CYP11B2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006704 glucocorticoid biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA transfer of glucocorticoid biosynthesis across the CYP11B/CYP27 clade. In humans the physiological glucocorticoid (cortisol) producer is the paralog CYP11B1, not CYP11B2; CYP11B2 physiologically makes the mineralocorticoid aldosterone. CYP11B2 can produce cortisol from 11-deoxycortisol in vitro, but this is not its physiological role. Reason: The 93%-identical paralogs CYP11B1 and CYP11B2 have distinct physiological roles; CYP11B2 participates in mineralocorticoid (aldosterone) synthesis while CYP11B1 makes glucocorticoids. The IBA over-broadens a clade-level glucocorticoid role onto the aldosterone synthase. Kept (not removed) as it reflects a low-level in-vitro activity, but flagged as over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Supporting Evidence: PMID:1741400 the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.
GO:0034650 cortisol metabolic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA cortisol metabolic process, transferred across the CYP11B clade. As with glucocorticoid biosynthesis, physiological cortisol handling is the role of CYP11B1; CYP11B2's physiological product is aldosterone. Reason: Cortisol metabolism is not the physiological role of CYP11B2 (that is CYP11B1). CYP11B2 can act on cortisol in vitro (producing 18-hydroxycortisol and 18-oxocortisol, elevated in primary aldosteronism), so the term is not strictly wrong, but it over-broadens a clade-level role and is not core. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Supporting Evidence: PMID:1741400 the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.
GO:0004507 steroid 11-beta-monooxygenase activity	IBA GO_REF:0000033	ACCEPT	Summary: Steroid 11-beta-monooxygenase (EC 1.14.15.4) activity, transferred by phylogeny. This is a genuine core catalytic activity of CYP11B2: it 11-beta-hydroxylates 11-deoxycorticosterone to corticosterone as the first of its three sequential reactions toward aldosterone. Reason: Directly supported by biochemistry and structure of human aldosterone synthase; the IBA is at an appropriate level of specificity for this MF. Supporting Evidence: PMID:23322723 explains the high 11β-hydroxylase activity of aldosterone synthase toward both gluco- and mineralocorticoid formation
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial inner membrane localization (is_active_in), by phylogeny. CYP11B2 is a mitochondrial inner-membrane P450 that receives electrons from the matrix-facing adrenodoxin system; this is its correct site of action. Reason: Consistent with UniProt subcellular location and Reactome, which place the catalysis at the inner mitochondrial membrane. Core cellular component. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane Reactome:R-HSA-193995 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0032342 aldosterone biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Aldosterone biosynthetic process, by phylogeny. This is the defining biological role of CYP11B2 - it catalyzes the terminal reactions producing aldosterone in the adrenal zona glomerulosa. Reason: Core biological process; well supported experimentally and by the enzyme's unique 18-oxidase capability among the CYP11B isozymes. Supporting Evidence: PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0071375 cellular response to peptide hormone stimulus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Cellular response to peptide hormone stimulus, by phylogeny. CYP11B2 transcription is induced by angiotensin II (a peptide hormone), consistent with regulation of aldosterone output by the renin-angiotensin system. Reason: Reflects transcriptional regulation of the gene by angiotensin II rather than a molecular function of the protein; a real but peripheral/regulatory process, not the enzyme's core function. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Expression is induced by angiotensin II
GO:0008203 cholesterol metabolic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Cholesterol metabolic process, transferred across the clade (which includes the cholesterol side-chain cleavage enzyme CYP11A1). CYP11B2 acts on C21 steroids (deoxycorticosterone and downstream intermediates), well downstream of cholesterol, and does not itself metabolize cholesterol. Reason: Over-broad IBA inherited from cholesterol-metabolizing relatives in the CYP11 family. CYP11B2's substrates are corticosteroids, not cholesterol. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: FUNCTIONAL DIVERGENCE GRANULARITY MISMATCH Supporting Evidence: PMID:23322723 The structures reveal a hydrophobic cavity with specific features associated with corticosteroid recognition.
GO:0047783 corticosterone 18-monooxygenase activity	IBA GO_REF:0000033	ACCEPT	Summary: Corticosterone 18-monooxygenase / aldosterone synthase activity (EC 1.14.15.5), by phylogeny. This is the diagnostic core activity of CYP11B2: 18-hydroxylation of corticosterone and subsequent 18-oxidation, the steps that distinguish aldosterone synthase from CYP11B1 and yield aldosterone. Reason: Defining molecular function; the additional 18-oxidase activity is the feature that separates CYP11B2 from the otherwise near-identical CYP11B1. Supporting Evidence: PMID:23322723 most of the divergent residues that confer additional 18-oxidase activity of aldosterone synthase are located in the PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0004497 monooxygenase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO monooxygenase activity from cytochrome P450 domain signatures. Correct general P450 activity; a parent of the specific steroid monooxygenase functions CYP11B2 performs. Reason: Accurate general molecular function inferred from P450 domains; broader than the specific EC-level terms but not misleading. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Aldosterone synthase
GO:0004507 steroid 11-beta-monooxygenase activity	IEA GO_REF:0000120	ACCEPT	Summary: UniProt automatic (RHEA/EC 1.14.15.4) mapping to steroid 11-beta-monooxygenase activity. Consistent with the experimentally established 11-beta-hydroxylase activity of CYP11B2. Reason: Correct EC-based electronic annotation matching curated catalytic activity. Supporting Evidence: PMID:23322723 explains the high 11β-hydroxylase activity of aldosterone synthase toward both gluco- and mineralocorticoid formation
GO:0005506 iron ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO iron ion binding, from the P450 heme-iron center. CYP11B2 binds a heme whose iron is coordinated by an axial cysteine thiolate (Cys450). Reason: Correct; the catalytic heme iron is an integral cofactor. Secondary/enabling molecular function supporting the monooxygenase chemistry. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt /ligand_part="Fe"
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: UniProt automatic mitochondrion localization. Correct but less specific than the mitochondrial inner membrane where CYP11B2 acts. Reason: Accurate parent localization; the more informative term is mitochondrial inner membrane (also annotated). Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location keyword mapping to mitochondrial inner membrane. This is the specific, correct site of CYP11B2 action. Reason: Matches curated UniProt subcellular location and Reactome; core CC. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane
GO:0016125 sterol metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic annotation to sterol metabolic process. CYP11B2 metabolizes C21 corticosteroids (deoxycorticosterone and downstream intermediates), not free sterols/cholesterol. Reason: Over-broad rule-based annotation inherited from steroidogenic P450 context; the enzyme's substrates are corticosteroids, not sterols per se. Supporting Evidence: PMID:23322723 The structures reveal a hydrophobic cavity with specific features associated with corticosteroid recognition.
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO oxidoreductase activity (paired-donor, O2-incorporating), i.e. the general monooxygenase chemistry of a P450. Accurate parent term. Reason: Correct general catalytic class for a cytochrome P450 monooxygenase. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the
GO:0020037 heme binding	IEA GO_REF:0000120	ACCEPT	Summary: UniProt automatic heme binding annotation. CYP11B2 is a heme-thiolate cytochrome P450; heme is its catalytic cofactor. Reason: Correct; supported experimentally by the crystal structure with heme. Secondary/enabling function underlying the monooxygenase activity. Supporting Evidence: PMID:23322723 we present the crystal structures of human aldosterone synthase in complex with a substrate deoxycorticosterone
