CYP11B1 is a heme-containing cytochrome P450 at the mitochondrial inner membrane of adrenal cortical cells. It catalyzes 11-beta hydroxylation of 11-deoxycortisol to cortisol and of deoxycorticosterone to corticosterone, using electrons delivered through the mitochondrial adrenodoxin system. It also hydroxylates androgen substrates and has secondary steroid 18-hydroxylase activity. Unlike human CYP11B2, it lacks effective terminal 18-oxidation needed to produce aldosterone. CYP11B1 is a major cortisol-producing enzyme in the zona fasciculata and reticularis; loss of activity causes congenital adrenal hyperplasia with deficient cortisol synthesis, androgen excess and frequently hypertension associated with accumulated steroid precursors.
| 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: CYP11B1 also metabolizes cortisol by secondary 18-hydroxylation. Reason: In addition to making cortisol, CYP11B1-transfected cells convert supplied cortisol to 18-hydroxycortisol. The metabolic term therefore captures secondary substrate chemistry beyond the independently asserted cortisol biosynthesis; it is not retained merely as a redundant broad parent. Supporting Evidence: PMID:15356073 Both enzymes could synthesize 18-OHF from cortisol, but only AS could synthesize 18-oxoF. |
| 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 SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0032342 aldosterone biosynthetic process | IBA GO_REF:0000033 | UNDECIDED | Summary: The scope of broad CYP11B1 participation in aldosterone biosynthesis remains unresolved. Reason: Human CYP11B1 lacks the terminal 18-oxidase activity and does not complete aldosterone synthesis, but it does catalyze upstream formation of corticosterone and some 18-hydroxysteroids. Failure to make the final product alone does not disprove involvement in an earlier pathway step. The NRSF experiment changes both CYP11B genes and steroid outputs together; it does not isolate physiological CYP11B1 contribution to aldosterone flux. Retain uncertainty about this broad process rather than equate it with aldosterone-synthase activity. CYP11B1 is not assigned the terminal oxidation core function. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001547324 UNRESOLVED Current QuickGO identifies this ancestral source. Terminal-oxidase loss does not by itself resolve broad pathway participation; no new family-tree node-placement assertion is made. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. |
| 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 | KEEP AS NON CORE | Summary: Retain the existing broad sterol-derived pathway context conservatively. Reason: These process terms include pathways, not only direct binding or conversion of cholesterol. Reactome Endogenous sterols includes steroid-hormone synthesis among cholesterol-utilization pathways, and CYP11B1 catalyzes downstream cortisol-producing chemistry. This does not assert cholesterol side-chain cleavage or cholesterol homeostatic regulation. The broad pathway boundary remains a convention question; substrate differences alone do not refute the ancestral assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001547321 SUPPORTS TRANSFER Current QuickGO identifies the same ancestral source as the separately reconstructed CYP11B2 branch. Retain broad pathway context without treating CYP11A1 descendant sources as a pairwise functional transfer. Supporting Evidence: Reactome:R-HSA-211976 used in steroid hormone synthesis PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol. |
| 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: Retain the specific phylogenetic assignment as secondary C18 hydroxylation. The inspected human study discusses 18-hydroxycorticosterone formation and directly demonstrates C18 hydroxylation of cortisol; the curated UniProt regioselectivity statement supplies corroborating homolog evidence. This does not equate 18-hydroxylation with the terminal 18-oxidase activity, nor claim the cortisol assay itself measured corticosterone turnover. Supporting Evidence: PMID:15356073 11Ξ²-hydroxylase is probably also the source of many circulating 18-hydroxysteroids, for example, 18-OH-DOC, 18-hydroxycorticosterone and 18-hydroxyprogesterone, in normal subjects. file:human/CYP11B1/CYP11B1-uniprot.txt Steroid 11beta, 18- and CC 19-hydroxylase with preferred regioselectivity at 11beta, then 18, and CC lastly 19 (By similarity). |
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | MODIFY | Summary: Specify the demonstrated steroid hydroxylase reactions. Reason: The enzyme has independently supported 11-beta hydroxylation and secondary C18 hydroxylation. Both activities refine this broad catalytic term; C18 hydroxylation is distinct from the terminal oxidation required for aldosterone formation. Proposed replacements: steroid 11-beta-monooxygenase activity corticosterone 18-monooxygenase activity Supporting Evidence: PMID:18215163 The results clearly demonstrate that the enzyme is capable of hydroxylating its substrates at position 11-beta. PMID:15356073 Both enzymes could synthesize 18-OHF from cortisol, but only AS could synthesize 18-oxoF. |
