CYP17A1 is an endoplasmic-reticulum membrane heme cytochrome P450 expressed in human adrenal cortex and gonads. Its 17alpha-hydroxylase activity converts pregnenolone and progesterone to their 17alpha-hydroxy derivatives, supplying cortisol synthesis and androgen precursors. Its distinct oxidative 17,20-lyase reaction removes the C17 side chain to produce C19 steroids. Human lyase activity strongly favors the Delta5 substrate 17alpha-hydroxypregnenolone, yielding DHEA; 17alpha-hydroxyprogesterone is a much poorer lyase substrate. POR supplies reducing equivalents from NADPH, and cytochrome b5 enhances lyase coupling and can supply the second electron. Loss-of-function variants impair corticosteroid and sex-steroid synthesis.
Definition: Catalysis of oxidative cleavage of the C17-C20 bond of a 17alpha-hydroxy-C21 steroid using molecular oxygen and reducing equivalents, producing a C19 17-ketosteroid and acetate. Substrates include 17alpha-hydroxypregnenolone and 17alpha-hydroxyprogesterone.
Justification: GO:0004508 is defined only as 17alpha hydroxylation (RHEA:65760), not side-chain cleavage. QuickGO searches for 17,20-lyase and EC1.14.14.32 found no specific term. EC1.14.14.32 and RHEA:50244/14753 in the curated human CYP17A1 record specify this distinct oxidative reaction.
Parent term: oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042446 hormone biosynthetic process | IBA GO_REF:0000033 | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001209526 SUPPORTS TRANSFER The inherited broad claim is compatible with target biology. Target-specific biochemical or localization evidence supports the more precise replacement. This review does not dispute the ancestral node placement or infer a propagation failure from donor count; the full PAINT tree was not reanalyzed. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Steroid 17-alpha-monooxygenase activity is the canonical, phylogenetically conserved molecular function of CYP17A1 and is the term most directly capturing its core catalytic role. This IBA is well corroborated by multiple experimental annotations (IDA/EXP/IMP). Reason: This is the core molecular function of the enzyme, supported by the PANTHER family and by direct experimental evidence (structures, kinetics, and mutant characterization). Supporting Evidence: PMID:9452426 P450c17 is the single enzyme that file:human/CYP17A1/CYP17A1-uniprot.txt A cytochrome P450 monooxygenase involved in corticoid and |
| GO:0042448 progesterone metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Progesterone is directly hydroxylated to 17alpha-hydroxyprogesterone. This precise substrate-level metabolic role is part of core catalysis and does not imply that progesterone is synthesized by CYP17A1. Reason: Progesterone is directly hydroxylated to 17alpha-hydroxyprogesterone. This precise substrate-level metabolic role is part of core catalysis and does not imply that progesterone is synthesized by CYP17A1. Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites |
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Reason: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Proposed replacements: steroid 17-alpha-monooxygenase activity steroid 17,20-lyase activity Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (UniProt/RHEA/EC) assignment of the correct core molecular function steroid 17-alpha-monooxygenase activity, consistent with EC 1.14.14.19/1.14.14.32. Reason: Correct core MF, redundant with the experimentally supported GO:0004508 annotations. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt A cytochrome P450 monooxygenase involved in corticoid and |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Reason: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Supporting Evidence: PMID:22266943 bind the haem iron |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CYP17A1 is a microsomal P450 localized to the endoplasmic reticulum membrane, consistent with UniProt subcellular location and multiple Reactome annotations. Reason: Correct core cellular location for this microsomal steroidogenic P450. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0008202 steroid metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0008395 steroid hydroxylase activity | IEA GO_REF:0000117 | MODIFY | Summary: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Reason: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Proposed replacements: steroid 17-alpha-monooxygenase activity steroid 17,20-lyase activity Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MODIFY | Summary: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Reason: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Proposed replacements: steroid 17-alpha-monooxygenase activity steroid 17,20-lyase activity Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen | IEA GO_REF:0000117 | MODIFY | Summary: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Reason: The broad P450 oxidation function is correct. Resolve the established steroid 17alpha-hydroxylation reaction and the distinct oxidative 17,20-lyase activity; these are not evidence-code-specific errors. Proposed replacements: steroid 17-alpha-monooxygenase activity steroid 17,20-lyase activity Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Reason: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Supporting Evidence: PMID:22266943 bind the haem iron |