GO:0032342 aldosterone biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to aldosterone biosynthetic process, consistent with the enzyme's defining physiological role. Reason: Correct core BP, corroborating the experimental and phylogenetic annotations. Supporting Evidence: PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0047783 corticosterone 18-monooxygenase activity	IEA GO_REF:0000120	ACCEPT	Summary: UniProt automatic (RHEA/EC 1.14.15.5) mapping to corticosterone 18-monooxygenase (aldosterone synthase) activity. Matches curated catalytic activity and is the diagnostic CYP11B2 function. Reason: Correct EC-based electronic annotation of the defining 18-oxidase activity. Supporting Evidence: PMID:23322723 most of the divergent residues that confer additional 18-oxidase activity of aldosterone synthase are located in the
GO:0006705 mineralocorticoid biosynthetic process	TAS Reactome:R-HSA-193993	ACCEPT	Summary: Reactome TAS to mineralocorticoid biosynthetic process. Aldosterone is the major human mineralocorticoid, synthesized from deoxycorticosterone in a three-reaction sequence catalyzed by CYP11B2. Reason: Correct core BP (parent of aldosterone biosynthesis); authoritative Reactome pathway assertion. Supporting Evidence: Reactome:R-HSA-193993 which in turn is converted to aldosterone in a three-reaction sequence catalyzed by CYP11B2
GO:0016125 sterol metabolic process	TAS Reactome:R-HSA-211976	MARK AS OVER ANNOTATED	Summary: Reactome "Endogenous sterols" TAS grouping many CYPs under sterol metabolism. CYP11B2 acts on corticosteroids rather than free sterols; the grouping is over-broad for this specific enzyme. Reason: Pathway-grouping annotation; too general for the corticosteroid-specific catalysis of CYP11B2. Supporting Evidence: PMID:23322723 The structures reveal a hydrophobic cavity with specific features associated with corticosteroid recognition.
GO:0004507 steroid 11-beta-monooxygenase activity	TAS Reactome:R-HSA-194017	ACCEPT	Summary: Reactome TAS for the reaction "CYP11B2 oxidises 11DCORST to CORST" - 11-beta-hydroxylation of 11-deoxycorticosterone to corticosterone. Reason: Correct core MF backed by an authoritative Reactome reaction. Supporting Evidence: Reactome:R-HSA-194017 The 11-beta oxidation of 11-deoxycorticosterone (11DCORST) leads to corticosterone (CORST)
GO:0004507 steroid 11-beta-monooxygenase activity	TAS Reactome:R-HSA-5600598	ACCEPT	Summary: Reactome TAS (disease reaction "Defective CYP11B2 does not oxidise 11DCORST") annotating the normal 11-beta-monooxygenase activity of CYP11B2. Reason: Correct core MF; duplicate of the same activity from a disease-variant reaction, but the underlying enzymatic assertion is sound. Supporting Evidence: Reactome:R-HSA-5600598 CYP11B2 aka aldosterone hydroxylase) is an enzyme necessary for aldosterone biosynthesis via corticosterone (CORST)
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: ISS transfer of mitochondrial inner-membrane localization from an ortholog (UniProtKB:P14137, bovine CYP11B). Consistent with human UniProt location. Reason: Correct core CC, corroborated by curated UniProt subcellular location and Reactome. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial-proteome detection places CYP11B2 in the mitochondrion. Consistent with its known mitochondrial inner-membrane localization. Reason: Correct, corroborating mitochondrial localization; less specific than the inner-membrane term. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-5600598	ACCEPT	Summary: Reactome TAS placing CYP11B2 catalysis at the mitochondrial inner membrane. Reason: Correct core CC from an authoritative pathway source. Supporting Evidence: Reactome:R-HSA-193995 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6785244	ACCEPT	Summary: Reactome TAS (disease reaction) placing CYP11B2 at the mitochondrial inner membrane. Reason: Correct core CC; duplicate localization from a disease-variant reaction. Supporting Evidence: Reactome:R-HSA-193995 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6785245	ACCEPT	Summary: Reactome TAS (disease reaction) placing CYP11B2 at the mitochondrial inner membrane. Reason: Correct core CC; duplicate localization from a disease-variant reaction. Supporting Evidence: Reactome:R-HSA-193995 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-193965	ACCEPT	Summary: Reactome TAS (reaction "CYP11B2 oxidises 18HCORST to ALDO") placing CYP11B2 at the mitochondrial inner membrane. Reason: Correct core CC from an authoritative pathway reaction. Supporting Evidence: Reactome:R-HSA-193965 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-193995	ACCEPT	Summary: Reactome TAS (reaction "CYP11B2 18-hydroxylates CORST to 18HCORST") placing CYP11B2 at the mitochondrial inner membrane. Reason: Correct core CC from an authoritative pathway reaction. Supporting Evidence: Reactome:R-HSA-193995 This reaction is catalyzed by CYP11B2 associated with the inner mitochondrial membrane.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-194017	ACCEPT	Summary: Reactome TAS (reaction "CYP11B2 oxidises 11DCORST to CORST") placing CYP11B2 at the mitochondrial inner membrane. Reason: Correct core CC from an authoritative pathway reaction. Supporting Evidence: Reactome:R-HSA-194017 Cytochrome P450 11B2, mitochondrial
GO:0008395 steroid hydroxylase activity	TAS Reactome:R-HSA-193965	ACCEPT	Summary: Reactome TAS grouping CYP11B2's activity under steroid hydroxylase activity. Correct parent term encompassing its 11-beta- and 18-hydroxylase activities. Reason: Accurate grouping MF; the specific EC-level terms (11-beta- and 18-monooxygenase) are the more informative core functions. Supporting Evidence: Reactome:R-HSA-193965 18-Hydroxycorticosterone and NADPH + H+ react to form aldosterone
GO:0008395 steroid hydroxylase activity	TAS Reactome:R-HSA-193995	ACCEPT	Summary: Reactome TAS grouping CYP11B2 under steroid hydroxylase activity (from the 18-hydroxylation reaction). Correct parent term. Reason: Accurate grouping MF; duplicate of the same activity from another reaction. Supporting Evidence: Reactome:R-HSA-193995 Corticosterone, NADPH + H+, and O2 react to form 18-hydroxycorticosterone
GO:0008395 steroid hydroxylase activity	TAS Reactome:R-HSA-6785244	ACCEPT	Summary: Reactome TAS (disease reaction) grouping CYP11B2 under steroid hydroxylase activity. Reason: Accurate grouping MF; duplicate from a disease-variant reaction. Supporting Evidence: Reactome:R-HSA-6785244 CYP11B2 aka aldosterone hydroxylase) is an enzyme necessary for aldosterone biosynthesis
GO:0008395 steroid hydroxylase activity	TAS Reactome:R-HSA-6785245	ACCEPT	Summary: Reactome TAS (disease reaction) grouping CYP11B2 under steroid hydroxylase activity. Reason: Accurate grouping MF; duplicate from a disease-variant reaction. Supporting Evidence: Reactome:R-HSA-6785245 CYP11B2 aka aldosterone hydroxylase) is an enzyme necessary for aldosterone biosynthesis
GO:0004507 steroid 11-beta-monooxygenase activity	IDA PMID:23322723 Structural insights into aldosterone synthase substrate spec...	ACCEPT	Summary: Direct assay/structure of human aldosterone synthase demonstrating high 11-beta-hydroxylase activity, with the substrate deoxycorticosterone bound in the crystal structure. Reason: Strong experimental (IDA) support from crystallography plus biochemistry. Core molecular function. Supporting Evidence: PMID:23322723 explains the high 11β-hydroxylase activity of aldosterone synthase toward both gluco- and mineralocorticoid formation
GO:0020037 heme binding	IDA PMID:23322723 Structural insights into aldosterone synthase substrate spec...	ACCEPT	Summary: Direct structural demonstration of heme binding: the crystal structures contain the heme cofactor with iron coordinated by an axial cysteine. Reason: Experimentally confirmed cofactor binding (IDA); secondary/enabling MF underlying the monooxygenase catalysis. Supporting Evidence: PMID:23322723 we present the crystal structures of human aldosterone synthase in complex with a substrate deoxycorticosterone
GO:0032342 aldosterone biosynthetic process	IDA PMID:23322723 Structural insights into aldosterone synthase substrate spec...	ACCEPT	Summary: Direct evidence that CYP11B2 is the sole enzyme producing aldosterone in humans, catalyzing formation of aldosterone from deoxycorticosterone. Reason: Core BP supported by direct biochemical/structural study. Supporting Evidence: PMID:23322723 Aldosterone synthase (cytochrome P450 11B2, CYP11B2) is the sole enzyme responsible for the production of aldosterone in humans.