| 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: CYP11B1 has supported mitochondrion localization, retained separately from its subcompartment annotations. Reason: The electronic organelle assignment is consistent with the curated mitochondrial P450 location. The UniProt inner-membrane statement is similarity-based and supports the organelle without implying new target-specific topology experiments. Keep the separately annotated membrane location alongside mitochondrion. Under the root-organelle policy, retain this supported organelle assertion and its separate subcompartment claims. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt SUBCELLULAR LOCATION: 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 SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0016125 sterol metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the existing broad sterol-derived pathway context conservatively. Reason: These process terms include pathways, not only direct binding or conversion of cholesterol. Reactome Endogenous sterols includes steroid-hormone synthesis among cholesterol-utilization pathways, and CYP11B1 catalyzes downstream cortisol-producing chemistry. This does not assert cholesterol side-chain cleavage or cholesterol homeostatic regulation. The broad pathway boundary remains a convention question; substrate differences alone do not refute the ancestral assertion. Supporting Evidence: Reactome:R-HSA-211976 used in steroid hormone synthesis PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol. |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MODIFY | Summary: Specify the demonstrated steroid hydroxylase reactions. Reason: The enzyme has independently supported 11-beta hydroxylation and secondary C18 hydroxylation. Both activities refine this broad catalytic term; C18 hydroxylation is distinct from the terminal oxidation required for aldosterone formation. Proposed replacements: steroid 11-beta-monooxygenase activity corticosterone 18-monooxygenase activity Supporting Evidence: PMID:18215163 The results clearly demonstrate that the enzyme is capable of hydroxylating its substrates at position 11-beta. PMID:15356073 Both enzymes could synthesize 18-OHF from cortisol, but only AS could synthesize 18-oxoF. |
| 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 | UNDECIDED | Summary: The scope of broad CYP11B1 participation in aldosterone biosynthesis remains unresolved. Reason: Human CYP11B1 lacks the terminal 18-oxidase activity and does not complete aldosterone synthesis, but it does catalyze upstream formation of corticosterone and some 18-hydroxysteroids. Failure to make the final product alone does not disprove involvement in an earlier pathway step. The NRSF experiment changes both CYP11B genes and steroid outputs together; it does not isolate physiological CYP11B1 contribution to aldosterone flux. Retain uncertainty about this broad process rather than equate it with aldosterone-synthase activity. CYP11B1 is not assigned the terminal oxidation core function. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. |
| 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: Retain the existing broad sterol-derived pathway context conservatively. Reason: These process terms include pathways, not only direct binding or conversion of cholesterol. Reactome Endogenous sterols includes steroid-hormone synthesis among cholesterol-utilization pathways, and CYP11B1 catalyzes downstream cortisol-producing chemistry. This does not assert cholesterol side-chain cleavage or cholesterol homeostatic regulation. The broad pathway boundary remains a convention question; substrate differences alone do not refute the ancestral assertion. Supporting Evidence: Reactome:R-HSA-211976 used in steroid hormone synthesis PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol. |
| 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 SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: CYP11B1 has supported mitochondrion localization, retained separately from its subcompartment annotations. Reason: Retain the MitoCoP-derived mitochondrial assignment together with curated target mitochondrial localization. The target-specific experimental identification fields were not independently re-inspected here, so inclusion is not promoted to a new mass-spectrometry detection claim or membrane-topology assay. Under the root-organelle policy, retain this supported organelle assertion and its separate subcompartment claims. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| 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 SUBCELLULAR LOCATION: 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... | UNDECIDED | Summary: The scope of broad CYP11B1 participation in aldosterone biosynthesis remains unresolved. Reason: Human CYP11B1 lacks the terminal 18-oxidase activity and does not complete aldosterone synthesis, but it does catalyze upstream formation of corticosterone and some 18-hydroxysteroids. Failure to make the final product alone does not disprove involvement in an earlier pathway step. The NRSF experiment changes both CYP11B genes and steroid outputs together; it does not isolate physiological CYP11B1 contribution to aldosterone flux. Retain uncertainty about this broad process rather than equate it with aldosterone-synthase activity. CYP11B1 is not assigned the terminal oxidation core function. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. |
