. Reason: Core biological process, curator-asserted from the Reactome pathway; consistent with the IBA and experimental cortisol-biosynthesis annotations. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Steroid biosynthesis; glucocorticoid biosynthesis.
GO:0016125 sterol metabolic process	TAS Reactome:R-HSA-211976	KEEP AS NON CORE	Summary: Reactome (TAS) annotation from the "Endogenous sterols" pathway, a broad grouping of CYP-mediated steroidogenic/sterol reactions. Reason: Broad parent term; CYP11B1's substrates are C21 steroids rather than sterols per se. Not wrong, but the specific glucocorticoid/C21-steroid biosynthetic terms capture the core role. Retained as non-core. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt deoxycortisol and 11-deoxycorticosterone (21-hydroxyprogesterone) at
GO:0006704 glucocorticoid biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway-based electronic annotation to glucocorticoid biosynthesis (UPA00788), matching the curated pathway assignment. Reason: Correct core biological process, consistent with the UniProt PATHWAY line and the experimental cortisol-biosynthesis annotations. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Steroid biosynthesis; glucocorticoid biosynthesis.
GO:0004507 steroid 11-beta-monooxygenase activity	TAS Reactome:R-HSA-193997	ACCEPT	Summary: Reactome (TAS) annotation from the reaction "CYP11B1 oxidises 11DCORT" (11-deoxycortisol to cortisol), the core catalytic activity. Reason: Correct and specific molecular function, curator-asserted from the Reactome reaction. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt 11beta position, yielding cortisol or corticosterone, respectively, but
GO:0004507 steroid 11-beta-monooxygenase activity	TAS Reactome:R-HSA-5580292	ACCEPT	Summary: Reactome (TAS) annotation from the disease reaction "Defective CYP11B1 does not oxidise 11DCORT", capturing the same 11beta-hydroxylase molecular function in the context of AH4. Reason: Correct and specific molecular function; the disease-context Reactome event asserts the same steroid 11-beta-monooxygenase activity. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt 11beta position, yielding cortisol or corticosterone, respectively, but
GO:0004507 steroid 11-beta-monooxygenase activity	IDA PMID:18215163 Purification and functional characterization of human 11beta...	ACCEPT	Summary: Direct experimental demonstration: purified recombinant human CYP11B1 hydroxylates its substrates at the 11beta position, converting 11-deoxycortisol to cortisol. Reason: Strong experimental (IDA) support for the core molecular function, from purified-enzyme substrate-conversion assays. Supporting Evidence: PMID:18215163 The results clearly demonstrate that the enzyme is capable of hydroxylating its substrates at position 11-beta.
GO:0034651 cortisol biosynthetic process	IDA PMID:18215163 Purification and functional characterization of human 11beta...	ACCEPT	Summary: Direct experimental support that CYP11B1 carries out the cortisol-forming step (11-deoxycortisol -> cortisol), the core biological process. Reason: Experimentally demonstrated with purified enzyme; the defining physiological role of CYP11B1. Supporting Evidence: PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol.
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation (from ortholog P14137) to the mitochondrial inner membrane, matching the curated location. Reason: Correct core location; consistent with the experimental IC/TAS and electronic annotations to the same term. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial proteomics detected CYP11B1 in the mitochondrion, supporting the mitochondrial localization. Reason: Consistent with the curated mitochondrial inner-membrane location; a valid, if broad, localization from a high-confidence proteomics dataset. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-5580292	ACCEPT	Summary: Reactome (TAS) annotation placing CYP11B1 at the mitochondrial inner membrane, matching the curated location. Reason: Correct core location; concordant with the multiple other inner-membrane annotations. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0035865 cellular response to potassium ion	IEP PMID:19342457 Regulation of aldosterone and cortisol production by the tra...	KEEP AS NON CORE	Summary: Expression-based (IEP) annotation from a study of NRSF/NRSE regulation of CYP11B1 and CYP11B2, in which potassium (and angiotensin II) augment CYP11B1/CYP11B2 transcription in H295R adrenocortical cells. Potassium sensing is more central to aldosterone (CYP11B2) than to cortisol (CYP11B1). Reason: The full-text study co-assays CYP11B1, so the annotation is retained (not removed), but the potassium response is a regulatory/physiological context that is more salient for the aldosterone-synthase paralog; it is peripheral to CYP11B1's core cortisol-synthesis role. Supporting Evidence: PMID:19342457 NRSF/NRSE is also involved in angiotensin II- and K(+)-stimulated augmentation of CYP11B2 and CYP11B1 gene transcription
GO:0032342 aldosterone biosynthetic process	IMP PMID:19342457 Regulation of aldosterone and cortisol production by the tra...	MARK AS OVER ANNOTATED	Summary: Mutant/perturbation-phenotype annotation associating CYP11B1 with aldosterone production, from a transcriptional-regulation study in which the NRSF perturbation affected both CYP11B2 (aldosterone) and CYP11B1 (cortisol). Human CYP11B1 does not itself synthesize aldosterone. Reason: The paper measures aldosterone and cortisol secretion after modulating the shared NRSF/NRSE regulator; aldosterone output reflects CYP11B2 activity, not a CYP11B1 catalytic role. CYP11B1 cannot make aldosterone, so annotating it to aldosterone biosynthesis over-states its function. Supporting Evidence: PMID:19342457 Aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) regulate aldosterone and cortisol production, respectively. PMID:2256920 P-450(11)beta substantially fails to catalyze the
GO:0032870 cellular response to hormone stimulus	IEP PMID:19342457 Regulation of aldosterone and cortisol production by the tra...	KEEP AS NON CORE	Summary: Expression-based annotation reflecting that CYP11B1 transcription responds to hormonal stimuli (e.g. angiotensin II) in adrenocortical cells. Reason: A regulatory/physiological response context rather than the enzyme's core molecular function; retained as non-core. The more specific "cellular response to peptide hormone stimulus" (ACTH) captures the principal trophic input. Supporting Evidence: PMID:19342457 NRSF/NRSE is also involved in angiotensin II- and K(+)-stimulated augmentation of CYP11B2 and CYP11B1 gene transcription
GO:0034651 cortisol biosynthetic process	IMP PMID:19342457 Regulation of aldosterone and cortisol production by the tra...	ACCEPT	Summary: Mutant/perturbation-phenotype annotation: modulating NRSF changed CYP11B1 expression and cortisol secretion, linking CYP11B1 to cortisol production. Reason: Core biological process; the study demonstrates CYP11B1-dependent cortisol output in human adrenocortical cells, consistent with the enzyme's defining role. Supporting Evidence: PMID:19342457 Aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) regulate aldosterone and cortisol production, respectively.
GO:0034651 cortisol biosynthetic process	IMP PMID:2022736 A mutation in CYP11B1 (Arg-448	ACCEPT	Summary: Mutant-phenotype annotation: an Arg-448->His mutation in CYP11B1 causes steroid 11beta-hydroxylase deficiency, i.e. failure to convert 11-deoxycortisol to cortisol, linking loss of CYP11B1 function to loss of cortisol biosynthesis. Reason: Human genetic loss-of-function evidence directly supports CYP11B1's role in cortisol biosynthesis (the deficiency is defined as failure to convert 11-deoxycortisol to cortisol). Supporting Evidence: PMID:2022736 Steroid 11 beta-hydroxylase (P450c11) deficiency (failure to convert 11-deoxycortisol to cortisol) causes less than 10% of cases of congenital adrenal hyperplasia