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-pattern (IEP) evidence that CYP11B2 transcription responds to extracellular potassium (K+), via T-type calcium channel (Cav3.2/CACNA1H) signaling and NRSF/NRSE regulation, increasing aldosterone output. Reason: Reflects transcriptional/physiological regulation of the gene by K+ rather than a molecular activity of the enzyme; real but peripheral to core function. 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...	ACCEPT	Summary: Mutation/perturbation (IMP) evidence: modulating CYP11B2 expression (via NRSF inhibition) changes aldosterone secretion in human adrenocortical cells, supporting its role in aldosterone biosynthesis. Reason: Core BP; consistent with the enzyme's defining function. Supporting Evidence: PMID:19342457 increased human CYP11B2 and CYP11B1 mRNA expression, leading to aldosterone and cortisol secretion in human adrenocortical (H295R) cells
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-pattern (IEP) evidence that CYP11B2 transcription responds to hormonal stimulation (e.g. angiotensin II), consistent with regulation of aldosterone production. Reason: Regulatory/physiological response term, not a molecular function of the protein; peripheral to core enzymatic role. 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...	MARK AS OVER ANNOTATED	Summary: IMP annotation to cortisol biosynthesis from a study where NRSF inhibition increased both CYP11B2 and CYP11B1 expression and both aldosterone and cortisol secretion in H295R cells. Physiological cortisol production is driven by the paralog CYP11B1, not CYP11B2. Reason: The cortisol readout in this experiment reflects the co-induced CYP11B1 (and possibly low-level in-vitro CYP11B2 activity), not the physiological role of CYP11B2. This is contradicted by the BHF-UCL NOT\|involved_in cortisol biosynthesis annotation and by the CYP11B1/CYP11B2 division of labor, so it is flagged as an over-annotation rather than a core function. Supporting Evidence: PMID:19342457 Aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) regulate aldosterone and cortisol production, respectively.
GO:0034651 cortisol biosynthetic process	IMP NOT PMID:9703385 Molecular genetic study in two patients with congenital hypo...	ACCEPT	Summary: NOT\|involved_in cortisol biosynthetic process. In CMO-deficiency patients, cortisol and its precursors are in the normal range despite defective aldosterone synthesis, indicating CYP11B2 is not required for cortisol production (that is the role of CYP11B1). Reason: Correct negation: CYP11B2 loss does not impair cortisol biosynthesis, consistent with the CYP11B1/CYP11B2 division of labor. This negated annotation is well supported and appropriately curated. Supporting Evidence: PMID:9703385 Plasma corticosterone and 11-deoxycorticosterone were elevated in both patients, whereas cortisol and its precursors were in the normal range.
GO:0002017 regulation of blood volume by renal aldosterone	IMP PMID:14614232 A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of th...	KEEP AS NON CORE	Summary: IMP from CMO-II deficiency patients: CYP11B2 loss-of-function reduces aldosterone, causing salt-wasting and disturbed volume/electrolyte balance, linking the enzyme to aldosterone-mediated regulation of blood volume. Reason: A downstream physiological consequence of aldosterone production, not the enzyme's molecular core function; retained as a non-core organismal role. Supporting Evidence: PMID:14614232 Japanese patients newly diagnosed with CMO II deficiency
GO:0003091 renal water homeostasis	IC PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	KEEP AS NON CORE	Summary: Curator inference (IC, from aldosterone biosynthetic process) that CYP11B2, by producing aldosterone, contributes to renal water homeostasis. Reason: Downstream physiological consequence of aldosterone action on the kidney; not the enzyme's molecular core function. Supporting Evidence: PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0004507 steroid 11-beta-monooxygenase activity	IDA PMID:1741400 Role of steroid 11 beta-hydroxylase and steroid 18-hydroxyla...	ACCEPT	Summary: Direct assay: CYP11B2 (P-450C18) expressed in COS-7 cells exhibits steroid 11-beta-hydroxylase activity in addition to 18-hydroxylase activity. Reason: Core molecular function supported by direct heterologous-expression assay. Supporting Evidence: PMID:1741400 exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well.
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: P-450aldo (CYP11B2) expressed in COS-7 cells forms corticosterone from 11-deoxycorticosterone (11-beta-hydroxylation). Reason: Core molecular function supported by direct heterologous-expression assay. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate
GO:0005739 mitochondrion	IDA PMID:1741400 Role of steroid 11 beta-hydroxylase and steroid 18-hydroxyla...	ACCEPT	Summary: IDA mitochondrion localization from expression studies of CYP11B2, a mitochondrial P450. Consistent with the curated inner-membrane location. Reason: Correct localization; less specific than the mitochondrial inner membrane. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane
GO:0005743 mitochondrial inner membrane	IC PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Curator inference (IC, from steroid 11-beta-monooxygenase activity) placing CYP11B2 at the mitochondrial inner membrane, where mitochondrial P450s and the adrenodoxin electron system operate. Reason: Correct core CC; consistent with UniProt subcellular location and Reactome. Supporting Evidence: file:human/CYP11B2/CYP11B2-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: IDA to C21-steroid hormone biosynthesis: CYP11B2 synthesizes aldosterone (a C21 corticosteroid) from 11-deoxycorticosterone via corticosterone and 18-hydroxycorticosterone. Reason: Correct broader biosynthetic BP; aldosterone is a C21 steroid hormone. Supporting Evidence: PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0020037 heme binding	IC PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Curator inference (IC, from steroid 11-beta-monooxygenase activity) that CYP11B2 binds heme, as expected for a cytochrome P450. Reason: Correct; heme is the catalytic cofactor, later confirmed structurally (PMID:23322723). Secondary/enabling MF. Supporting Evidence: PMID:23322723 we present the crystal structures of human aldosterone synthase in complex with a substrate deoxycorticosterone
GO:0032342 aldosterone biosynthetic process	IDA PMID:1741400 Role of steroid 11 beta-hydroxylase and steroid 18-hydroxyla...	ACCEPT	Summary: Direct assay: CYP11B2 catalyzes the synthesis of aldosterone (via its 18-hydroxylase/18-oxidase activity), unlike CYP11B1 which cannot. Reason: Core BP directly demonstrated by heterologous expression. Supporting Evidence: PMID:1741400 exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol
GO:0032342 aldosterone biosynthetic process	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: Direct assay: P-450aldo (CYP11B2) preferentially converts 11-deoxycorticosterone to aldosterone, unlike P-450(11)beta (CYP11B1). Reason: Core BP directly demonstrated; this study distinguishes CYP11B2 from CYP11B1 by the aldosterone-forming capacity. Supporting Evidence: PMID:2256920 P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone
GO:0055075 potassium ion homeostasis	IMP PMID:9838244 Homozygous deletion of arginine-173 in the CYP11B2 gene in a...	KEEP AS NON CORE	Summary: IMP from a CMO-II deficiency patient with homozygous R173 deletion: loss of aldosterone synthase activity causes elevated plasma potassium (and low sodium), linking CYP11B2 to potassium homeostasis via aldosterone. Reason: Downstream physiological consequence of aldosterone deficiency, not the enzyme's molecular core function. Supporting Evidence: PMID:9838244 Important laboratory findings were low plasma sodium and elevated potassium and renin.
GO:0055078 sodium ion homeostasis	IMP PMID:9838244 Homozygous deletion of arginine-173 in the CYP11B2 gene in a...	KEEP AS NON CORE	Summary: IMP from a CMO-II deficiency patient: loss of aldosterone synthase causes salt-wasting with low plasma sodium, linking CYP11B2 to sodium homeostasis via aldosterone. Reason: Downstream physiological consequence of aldosterone deficiency, not the enzyme's molecular core function. Supporting Evidence: PMID:9838244 Salt wasting was caused by an enzymatic defect in the terminal aldosterone biosynthesis.
GO:0005739 mitochondrion	IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a...	ACCEPT	Summary: IDA mitochondrion localization from expression studies of P-450aldo (CYP11B2), a mitochondrial cytochrome P450. Reason: Correct localization; less specific than the mitochondrial inner membrane. Supporting Evidence: file:human/CYP11B2/CYP11B2-uniprot.txt Mitochondrion inner membrane