| GO:0034308 primary alcohol metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Refine primary-alcohol metabolism to the directly supported cortisol biosynthetic pathway. Reason: Live QuickGO confirms GO:0034651 is_a GO:0034650 is_a GO:0034308, and also GO:0034651 is_a GO:0034309 is_a GO:0034308. Cortisol biosynthesis is therefore a true descendant refinement. CYP17A1 performs the steroid 17alpha-hydroxylation supplying the cortisol pathway; substrate-level activity is supported by the cited structural/enzymatic study. Proposed replacements: cortisol biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites |
| GO:0042445 hormone metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0120254 olefinic compound metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: This broad chemical-class metabolic term is true through cortisol biosynthesis (verified QuickGO ancestry); refine it to cortisol biosynthesis already supported in this review, rather than calling it over-annotation. Reason: This broad chemical-class metabolic term is true through cortisol biosynthesis (verified QuickGO ancestry); refine it to cortisol biosynthesis already supported in this review, rather than calling it over-annotation. Proposed replacements: cortisol biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites |
| GO:0006702 androgen biosynthetic process | TAS Reactome:R-HSA-193048 | ACCEPT | Summary: Via its 17,20-lyase activity, CYP17A1 catalyzes the committed step that generates C19 androgen precursors (DHEA, androstenedione), so androgen biosynthetic process is a correct core biological process. Reason: Core biological process; CYP17A1 is the gatekeeper of the androgen branch of steroidogenesis. Supporting Evidence: PMID:22266943 catalyses the biosynthesis of androgens in humans PMID:9452426 the 17,20-lyase activity that cleaves the C17-C20 bond to produce C19 sex steroids |
| GO:0006704 glucocorticoid biosynthetic process | TAS Reactome:R-HSA-194002 | ACCEPT | Summary: The 17-alpha-hydroxylase activity of CYP17A1 produces 17-alpha-hydroxyprogesterone, the precursor required for cortisol (glucocorticoid) synthesis, so glucocorticoid biosynthetic process is a correct core biological process. Reason: Core biological process; CYP17A1 17-alpha-hydroxylation is required for the glucocorticoid (cortisol) branch of adrenal steroidogenesis. Supporting Evidence: PMID:25301938 glucocorticoids involved in immune and stress responses |
| GO:0006704 glucocorticoid biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway-derived electronic annotation to the same glucocorticoid biosynthetic process supported by the Reactome TAS annotation; correct core biological process. Reason: Correct core BP, consistent with the UniProt PATHWAY (glucocorticoid biosynthesis) and the Reactome TAS annotation. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Steroid biosynthesis; glucocorticoid biosynthesis. |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-193068 | ACCEPT | Summary: Reactome reaction "CYP17A1 17-hydroxylates PREG" annotates the core steroid 17-alpha-monooxygenase activity. Reason: Correct core MF; Reactome curated the 17-alpha-hydroxylation of pregnenolone. Supporting Evidence: PMID:9452426 P450c17 is the single enzyme that |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-193070 | ACCEPT | Summary: Reactome reaction "CYP17A1 cleaves 17aHPREG to DHA" annotates the core steroid 17-alpha-monooxygenase/lyase activity (DHEA production). Reason: The hydroxylase activity is directly established by other human primary studies and remains accepted consistently across rows. This particular Reactome entry describes the separate 17,20-lyase reaction, so it is not itself direct evidence for hydroxylation; see reference_review. Supporting Evidence: PMID:9452426 the 17,20-lyase activity that cleaves the C17-C20 bond to produce C19 sex steroids |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-193072 | ACCEPT | Summary: Reactome reaction "CYP17A1 17-hydroxylates P4 to 17aHPROG" annotates the core steroid 17-alpha-monooxygenase activity (progesterone hydroxylation). Reason: Correct core MF; 17-alpha-hydroxylation of progesterone. Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-193099 | ACCEPT | Summary: Reactome reaction "CYP17A1 cleaves 17aHPROG to ANDST" annotates the core steroid 17-alpha-monooxygenase/lyase activity (androstenedione production). Reason: The hydroxylase activity is directly established by other human primary studies and remains accepted consistently across rows. This particular Reactome entry describes the separate 17,20-lyase reaction, so it is not itself direct evidence for hydroxylation; see reference_review. Supporting Evidence: PMID:9452426 the 17,20-lyase activity that cleaves the C17-C20 bond to produce C19 sex steroids |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-5601843 | ACCEPT | Summary: Reactome reaction (defective CYP17A1 does not 17-hydroxylate PREG) annotates the core steroid 17-alpha-monooxygenase activity in the context of loss-of-function disease. Reason: Correct core MF, curated in the AH5 disease context. Supporting Evidence: PMID:24140098 loss-of-function mutations in CYP17A1 |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-9035954 | ACCEPT | Summary: Reactome reaction (defective CYP17A1 does not 17-hydroxylate P4) annotates the core steroid 17-alpha-monooxygenase activity in the loss-of-function disease