GO:0034651 cortisol biosynthetic process	IDA PMID:8506298 Mutations in the CYP11B1 gene causing congenital adrenal hyp...	ACCEPT	Summary: In-vitro transfection assays of CYP11B1 missense mutants (which abolish enzyme activity) support CYP11B1's role in converting 11-deoxycortisol to cortisol. Reason: Experimental support: the study defines 11beta-hydroxylase deficiency as failure to convert 11-deoxycortisol to cortisol and shows the missense mutations abolish enzymatic activity, confirming the cortisol-biosynthetic function. Supporting Evidence: PMID:8506298 Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) PMID:8506298 all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity
GO:0004507 steroid 11-beta-monooxygenase activity	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Direct assay of the cloned/expressed enzyme in COS-7 cells demonstrating steroid 11beta-hydroxylase activity (formation of corticosterone from 11-deoxycorticosterone). Reason: Experimental (IDA) support for the core molecular function. The paper's primary focus is P-450aldo (CYP11B2), but it directly compares and assays P-450(11)beta (CYP11B1), which catalyzes 11beta-hydroxylation. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate
GO:0005743 mitochondrial inner membrane	TAS PMID:15026188 Modulation of aldosterone and cortisol synthesis on the mole...	ACCEPT	Summary: Review (TAS) asserting the mitochondrial (inner-membrane) localization of the class I mitochondrial cytochrome P450 CYP11B1. Reason: Correct core location; the review describes CYP11B1 as a class I mitochondrial cytochrome P450 that receives electrons from the adrenodoxin system. Supporting Evidence: PMID:15026188 The CYP11B family belongs to class I cytochromes P450 that have been described in bacteria and mitochondria
GO:0005743 mitochondrial inner membrane	IC PMID:8506298 Mutations in the CYP11B1 gene causing congenital adrenal hyp...	ACCEPT	Summary: Curator-inferred (IC) mitochondrial inner-membrane localization, based on the steroid 11-beta-monooxygenase activity (GO:0004507) of this mitochondrial P450. Reason: Consistent with all other localization evidence; CYP11B1 is a mitochondrial inner-membrane enzyme. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0006700 C21-steroid hormone biosynthetic process	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Direct assay showing CYP11B1 (P-450(11)beta) produces the C21 steroid corticosterone from 11-deoxycorticosterone, supporting a role in C21-steroid hormone biosynthesis. Reason: Cortisol and corticosterone are C21 steroids; CYP11B1's products place it correctly in C21-steroid hormone biosynthesis. Experimentally supported. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate
GO:0006955 immune response	TAS PMID:12452430 The human steroid hydroxylases CYP1B1 and CYP11B2.	MARK AS OVER ANNOTATED	Summary: Review (TAS) annotation to immune response. Glucocorticoids (cortisol) are potent immunomodulators, but this is a downstream physiological effect of CYP11B1's product, not a molecular/cellular function of the enzyme itself. Reason: CYP11B1 does not itself participate in the immune response; the connection is indirect, via the anti-inflammatory/immunomodulatory actions of the cortisol it produces. Annotating the enzyme to "immune response" over-extends its function. Supporting Evidence: PMID:12452430 the human mitochondrial cytochrome P450 enzymes CYP11B1 and CYP11B2, which catalyze the final steps in the biosynthesis of cortisol and aldosterone
GO:0008217 regulation of blood pressure	IMP PMID:2022736 A mutation in CYP11B1 (Arg-448	KEEP AS NON CORE	Summary: Mutant-phenotype annotation linking CYP11B1 deficiency to a hypertensive form of congenital adrenal hyperplasia. Loss of 11beta-hydroxylase causes accumulation of the mineralocorticoid precursor 11-deoxycorticosterone, driving hypertension. Reason: A genuine but downstream physiological consequence of CYP11B1 dysfunction (via DOC excess) rather than a direct enzymatic function; retained as non-core. Supporting Evidence: PMID:8506298 Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is the second most common cause of congenital adrenal hyperplasia and results in a hypertensive form of the disease.
GO:0020037 heme binding	IC PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Curator-inferred (IC) heme binding, from the steroid 11-beta-monooxygenase activity of this heme-thiolate cytochrome P450. Reason: Correct core cofactor-binding function; CYP11B1 binds heme via an axial cysteine ligand and requires it for catalysis. A mutation in the heme-binding peptide (Arg-448->His) causes deficiency. Supporting Evidence: PMID:2022736 This residue is within the "heme binding" peptide that contains a cysteine that is a ligand to the heme group.