📄 View Raw YAML

id: P19099
gene_symbol: CYP11B2
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CYP11B2 (aldosterone synthase; cytochrome P450 11B2, also called P450c11AS /
  P450aldo / P450C18) is a mitochondrial inner-membrane, heme-thiolate cytochrome
  P450 monooxygenase expressed in the zona glomerulosa of the adrenal cortex. It
  catalyzes the final three sequential steps of mineralocorticoid biosynthesis on
  a single active site: 11-beta-hydroxylation of 11-deoxycorticosterone to
  corticosterone, 18-hydroxylation of corticosterone to 18-hydroxycorticosterone,
  and 18-oxidation to yield aldosterone, the principal mineralocorticoid governing
  sodium/potassium and water balance. Catalysis uses molecular oxygen and NADPH-
  derived electrons delivered by the mitochondrial adrenodoxin/adrenodoxin-reductase
  (ferredoxin FDX1/FDX2 and ferredoxin reductase FDXR) electron-transfer system.
  CYP11B2 is more than 93% identical to the glucocorticoid-forming 11-beta-
  hydroxylase CYP11B1, but unlike CYP11B1 it possesses the 18-oxidase activity
  required to convert 18-hydroxycorticosterone to aldosterone, which functionally
  distinguishes the two isozymes. Loss-of-function variants cause aldosterone
  synthase (corticosterone methyloxidase, CMO type I and type II) deficiency, a
  salt-wasting disorder, whereas a CYP11B1/CYP11B2 chimeric gene arising from
  unequal crossover causes glucocorticoid-remediable aldosteronism (familial
  hyperaldosteronism type I).
existing_annotations:
- term:
    id: GO:0006704
    label: glucocorticoid biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA transfer of glucocorticoid biosynthesis across the CYP11B/CYP27 clade.
      In humans the physiological glucocorticoid (cortisol) producer is the
      paralog CYP11B1, not CYP11B2; CYP11B2 physiologically makes the
      mineralocorticoid aldosterone. CYP11B2 can produce cortisol from
      11-deoxycortisol in vitro, but this is not its physiological role.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The 93%-identical paralogs CYP11B1 and CYP11B2 have distinct physiological
      roles; CYP11B2 participates in mineralocorticoid (aldosterone) synthesis
      while CYP11B1 makes glucocorticoids. The IBA over-broadens a clade-level
      glucocorticoid role onto the aldosterone synthase. Kept (not removed) as it
      reflects a low-level in-vitro activity, but flagged as over-annotation.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      - FUNCTIONAL_DIVERGENCE
    supported_by:
    - reference_id: PMID:1741400
      supporting_text: >-
        the former participates in the synthesis of glucocorticoids whereas the
        latter participates in the synthesis of mineralocorticoids in humans.
- term:
    id: GO:0034650
    label: cortisol metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA cortisol metabolic process, transferred across the CYP11B clade. As
      with glucocorticoid biosynthesis, physiological cortisol handling is the
      role of CYP11B1; CYP11B2's physiological product is aldosterone.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Cortisol metabolism is not the physiological role of CYP11B2 (that is
      CYP11B1). CYP11B2 can act on cortisol in vitro (producing 18-hydroxycortisol
      and 18-oxocortisol, elevated in primary aldosteronism), so the term is not
      strictly wrong, but it over-broadens a clade-level role and is not core.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      - FUNCTIONAL_DIVERGENCE
    supported_by:
    - reference_id: PMID:1741400
      supporting_text: >-
        the former participates in the synthesis of glucocorticoids whereas the
        latter participates in the synthesis of mineralocorticoids in humans.
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Steroid 11-beta-monooxygenase (EC 1.14.15.4) activity, transferred by
      phylogeny. This is a genuine core catalytic activity of CYP11B2: it
      11-beta-hydroxylates 11-deoxycorticosterone to corticosterone as the first
      of its three sequential reactions toward aldosterone.
    action: ACCEPT
    reason: >-
      Directly supported by biochemistry and structure of human aldosterone
      synthase; the IBA is at an appropriate level of specificity for this MF.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        explains the high 11β-hydroxylase activity of aldosterone synthase toward
        both gluco- and mineralocorticoid formation
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Mitochondrial inner membrane localization (is_active_in), by phylogeny.
      CYP11B2 is a mitochondrial inner-membrane P450 that receives electrons from
      the matrix-facing adrenodoxin system; this is its correct site of action.
    action: ACCEPT
    reason: >-
      Consistent with UniProt subcellular location and Reactome, which place the
      catalysis at the inner mitochondrial membrane. Core cellular component.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Aldosterone biosynthetic process, by phylogeny. This is the defining
      biological role of CYP11B2 - it catalyzes the terminal reactions producing
      aldosterone in the adrenal zona glomerulosa.
    action: ACCEPT
    reason: >-
      Core biological process; well supported experimentally and by the enzyme's
      unique 18-oxidase capability among the CYP11B isozymes.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0071375
    label: cellular response to peptide hormone stimulus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Cellular response to peptide hormone stimulus, by phylogeny. CYP11B2
      transcription is induced by angiotensin II (a peptide hormone), consistent
      with regulation of aldosterone output by the renin-angiotensin system.
    action: KEEP_AS_NON_CORE
    reason: >-
      Reflects transcriptional regulation of the gene by angiotensin II rather
      than a molecular function of the protein; a real but peripheral/regulatory
      process, not the enzyme's core function.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Expression is induced by angiotensin II
- term:
    id: GO:0008203
    label: cholesterol metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Cholesterol metabolic process, transferred across the clade (which includes
      the cholesterol side-chain cleavage enzyme CYP11A1). CYP11B2 acts on C21
      steroids (deoxycorticosterone and downstream intermediates), well downstream
      of cholesterol, and does not itself metabolize cholesterol.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-broad IBA inherited from cholesterol-metabolizing relatives in the
      CYP11 family. CYP11B2's substrates are corticosteroids, not cholesterol.
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      - GRANULARITY_MISMATCH
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        The structures reveal a hydrophobic cavity with specific features
        associated with corticosteroid recognition.
- term:
    id: GO:0047783
    label: corticosterone 18-monooxygenase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Corticosterone 18-monooxygenase / aldosterone synthase activity
      (EC 1.14.15.5), by phylogeny. This is the diagnostic core activity of
      CYP11B2: 18-hydroxylation of corticosterone and subsequent 18-oxidation,
      the steps that distinguish aldosterone synthase from CYP11B1 and yield
      aldosterone.
    action: ACCEPT
    reason: >-
      Defining molecular function; the additional 18-oxidase activity is the
      feature that separates CYP11B2 from the otherwise near-identical CYP11B1.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        most of the divergent residues that confer additional 18-oxidase activity
        of aldosterone synthase are located in the
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0004497
