Cyp11a1.1, historically called Cyp11a1, is a mitochondrial cholesterol side-chain-cleavage enzyme that supplies pregnenolone. In zebrafish it is associated with maternal and early extraembryonic steroid production and is expressed mainly in gonads in adults. Pregnenolone supports microtubule-dependent embryonic movements; morpholino and stable-mutant phenotypes differ, so an unconditional requirement for this paralog alone is not established. The tandem duplicate Cyp11a1.2, historically Cyp11a2, has the better established interrenal steroidogenic role.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad P450 oxidoreductase function can be specified as cholesterol side-chain cleavage. Reason: Curated RuleBase RU364077 assigns the substrate-specific reaction; zebrafish gene-function studies corroborate pregnenolone production or rescue. Refine the true broad molecular function to GO:0008386, without treating all CYP-family members as steroidogenic. Proposed replacements: cholesterol monooxygenase (side-chain-cleaving) activity Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: The CYP11A enzyme uses a catalytic heme iron center. Reason: PIRSR/RuleBase cofactor assignments and the conserved cytochrome P450 catalytic architecture support this core cofactor property. This is comparative evidence, not a metal-occupancy measurement on the zebrafish protein; it does not imply a ferredoxin iron-sulfur cluster within CYP11A itself. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | MODIFY | Summary: The mitochondrial location can be refined to the inner membrane. Reason: Use the independently curated RuleBase inner-membrane localization, already represented among the annotations. This is a comparative localization inference; no native zebrafish microscopy result is claimed. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Localizes to the matrix side of the mitochondrion inner membrane. |
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Cyp11a1 is assigned to the matrix-facing inner mitochondrial membrane. Reason: The curated RuleBase compartment statement supports the inherited CYP11A localization. No evidence of retargeting was identified for this protein; retention is not based only on the annotation under review. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Localizes to the matrix side of the mitochondrion inner membrane. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Cyp11a1 is assigned to the matrix-facing inner mitochondrial membrane. Reason: The curated RuleBase compartment statement supports the inherited CYP11A localization. No evidence of retargeting was identified for this protein; retention is not based only on the annotation under review. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Localizes to the matrix side of the mitochondrion inner membrane. |
| GO:0006700 C21-steroid hormone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Pregnenolone synthesis is a directly catalyzed C21-steroid biosynthetic step. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0006700 C21-steroid hormone biosynthetic process | IMP PMID:16437115 Pregnenolone stabilizes microtubules and promotes zebrafish ... | ACCEPT | Summary: Pregnenolone synthesis is a directly catalyzed C21-steroid biosynthetic step. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0006704 glucocorticoid biosynthetic process | IBA GO_REF:0000033 | UNDECIDED | Summary: The adrenal-equivalent glucocorticoid role is not resolved for this paralog. Reason: The PAINT-inherited term is biologically plausible for a CYP11A enzyme, but PMID:23671259 specifically reassigns maintained interrenal steroidogenesis to cyp11a2/current cyp11a1.2 and distinguishes cyp11a1/current cyp11a1.1 expression. Conserved cholesterol cleavage alone cannot settle target tissue deployment. This is uncertainty about subfunctionalization, not a donor-count objection or proof of catalytic loss. Propagation Review Root cause: UNRESOLVED Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN001547321 UNRESOLVED Cached PAINT identifies an IBD for this process at this node. The target retains CYP11A chemistry, but paralog-specific expression evidence leaves tissue/process deployment unresolved; no precise ancestral misplacement or function loss is asserted. Supporting Evidence: PMID:23671259 cyp11a2 is expressed in adult steroidogenic tissues, such as the interrenal, gonads, and brain. In contrast, cyp11a1 was mainly restricted to the gonads. PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0008203 cholesterol metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Cholesterol is directly metabolized by the CYP11A reaction. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0008207 C21-steroid hormone metabolic process | IEA GO_REF:0000041 | MODIFY | Summary: C21-steroid metabolism is specifically biosynthetic at this reaction. Reason: Refine the metabolic parent to the existing C21-steroid hormone biosynthetic process, reflecting pregnenolone production rather than hormone degradation. Proposed replacements: C21-steroid hormone biosynthetic process Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0008386 cholesterol monooxygenase (side-chain-cleaving) activity | IC PMID:16437115 Pregnenolone stabilizes microtubules and promotes zebrafish ... | ACCEPT | Summary: The protein catalyzes cholesterol side-chain cleavage to pregnenolone. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0008386 cholesterol monooxygenase (side-chain-cleaving) activity | IEA GO_REF:0000003 | ACCEPT | Summary: The protein catalyzes cholesterol side-chain cleavage to pregnenolone. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0008386 cholesterol monooxygenase (side-chain-cleaving) activity | ISS GO_REF:0000024 | ACCEPT | Summary: The protein catalyzes cholesterol side-chain cleavage to pregnenolone. Reason: PMID:16437115 links this historical cyp11a1 gene to pregnenolone production and rescue; its official current symbol is cyp11a1.1. The conserved catalytic assignment does not establish the same interrenal role as its tandem duplicate. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MODIFY | Summary: The broad P450 oxidoreductase function can be specified as cholesterol side-chain cleavage. Reason: Curated RuleBase RU364077 assigns the substrate-specific reaction; zebrafish gene-function studies corroborate pregnenolone production or rescue. Refine the true broad molecular function to GO:0008386, without treating all CYP-family members as steroidogenic. Proposed replacements: cholesterol monooxygenase (side-chain-cleaving) activity Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: The CYP11A enzyme uses a catalytic heme iron center. Reason: PIRSR/RuleBase cofactor assignments and the conserved cytochrome P450 catalytic architecture support this core cofactor property. This is comparative evidence, not a metal-occupancy measurement on the zebrafish protein; it does not imply a ferredoxin iron-sulfur cluster within CYP11A itself. Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone |
| GO:0031116 positive regulation of microtubule polymerization | IGI PMID:23955365 Pregnenolone activates CLIP-170 to promote microtubule growt... | KEEP AS NON CORE | Summary: Pregnenolone production supports microtubule polymerization during embryonic development. Reason: Retain the existing developmental regulation claim as a product-mediated effect, not direct microtubule binding by CYP11A. PMID:16437115 reports reduced polymerized microtubules after cyp11a1 knockdown and pregnenolone rescue; PMID:23955365 identifies CLIP-170 as the downstream pregnenolone effector. Stable knockout and morphant phenotypes differ (PMID:36332486), so this is not an unconditional requirement for this paralog. Supporting Evidence: PMID:16437115 the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. PMID:36332486 Both homozygous cyp11a1 knockout lines appeared normal. PMID:23955365 P5 activates CLIP-170 to promote microtubule polymerization and cell migration. |
| GO:0031116 positive regulation of microtubule polymerization | IMP PMID:16437115 Pregnenolone stabilizes microtubules and promotes zebrafish ... | KEEP AS NON CORE | Summary: Pregnenolone production supports microtubule polymerization during embryonic development. Reason: Retain the existing developmental regulation claim as a product-mediated effect, not direct microtubule binding by CYP11A. PMID:16437115 reports reduced polymerized microtubules after cyp11a1 knockdown and pregnenolone rescue; PMID:23955365 identifies CLIP-170 as the downstream pregnenolone effector. Stable knockout and morphant phenotypes differ (PMID:36332486), so this is not an unconditional requirement for this paralog. Supporting Evidence: PMID:16437115 the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. PMID:36332486 Both homozygous cyp11a1 knockout lines appeared normal. PMID:23955365 P5 activates CLIP-170 to promote microtubule polymerization and cell migration. |
| GO:0031116 positive regulation of microtubule polymerization | IMP PMID:23955365 Pregnenolone activates CLIP-170 to promote microtubule growt... | KEEP AS NON CORE | Summary: Pregnenolone production supports microtubule polymerization during embryonic development. Reason: Retain the existing developmental regulation claim as a product-mediated effect, not direct microtubule binding by CYP11A. PMID:16437115 reports reduced polymerized microtubules after cyp11a1 knockdown and pregnenolone rescue; PMID:23955365 identifies CLIP-170 as the downstream pregnenolone effector. Stable knockout and morphant phenotypes differ (PMID:36332486), so this is not an unconditional requirement for this paralog. Supporting Evidence: PMID:16437115 the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. PMID:36332486 Both homozygous cyp11a1 knockout lines appeared normal. PMID:23955365 P5 activates CLIP-170 to promote microtubule polymerization and cell migration. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MODIFY | Summary: The mitochondrial location can be refined to the inner membrane. Reason: Use the independently curated RuleBase inner-membrane localization, already represented among the annotations. This is a comparative localization inference; no native zebrafish microscopy result is claimed. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:DANRE/cyp11a1.1/cyp11a1.1-uniprot.txt Localizes to the matrix side of the mitochondrion inner membrane. |