GO:0032342 aldosterone biosynthetic process	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	MARK AS OVER ANNOTATED	Summary: Annotation to aldosterone biosynthesis from a study whose primary aldosterone-forming enzyme is P-450aldo (CYP11B2). The same paper shows P-450(11)beta (CYP11B1) substantially fails to form aldosterone. Reason: Although CYP11B1 shares 93% identity with CYP11B2 and can make corticosterone precursors, this reference explicitly states CYP11B1 substantially fails to catalyze the reaction to form aldosterone. Aldosterone biosynthesis is the function of CYP11B2, so this is an over-annotation for CYP11B1. Supporting Evidence: PMID:2256920 P-450(11)beta substantially fails to catalyze the reaction to form aldosterone
GO:0004507 steroid 11-beta-monooxygenase activity	IMP PMID:2022736 A mutation in CYP11B1 (Arg-448	ACCEPT	Summary: Mutant-phenotype annotation: the Arg-448->His mutation in the heme-binding region abolishes/impairs steroid 11beta-hydroxylase activity, supporting the molecular function. Reason: Human loss-of-function genetics supports the steroid 11-beta-monooxygenase activity; the mutation lies in the heme-binding peptide and is expected to disrupt catalysis. Supporting Evidence: PMID:2022736 it seems likely that a mutation of this residue would adversely affect enzymatic activity
GO:0004507 steroid 11-beta-monooxygenase activity	IDA PMID:8506298 Mutations in the CYP11B1 gene causing congenital adrenal hyp...	ACCEPT	Summary: In-vitro transfection assays show that missense mutations causing 11beta-hydroxylase deficiency abolish enzymatic activity, directly supporting the steroid 11-beta-monooxygenase molecular function. Reason: Experimental (IDA) support for the core molecular function via functional assays of wild-type versus mutant CYP11B1. Supporting Evidence: PMID:8506298 all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity
GO:0005739 mitochondrion	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Direct-assay localization of the expressed enzyme to the mitochondrion. Reason: Consistent with the curated mitochondrial inner-membrane location; a valid broad localization. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane
GO:0042593 glucose homeostasis	TAS PMID:16114325 [Hypoglycemia due to a disorder of adrenal cortical regulati...	KEEP AS NON CORE	Summary: Review/case (TAS) annotation to glucose homeostasis, reflecting that cortisol (a glucocorticoid produced via CYP11B1) raises blood glucose and its deficiency can cause hypoglycemia. Reason: A downstream physiological role of the cortisol product (glucocorticoids promote gluconeogenesis), not a direct enzymatic function of CYP11B1. Retained as non-core. Supporting Evidence: PMID:16114325 Hypoglycemia due to a disorder of adrenal cortical regulation
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-193997	ACCEPT	Summary: Reactome (TAS) annotation placing CYP11B1 at the mitochondrial inner membrane in the "CYP11B1 oxidises 11DCORT" reaction. Reason: Correct core location; concordant with the multiple other inner-membrane annotations and the Reactome statement that CYP11B1 is associated with the inner mitochondrial membrane. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt Mitochondrion inner membrane

Gene Description

Existing Annotations Review

Core Functions

Steroid 11-beta-monooxygenase (11beta-hydroxylase) catalysing the final step of cortisol biosynthesis at the mitochondrial inner membrane, converting 11-deoxycortisol to cortisol (and 11-deoxycorticosterone to corticosterone), using heme and the adrenodoxin electron system.

Heme cofactor binding required for oxygen activation by this heme-thiolate cytochrome P450 (axial cysteine ligand at position 450). Secondary to the catalytic 11-beta-monooxygenase function.

References

📚 Additional Documentation

Notes

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