    label: monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO monooxygenase activity from cytochrome P450 domain signatures.
      Correct general P450 activity; a parent of the specific steroid
      monooxygenase functions CYP11B2 performs.
    action: ACCEPT
    reason: >-
      Accurate general molecular function inferred from P450 domains; broader than
      the specific EC-level terms but not misleading.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Aldosterone synthase
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      UniProt automatic (RHEA/EC 1.14.15.4) mapping to steroid
      11-beta-monooxygenase activity. Consistent with the experimentally
      established 11-beta-hydroxylase activity of CYP11B2.
    action: ACCEPT
    reason: >-
      Correct EC-based electronic annotation matching curated catalytic activity.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        explains the high 11β-hydroxylase activity of aldosterone synthase toward
        both gluco- and mineralocorticoid formation
- term:
    id: GO:0005506
    label: iron ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO iron ion binding, from the P450 heme-iron center. CYP11B2 binds
      a heme whose iron is coordinated by an axial cysteine thiolate (Cys450).
    action: ACCEPT
    reason: >-
      Correct; the catalytic heme iron is an integral cofactor. Secondary/enabling
      molecular function supporting the monooxygenase chemistry.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: /ligand_part="Fe"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      UniProt automatic mitochondrion localization. Correct but less specific than
      the mitochondrial inner membrane where CYP11B2 acts.
    action: ACCEPT
    reason: >-
      Accurate parent localization; the more informative term is mitochondrial
      inner membrane (also annotated).
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt subcellular-location keyword mapping to mitochondrial inner
      membrane. This is the specific, correct site of CYP11B2 action.
    action: ACCEPT
    reason: >-
      Matches curated UniProt subcellular location and Reactome; core CC.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0016125
    label: sterol metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic annotation to sterol metabolic process. CYP11B2 metabolizes
      C21 corticosteroids (deoxycorticosterone and downstream intermediates), not
      free sterols/cholesterol.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-broad rule-based annotation inherited from steroidogenic P450 context;
      the enzyme's substrates are corticosteroids, not sterols per se.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        The structures reveal a hydrophobic cavity with specific features
        associated with corticosteroid recognition.
- term:
    id: GO:0016705
    label: oxidoreductase activity, acting on paired donors, with incorporation or
      reduction of molecular oxygen
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO oxidoreductase activity (paired-donor, O2-incorporating),
      i.e. the general monooxygenase chemistry of a P450. Accurate parent term.
    action: ACCEPT
    reason: >-
      Correct general catalytic class for a cytochrome P450 monooxygenase.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: A cytochrome P450 monooxygenase that catalyzes the
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      UniProt automatic heme binding annotation. CYP11B2 is a heme-thiolate
      cytochrome P450; heme is its catalytic cofactor.
    action: ACCEPT
    reason: >-
      Correct; supported experimentally by the crystal structure with heme.
      Secondary/enabling function underlying the monooxygenase activity.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        we present the crystal structures of human
        aldosterone synthase in complex with a substrate deoxycorticosterone
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic annotation to aldosterone biosynthetic process, consistent
      with the enzyme's defining physiological role.
    action: ACCEPT
    reason: >-
      Correct core BP, corroborating the experimental and phylogenetic annotations.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0047783
    label: corticosterone 18-monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      UniProt automatic (RHEA/EC 1.14.15.5) mapping to corticosterone
      18-monooxygenase (aldosterone synthase) activity. Matches curated catalytic
      activity and is the diagnostic CYP11B2 function.
    action: ACCEPT
    reason: >-
      Correct EC-based electronic annotation of the defining 18-oxidase activity.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        most of the divergent residues that confer additional 18-oxidase activity
        of aldosterone synthase are located in the
- term:
    id: GO:0006705
    label: mineralocorticoid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193993
  qualifier: involved_in
  review:
    summary: >-
      Reactome TAS to mineralocorticoid biosynthetic process. Aldosterone is the
      major human mineralocorticoid, synthesized from deoxycorticosterone in a
      three-reaction sequence catalyzed by CYP11B2.
    action: ACCEPT
    reason: >-
      Correct core BP (parent of aldosterone biosynthesis); authoritative
      Reactome pathway assertion.
    supported_by:
    - reference_id: Reactome:R-HSA-193993
      supporting_text: >-
        which in turn
        is converted to aldosterone in a three-reaction sequence catalyzed by
        CYP11B2
- term:
    id: GO:0016125
    label: sterol metabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-211976
  qualifier: involved_in
  review:
    summary: >-
      Reactome "Endogenous sterols" TAS grouping many CYPs under sterol
      metabolism. CYP11B2 acts on corticosteroids rather than free sterols; the
      grouping is over-broad for this specific enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Pathway-grouping annotation; too general for the corticosteroid-specific
      catalysis of CYP11B2.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        The structures reveal a hydrophobic cavity with specific features
        associated with corticosteroid recognition.
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-194017
  qualifier: enables
  review:
    summary: >-
      Reactome TAS for the reaction "CYP11B2 oxidises 11DCORST to CORST" -
      11-beta-hydroxylation of 11-deoxycorticosterone to corticosterone.
    action: ACCEPT
    reason: >-
      Correct core MF backed by an authoritative Reactome reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-194017
      supporting_text: >-
        The 11-beta oxidation of 11-deoxycorticosterone
        (11DCORST) leads to corticosterone (CORST)
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5600598
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (disease reaction "Defective CYP11B2 does not oxidise
      11DCORST") annotating the normal 11-beta-monooxygenase activity of CYP11B2.
    action: ACCEPT
    reason: >-
      Correct core MF; duplicate of the same activity from a disease-variant
      reaction, but the underlying enzymatic assertion is sound.
    supported_by:
    - reference_id: Reactome:R-HSA-5600598
      supporting_text: >-
        CYP11B2 aka aldosterone hydroxylase)
        is an enzyme necessary for aldosterone biosynthesis via corticosterone
        (CORST)
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      ISS transfer of mitochondrial inner-membrane localization from an ortholog
      (UniProtKB:P14137, bovine CYP11B). Consistent with human UniProt location.
    action: ACCEPT
    reason: >-