| GO:0034650 cortisol metabolic process | IBA GO_REF:0000033 | UNDECIDED | Summary: The adrenal-equivalent glucocorticoid role is not resolved for this paralog. Reason: The PAINT-inherited term is biologically plausible for a CYP11A enzyme, but PMID:23671259 specifically reassigns maintained interrenal steroidogenesis to cyp11a2/current cyp11a1.2 and distinguishes cyp11a1/current cyp11a1.1 expression. Conserved cholesterol cleavage alone cannot settle target tissue deployment. This is uncertainty about subfunctionalization, not a donor-count objection or proof of catalytic loss. Propagation Review Root cause: UNRESOLVED Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN001547321 UNRESOLVED Cached PAINT identifies an IBD for this process at this node. The target retains CYP11A chemistry, but paralog-specific expression evidence leaves tissue/process deployment unresolved; no precise ancestral misplacement or function loss is asserted. Supporting Evidence: PMID:23671259 cyp11a2 is expressed in adult steroidogenic tissues, such as the interrenal, gonads, and brain. In contrast, cyp11a1 was mainly restricted to the gonads. PMID:16437115 pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc) |
| GO:0048545 response to steroid hormone | IEP PMID:28265462 Fine selection of up-regulated genes during ovulation by in ... | KEEP AS NON CORE | Summary: Ovarian cyp11a1.1 expression responds to steroid treatment. Reason: PMID:28265462 profiles treated zebrafish ovaries and identifies NM_152953, matching this gene, among steroid-responsive transcripts. Retain the original expression-response context without converting differential expression into evidence of a new enzymatic function or steroid-receptor activity. Supporting Evidence: PMID:28265462 cyp11a1NM_152953Danio rerio cytochrome P450 |
| GO:0061371 determination of heart left/right asymmetry | IMP PMID:31075101 Pathway-specific protein domains are predictive for human di... | UNDECIDED | Summary: A heart-asymmetry phenotype is reported, but the source-specific target mapping needs resolution. Reason: The full text of PMID:31075101 tests a gene rendered as cypna1 and reports abnormal heart asymmetry after morpholino treatment. The curated association maps to this cyp11a1.1 record, but the assayed sequence/construct mapping was not independently resolved here. Do not call the annotation a wrong-gene error or infer a cardiac mechanism solely from the title or phenotype. Supporting Evidence: PMID:31075101 the tram1, cypna1, and slc22a2 groups PMID:31075101 embryos injected with MOs related to CAD genes exhibited either no asymmetry or reversed V and A orientation |
| GO:0071375 cellular response to peptide hormone stimulus | IBA GO_REF:0000033 | UNDECIDED | Summary: A peptide-hormone response role remains uncertain for the developmentally specialized paralog. Reason: The term is phylogenetically inherited, but the examined target literature establishes embryonic/gonadal deployment rather than a specific peptide-hormone-induced cellular response. The paralog-specific interrenal distinction makes a generic ACTH-effector rationale insufficient. No claim of lost catalytic capacity is made. Propagation Review Root cause: UNRESOLVED Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN001547321 UNRESOLVED Cached PAINT identifies an IBD for this process at this node. The target retains CYP11A chemistry, but paralog-specific expression evidence leaves tissue/process deployment unresolved; no precise ancestral misplacement or function loss is asserted. Supporting Evidence: PMID:23671259 cyp11a2 is expressed in adult steroidogenic tissues, such as the interrenal, gonads, and brain. In contrast, cyp11a1 was mainly restricted to the gonads. |
| GO:0090504 epiboly | IMP PMID:23671259 Redefining the initiation and maintenance of zebrafish inter... | KEEP AS NON CORE | Summary: The original morpholino study links cyp11a1.1-dependent pregnenolone production to epiboly. Reason: PMID:23671259 confirms abnormal gastrulation in historical cyp11a1 morphants, consistent with PMID:16437115 rescue experiments. Retain this developmental context, but qualify necessity because later stable knockout lines appeared normal in PMID:36332486. The protein synthesizes a steroid mediator rather than serving as a mechanical epiboly component. Supporting Evidence: PMID:23671259 Antisense morpholino knockdown studies confirmed abnormal gastrulation in cyp11a1 morphants. PMID:16437115 This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. PMID:36332486 Both homozygous cyp11a1 knockout lines appeared normal. |
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