| GO:0032870 cellular response to hormone stimulus | IEP PMID:19342457 Regulation of aldosterone and cortisol production by the tra... | MODIFY | Summary: Specify the measured peptide-hormone response. Reason: The cited experiment explicitly describes angiotensin II-responsive CYP11B1 transcription; the peptide-hormone response already present is the supported specific refinement. Proposed replacements: cellular response to peptide hormone stimulus 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----His) associated with stero... | 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 SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0006700 C21-steroid hormone biosynthetic process | IDA PMID:2256920 Cloning and expression of a cDNA for human cytochrome P-450a... | MODIFY | Summary: Specify glucocorticoid biosynthesis within C21-steroid synthesis. Reason: CYP11B1 produces both cortisol and corticosterone. The glucocorticoid process captures both products and is more precise than the general C21-steroid hormone term. Proposed replacements: glucocorticoid biosynthetic process Supporting Evidence: PMID:18215163 The human 11beta-hydroxylase (hCYP11B1) is responsible for the conversion of 11-deoxycortisol into the major mammalian glucocorticoid, cortisol. PMID:18215163 The results clearly demonstrate that the enzyme is capable of hydroxylating its substrates at position 11-beta. |
| GO:0006955 immune response | TAS PMID:12452430 The human steroid hydroxylases CYP1B1 and CYP11B2. | UNDECIDED | Summary: The specific physiological process could not be verified from the accessible cited source. Reason: The cited review abstract establishes cortisol synthesis but does not resolve the scope of the immune-response annotation. Cortisol-dependent immune effects are plausible, but the full cited discussion was not accessible; an indirect mechanism alone is not sufficient reason to reject an existing physiological-process annotation. Supporting Evidence: |
| GO:0008217 regulation of blood pressure | IMP PMID:2022736 A mutation in CYP11B1 (Arg-448----His) associated with stero... | 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... | UNDECIDED | Summary: The scope of broad CYP11B1 participation in aldosterone biosynthesis remains unresolved. Reason: Human CYP11B1 lacks the terminal 18-oxidase activity and does not complete aldosterone synthesis, but it does catalyze upstream formation of corticosterone and some 18-hydroxysteroids. Failure to make the final product alone does not disprove involvement in an earlier pathway step. The NRSF experiment changes both CYP11B genes and steroid outputs together; it does not isolate physiological CYP11B1 contribution to aldosterone flux. Retain uncertainty about this broad process rather than equate it with aldosterone-synthase activity. CYP11B1 is not assigned the terminal oxidation core function. Supporting Evidence: PMID:2256920 both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. |
| GO:0004507 steroid 11-beta-monooxygenase activity | IMP PMID:2022736 A mutation in CYP11B1 (Arg-448----His) associated with stero... | 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: CYP11B1 has supported mitochondrion localization, retained separately from its subcompartment annotations. Reason: The original curated direct-assay location agrees with the independently curated mitochondrial compartment. The accessible 1990 abstract describes expression and steroid conversion, not the detailed localization assay; those source methods are not claimed as newly inspected. The supported root location remains valid independently of membrane-specific detail. Under the root-organelle policy, retain this supported organelle assertion and its separate subcompartment claims. Supporting Evidence: file:human/CYP11B1/CYP11B1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0042593 glucose homeostasis | TAS PMID:16114325 [Hypoglycemia due to a disorder of adrenal cortical regulati... | UNDECIDED | Summary: The specific physiological process could not be verified from the accessible cited source. Reason: The cited 1978 French report has no accessible abstract or full text. A title mentioning hypoglycemia does not establish the CYP11B1-specific mechanism; leave this source-specific physiological claim unresolved. Supporting Evidence: |
| 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 SUBCELLULAR LOCATION: Mitochondrion inner membrane |
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