      Correct core CC, corroborated by curated UniProt subcellular location and
      Reactome.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput mitochondrial-proteome detection places CYP11B2 in the
      mitochondrion. Consistent with its known mitochondrial inner-membrane
      localization.
    action: ACCEPT
    reason: >-
      Correct, corroborating mitochondrial localization; less specific than the
      inner-membrane term.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5600598
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS placing CYP11B2 catalysis at the mitochondrial inner membrane.
    action: ACCEPT
    reason: >-
      Correct core CC from an authoritative pathway source.
    supported_by:
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785244
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (disease reaction) placing CYP11B2 at the mitochondrial inner
      membrane.
    action: ACCEPT
    reason: >-
      Correct core CC; duplicate localization from a disease-variant reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785245
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (disease reaction) placing CYP11B2 at the mitochondrial inner
      membrane.
    action: ACCEPT
    reason: >-
      Correct core CC; duplicate localization from a disease-variant reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193965
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (reaction "CYP11B2 oxidises 18HCORST to ALDO") placing CYP11B2
      at the mitochondrial inner membrane.
    action: ACCEPT
    reason: >-
      Correct core CC from an authoritative pathway reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-193965
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193995
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (reaction "CYP11B2 18-hydroxylates CORST to 18HCORST") placing
      CYP11B2 at the mitochondrial inner membrane.
    action: ACCEPT
    reason: >-
      Correct core CC from an authoritative pathway reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        This reaction is catalyzed by CYP11B2 associated with the inner
        mitochondrial membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-194017
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (reaction "CYP11B2 oxidises 11DCORST to CORST") placing CYP11B2
      at the mitochondrial inner membrane.
    action: ACCEPT
    reason: >-
      Correct core CC from an authoritative pathway reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-194017
      supporting_text: >-
        Cytochrome P450 11B2, mitochondrial
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193965
  qualifier: enables
  review:
    summary: >-
      Reactome TAS grouping CYP11B2's activity under steroid hydroxylase activity.
      Correct parent term encompassing its 11-beta- and 18-hydroxylase activities.
    action: ACCEPT
    reason: >-
      Accurate grouping MF; the specific EC-level terms (11-beta- and
      18-monooxygenase) are the more informative core functions.
    supported_by:
    - reference_id: Reactome:R-HSA-193965
      supporting_text: >-
        18-Hydroxycorticosterone and NADPH + H+ react to form aldosterone
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193995
  qualifier: enables
  review:
    summary: >-
      Reactome TAS grouping CYP11B2 under steroid hydroxylase activity (from the
      18-hydroxylation reaction). Correct parent term.
    action: ACCEPT
    reason: >-
      Accurate grouping MF; duplicate of the same activity from another reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-193995
      supporting_text: >-
        Corticosterone, NADPH + H+, and O2 react to form 18-hydroxycorticosterone
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785244
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (disease reaction) grouping CYP11B2 under steroid hydroxylase
      activity.
    action: ACCEPT
    reason: >-
      Accurate grouping MF; duplicate from a disease-variant reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-6785244
      supporting_text: >-
        CYP11B2 aka aldosterone hydroxylase)
        is an enzyme necessary for aldosterone biosynthesis
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785245
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (disease reaction) grouping CYP11B2 under steroid hydroxylase
      activity.
    action: ACCEPT
    reason: >-
      Accurate grouping MF; duplicate from a disease-variant reaction.
    supported_by:
    - reference_id: Reactome:R-HSA-6785245
      supporting_text: >-
        CYP11B2 aka aldosterone hydroxylase)
        is an enzyme necessary for aldosterone biosynthesis
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: IDA
  original_reference_id: PMID:23322723
  qualifier: enables
  review:
    summary: >-
      Direct assay/structure of human aldosterone synthase demonstrating high
      11-beta-hydroxylase activity, with the substrate deoxycorticosterone bound
      in the crystal structure.
    action: ACCEPT
    reason: >-
      Strong experimental (IDA) support from crystallography plus biochemistry.
      Core molecular function.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        explains the high 11β-hydroxylase activity of aldosterone synthase toward
        both gluco- and mineralocorticoid formation
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IDA
  original_reference_id: PMID:23322723
  qualifier: enables
  review:
    summary: >-
      Direct structural demonstration of heme binding: the crystal structures
      contain the heme cofactor with iron coordinated by an axial cysteine.
    action: ACCEPT
    reason: >-
      Experimentally confirmed cofactor binding (IDA); secondary/enabling MF
      underlying the monooxygenase catalysis.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        we present the crystal structures of human
        aldosterone synthase in complex with a substrate deoxycorticosterone
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:23322723
  qualifier: involved_in
  review:
    summary: >-
      Direct evidence that CYP11B2 is the sole enzyme producing aldosterone in
      humans, catalyzing formation of aldosterone from deoxycorticosterone.
    action: ACCEPT
    reason: >-
      Core BP supported by direct biochemical/structural study.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        Aldosterone
        synthase (cytochrome P450 11B2, CYP11B2) is the sole enzyme responsible for the
        production of aldosterone in humans.
- term:
    id: GO:0035865
    label: cellular response to potassium ion
  evidence_type: IEP
  original_reference_id: PMID:19342457
  qualifier: involved_in
  review:
    summary: >-
      Expression-pattern (IEP) evidence that CYP11B2 transcription responds to
      extracellular potassium (K+), via T-type calcium channel (Cav3.2/CACNA1H)
      signaling and NRSF/NRSE regulation, increasing aldosterone output.
    action: KEEP_AS_NON_CORE
    reason: >-
      Reflects transcriptional/physiological regulation of the gene by K+ rather
      than a molecular activity of the enzyme; real but peripheral to core
      function.
    supported_by:
    - reference_id: PMID:19342457
      supporting_text: >-
        NRSF/NRSE is also involved in
        angiotensin II- and K(+)-stimulated augmentation of CYP11B2 and CYP11B1 gene
        transcription.
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:19342457
  qualifier: involved_in
  review:
    summary: >-
      Mutation/perturbation (IMP) evidence: modulating CYP11B2 expression (via
      NRSF inhibition) changes aldosterone secretion in human adrenocortical
      cells, supporting its role in aldosterone biosynthesis.
    action: ACCEPT
    reason: >-
      Core BP; consistent with the enzyme's defining function.
    supported_by:
    - reference_id: PMID:19342457
      supporting_text: >-
        increased human CYP11B2 and CYP11B1 mRNA
        expression, leading to aldosterone and cortisol secretion in human
        adrenocortical (H295R) cells
- term:
    id: GO:0032870
    label: cellular response to hormone stimulus
  evidence_type: IEP
  original_reference_id: PMID:19342457
  qualifier: involved_in
  review:
    summary: >-
      Expression-pattern (IEP) evidence that CYP11B2 transcription responds to
      hormonal stimulation (e.g. angiotensin II), consistent with regulation of
      aldosterone production.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/physiological response term, not a molecular function of the
      protein; peripheral to core enzymatic role.
    supported_by:
    - reference_id: PMID:19342457
      supporting_text: >-
        NRSF/NRSE is also involved in
        angiotensin II- and K(+)-stimulated augmentation of CYP11B2 and CYP11B1 gene
        transcription.
- term:
    id: GO:0034651
    label: cortisol biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:19342457
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation to cortisol biosynthesis from a study where NRSF inhibition
      increased both CYP11B2 and CYP11B1 expression and both aldosterone and
      cortisol secretion in H295R cells. Physiological cortisol production is
      driven by the paralog CYP11B1, not CYP11B2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The cortisol readout in this experiment reflects the co-induced CYP11B1 (and
      possibly low-level in-vitro CYP11B2 activity), not the physiological role of
      CYP11B2. This is contradicted by the BHF-UCL NOT|involved_in cortisol
      biosynthesis annotation and by the CYP11B1/CYP11B2 division of labor, so it
      is flagged as an over-annotation rather than a core function.
    supported_by:
    - reference_id: PMID:19342457
      supporting_text: >-
        Aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) regulate
        aldosterone and cortisol production, respectively.
- term:
    id: GO:0034651
    label: cortisol biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:9703385
  qualifier: involved_in
  negated: true
  review:
    summary: >-
      NOT|involved_in cortisol biosynthetic process. In CMO-deficiency patients,
      cortisol and its precursors are in the normal range despite defective
      aldosterone synthesis, indicating CYP11B2 is not required for cortisol
      production (that is the role of CYP11B1).
    action: ACCEPT
    reason: >-
      Correct negation: CYP11B2 loss does not impair cortisol biosynthesis,
      consistent with the CYP11B1/CYP11B2 division of labor. This negated
      annotation is well supported and appropriately curated.
    supported_by:
    - reference_id: PMID:9703385
      supporting_text: >-
        Plasma corticosterone and 11-deoxycorticosterone were elevated in both
        patients, whereas cortisol and its precursors were in the normal range.
- term:
    id: GO:0002017
    label: regulation of blood volume by renal aldosterone
  evidence_type: IMP
  original_reference_id: PMID:14614232
  qualifier: involved_in
  review:
    summary: >-
      IMP from CMO-II deficiency patients: CYP11B2 loss-of-function reduces
      aldosterone, causing salt-wasting and disturbed volume/electrolyte balance,
      linking the enzyme to aldosterone-mediated regulation of blood volume.
    action: KEEP_AS_NON_CORE
    reason: >-
      A downstream physiological consequence of aldosterone production, not the
      enzyme's molecular core function; retained as a non-core organismal role.
    supported_by:
    - reference_id: PMID:14614232
      supporting_text: >-
        Japanese patients newly diagnosed
        with CMO II deficiency
- term:
    id: GO:0003091
    label: renal water homeostasis
  evidence_type: IC
  original_reference_id: PMID:2256920
  qualifier: involved_in
  review:
    summary: >-
      Curator inference (IC, from aldosterone biosynthetic process) that CYP11B2,
      by producing aldosterone, contributes to renal water homeostasis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Downstream physiological consequence of aldosterone action on the kidney;
      not the enzyme's molecular core function.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: IDA
  original_reference_id: PMID:1741400
  qualifier: enables
  review:
    summary: >-
      Direct assay: CYP11B2 (P-450C18) expressed in COS-7 cells exhibits steroid
      11-beta-hydroxylase activity in addition to 18-hydroxylase activity.
    action: ACCEPT
    reason: >-
      Core molecular function supported by direct heterologous-expression assay.
    supported_by:
    - reference_id: PMID:1741400
      supporting_text: >-
        exhibits steroid 18-hydroxylase activity to catalyze
        the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11
        beta-hydroxylase activity as well.
- term:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  evidence_type: IDA
  original_reference_id: PMID:2256920
  qualifier: enables
  review:
    summary: >-
      Direct assay: P-450aldo (CYP11B2) expressed in COS-7 cells forms
      corticosterone from 11-deoxycorticosterone (11-beta-hydroxylation).
    action: ACCEPT
    reason: >-
      Core molecular function supported by direct heterologous-expression assay.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        both enzymes catalyze
        the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using
        11-deoxycorticosterone as a substrate
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:1741400
  qualifier: located_in
  review:
    summary: >-
      IDA mitochondrion localization from expression studies of CYP11B2, a
      mitochondrial P450. Consistent with the curated inner-membrane location.
    action: ACCEPT
    reason: >-
      Correct localization; less specific than the mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IC
  original_reference_id: PMID:2256920
  qualifier: located_in
  review:
    summary: >-
      Curator inference (IC, from steroid 11-beta-monooxygenase activity) placing
      CYP11B2 at the mitochondrial inner membrane, where mitochondrial P450s and
      the adrenodoxin electron system operate.
    action: ACCEPT
    reason: >-
      Correct core CC; consistent with UniProt subcellular location and Reactome.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0006700
    label: C21-steroid hormone biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:2256920
  qualifier: involved_in
  review:
    summary: >-
      IDA to C21-steroid hormone biosynthesis: CYP11B2 synthesizes aldosterone (a
      C21 corticosteroid) from 11-deoxycorticosterone via corticosterone and
      18-hydroxycorticosterone.
    action: ACCEPT
    reason: >-
      Correct broader biosynthetic BP; aldosterone is a C21 steroid hormone.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IC
  original_reference_id: PMID:2256920
  qualifier: enables
  review:
    summary: >-
      Curator inference (IC, from steroid 11-beta-monooxygenase activity) that
      CYP11B2 binds heme, as expected for a cytochrome P450.
    action: ACCEPT
    reason: >-
      Correct; heme is the catalytic cofactor, later confirmed structurally
      (PMID:23322723). Secondary/enabling MF.
    supported_by:
    - reference_id: PMID:23322723
      supporting_text: >-
        we present the crystal structures of human
        aldosterone synthase in complex with a substrate deoxycorticosterone
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:1741400
  qualifier: involved_in
  review:
    summary: >-
      Direct assay: CYP11B2 catalyzes the synthesis of aldosterone (via its
      18-hydroxylase/18-oxidase activity), unlike CYP11B1 which cannot.
    action: ACCEPT
    reason: >-
      Core BP directly demonstrated by heterologous expression.
    supported_by:
    - reference_id: PMID:1741400
      supporting_text: >-
        exhibits steroid 18-hydroxylase activity to catalyze
        the synthesis of aldosterone and 18-oxocortisol
- term:
    id: GO:0032342
    label: aldosterone biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:2256920
  qualifier: involved_in
  review:
    summary: >-
      Direct assay: P-450aldo (CYP11B2) preferentially converts
      11-deoxycorticosterone to aldosterone, unlike P-450(11)beta (CYP11B1).
    action: ACCEPT
    reason: >-
      Core BP directly demonstrated; this study distinguishes CYP11B2 from CYP11B1
      by the aldosterone-forming capacity.
    supported_by:
    - reference_id: PMID:2256920
      supporting_text: >-
        P-450aldo preferentially catalyzes the conversion of
        11-deoxycorticosterone to aldosterone via corticosterone and
        18-hydroxycorticosterone
- term:
    id: GO:0055075
    label: potassium ion homeostasis
  evidence_type: IMP
  original_reference_id: PMID:9838244
  qualifier: involved_in
  review:
    summary: >-
      IMP from a CMO-II deficiency patient with homozygous R173 deletion: loss of
      aldosterone synthase activity causes elevated plasma potassium (and low
      sodium), linking CYP11B2 to potassium homeostasis via aldosterone.
    action: KEEP_AS_NON_CORE
    reason: >-
      Downstream physiological consequence of aldosterone deficiency, not the
      enzyme's molecular core function.
    supported_by:
    - reference_id: PMID:9838244
      supporting_text: >-
        Important laboratory findings were low plasma
        sodium and elevated potassium and renin.
- term:
    id: GO:0055078
    label: sodium ion homeostasis
  evidence_type: IMP
  original_reference_id: PMID:9838244
  qualifier: involved_in
  review:
    summary: >-
      IMP from a CMO-II deficiency patient: loss of aldosterone synthase causes
      salt-wasting with low plasma sodium, linking CYP11B2 to sodium homeostasis
      via aldosterone.
    action: KEEP_AS_NON_CORE
    reason: >-
      Downstream physiological consequence of aldosterone deficiency, not the
      enzyme's molecular core function.
    supported_by:
    - reference_id: PMID:9838244
      supporting_text: >-
        Salt wasting was caused by an enzymatic
        defect in the terminal aldosterone biosynthesis.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:2256920
  qualifier: located_in
  review:
    summary: >-
      IDA mitochondrion localization from expression studies of P-450aldo
      (CYP11B2), a mitochondrial cytochrome P450.
    action: ACCEPT
    reason: >-
      Correct localization; less specific than the mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP11B2/CYP11B2-uniprot.txt
      supporting_text: Mitochondrion inner membrane
core_functions:
- description: >-
    Corticosterone 18-monooxygenase / aldosterone synthase activity (EC 1.14.15.5):
    18-hydroxylation of corticosterone and subsequent 18-oxidation of
    18-hydroxycorticosterone to aldosterone. This 18-oxidase capability is the
    feature that distinguishes CYP11B2 from the near-identical CYP11B1.
  molecular_function:
    id: GO:0047783
    label: corticosterone 18-monooxygenase activity
  directly_involved_in:
  - id: GO:0032342
    label: aldosterone biosynthetic process
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: PMID:23322723
    supporting_text: >-
      most of the divergent residues that confer additional 18-oxidase activity
      of aldosterone synthase are located in the
- description: >-
    Steroid 11-beta-monooxygenase activity (EC 1.14.15.4): 11-beta-hydroxylation of
    11-deoxycorticosterone to corticosterone, the first of the three sequential
    reactions leading to aldosterone.
  molecular_function:
    id: GO:0004507
    label: steroid 11-beta-monooxygenase activity
  directly_involved_in:
  - id: GO:0032342
    label: aldosterone biosynthetic process
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: PMID:23322723
    supporting_text: >-
      explains the high 11β-hydroxylase activity of aldosterone synthase toward
      both gluco- and mineralocorticoid formation
- description: >-
    Heme binding: CYP11B2 is a heme-thiolate cytochrome P450 whose catalytic heme
    iron (axial cysteine ligand) supports its monooxygenase chemistry. Secondary
    cofactor-binding function underlying the core catalytic activities.
  molecular_function:
    id: GO:0020037
    label: heme binding
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: PMID:23322723
    supporting_text: >-
      we present the crystal structures of human
      aldosterone synthase in complex with a substrate deoxycorticosterone
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/CYP11B2/CYP11B2-uniprot.txt
  title: UniProtKB entry P19099 (C11B2_HUMAN), Cytochrome P450 11B2, mitochondrial
  findings: []
- id: PMID:14614232
  title: A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene
    inherited in Japanese patients with congenital hypoaldosteronism.
  findings: []
- id: PMID:1741400
  title: Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis
    of glucocorticoids and mineralocorticoids in humans.
  findings: []
- id: PMID:19342457
  title: Regulation of aldosterone and cortisol production by the transcriptional
    repressor neuron restrictive silencer factor.
  findings: []
- id: PMID:2256920
  title: Cloning and expression of a cDNA for human cytochrome P-450aldo as related
    to primary aldosteronism.
  findings: []
- id: PMID:23322723
  title: Structural insights into aldosterone synthase substrate specificity and targeted
    inhibition.
  findings: []
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
- id: PMID:9703385
  title: Molecular genetic study in two patients with congenital hypoaldosteronism
    (types I and II) in relation to previously published hormonal studies.
  findings: []
- id: PMID:9838244
  title: Homozygous deletion of arginine-173 in the CYP11B2 gene in a girl with congenital
    hypoaldosteronism. Corticosterone methyloxidase deficiency type II.
  findings: []
- id: Reactome:R-HSA-193965
  title: CYP11B2 oxidises 18HCORST to ALDO
  findings: []
- id: Reactome:R-HSA-193993
  title: Mineralocorticoid biosynthesis
  findings: []
- id: Reactome:R-HSA-193995
  title: CYP11B2 18-hydroxylates CORST to 18HCORST
  findings: []
- id: Reactome:R-HSA-194017
  title: CYP11B2 oxidises 11DCORST to CORST
  findings: []
- id: Reactome:R-HSA-211976
  title: Endogenous sterols
  findings: []
- id: Reactome:R-HSA-5600598
  title: Defective CYP11B2 does not oxidise 11DCORST
  findings: []
- id: Reactome:R-HSA-6785244
  title: Defective CYP11B2 does not oxidise 18HCORST
  findings: []
- id: Reactome:R-HSA-6785245
  title: Defective CYP11B2 does not oxidise CORST
  findings: []

Gene Description

Existing Annotations Review

Core Functions

Corticosterone 18-monooxygenase / aldosterone synthase activity (EC 1.14.15.5): 18-hydroxylation of corticosterone and subsequent 18-oxidation of 18-hydroxycorticosterone to aldosterone. This 18-oxidase capability is the feature that distinguishes CYP11B2 from the near-identical CYP11B1.

Steroid 11-beta-monooxygenase activity (EC 1.14.15.4): 11-beta-hydroxylation of 11-deoxycorticosterone to corticosterone, the first of the three sequential reactions leading to aldosterone.

Heme binding: CYP11B2 is a heme-thiolate cytochrome P450 whose catalytic heme iron (axial cysteine ligand) supports its monooxygenase chemistry. Secondary cofactor-binding function underlying the core catalytic activities.

References

📚 Additional Documentation

Notes

CYP11B2 (P19099) review notes

Identity / core biology

Localization

Disease

Curation decisions summary

📄 View Raw YAML