context. Reason: Correct core MF, curated in the AH5 disease context. Supporting Evidence: PMID:24140098 loss-of-function mutations in CYP17A1 |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS Reactome:R-HSA-9035956 | ACCEPT | Summary: Reactome reaction (defective CYP17A1 does not cleave 17aHPROG) annotates the core steroid 17-alpha-monooxygenase/lyase activity in the loss-of-function disease context. Reason: Correct core MF, curated in the AH5 disease context. Supporting Evidence: PMID:24140098 loss-of-function mutations in CYP17A1 |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IDA PMID:9452426 Cytochrome b5 augments the 17,20-lyase activity of human P45... | ACCEPT | Summary: Auchus et al. functionally characterized human P450c17 17-alpha-hydroxylase and 17,20-lyase activities in reconstituted yeast microsomes; direct experimental evidence for the core MF. Reason: Experimental (IDA) support for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:9452426 P450c17 is the single enzyme that |
| GO:0034651 cortisol biosynthetic process | IDA PMID:9452426 Cytochrome b5 augments the 17,20-lyase activity of human P45... | ACCEPT | Summary: CYP17A1 17-alpha-hydroxylation of 21-carbon steroids produces the 17-OH intermediates required for cortisol synthesis; this IDA annotates the specific cortisol biosynthetic process, the most precise glucocorticoid-branch BP term. Reason: Correct, specific core biological process; the 17-alpha-hydroxylase step is obligatory for cortisol biosynthesis. Supporting Evidence: PMID:9452426 17alpha-hydroxylation of 21-carbon steroids |
| GO:0004508 steroid 17-alpha-monooxygenase activity | EXP PMID:25301938 Structures of human steroidogenic cytochrome P450 17A1 with ... | ACCEPT | Summary: Petrunak et al. determined substrate-bound CYP17A1 structures and characterized its hydroxylase/lyase catalysis; experimental support for the core MF. Reason: Experimental (EXP) support for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and |
| GO:0004508 steroid 17-alpha-monooxygenase activity | EXP PMID:27339894 Mechanism of 17Ξ±,20-Lyase and New Hydroxylation Reactions of... | ACCEPT | Summary: Yoshimoto et al. mechanistically characterized the 17-alpha,20-lyase and hydroxylation reactions of human P450 17A1; experimental support for the core MF. Reason: Experimental (EXP) support for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:27339894 17Ξ±,20-lyase reactions of human P450 17A1 |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IDA PMID:36640554 Hydroxylation and lyase reactions of steroids catalyzed by m... | ACCEPT | Summary: Lee et al. purified and characterized CYP17A1 (mouse ortholog) hydroxylation and lyase reactions with progesterone and pregnenolone; direct evidence for the conserved core MF. Reason: Experimental (IDA) support for the core steroid 17-alpha-monooxygenase activity; UniProt cites this paper as experimental evidence for the human enzyme's activities. Supporting Evidence: PMID:36640554 catalyzes 17Ξ±-hydroxylation and 17,20-lyase |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IMP PMID:24140098 A review of the literature on common CYP17A1 mutations in ad... | ACCEPT | Summary: Kim et al. characterized loss-of-function CYP17A1 mutations that impair 17-alpha-hydroxylase/ 17,20-lyase activity in patients with 17-hydroxylase/17,20-lyase deficiency; mutant-phenotype (IMP) support for the core MF. Reason: Mutant-based experimental support (IMP) for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:24140098 loss-of-function mutations in CYP17A1 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5601843 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the endoplasmic reticulum membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9035954 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the endoplasmic reticulum membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9035956 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the endoplasmic reticulum membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IMP PMID:22170710 A missense mutation in the human cytochrome b5 gene causes 4... | ACCEPT | Summary: Idkowiak et al. described a CYB5A missense mutation causing true isolated 17,20-lyase deficiency, demonstrating that the CYP17A1-catalyzed lyase activity depends on cytochrome b5; supports the core CYP17A1 monooxygenase/lyase function via its partner-dependent regulation. Note the mutation studied is in CYB5A (b5), not CYP17A1, but the paper directly addresses CYP17A1 lyase function. Reason: Experimental (IMP) annotation retained; the paper establishes b5-dependence of CYP17A1 17,20-lyase activity. The full text (available) characterizes CYP17A1 lyase function; per curation policy, the curator's experimental annotation is respected. Supporting Evidence: PMID:22170710 severely reduced 17,20 lyase activity PMID:22170710 bifunctional enzyme cytochrome P450 (CYP) enzyme |
| GO:0004508 steroid 17-alpha-monooxygenase activity | IDA PMID:22266943 Structures of cytochrome P450 17A1 with prostate cancer drug... | ACCEPT | Summary: DeVore & Scott solved CYP17A1 crystal structures and characterized its dual hydroxylase/ lyase catalysis; direct experimental support for the core MF. Reason: Experimental (IDA) support for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:22266943 catalyses the biosynthesis of androgens in humans |
| GO:0008202 steroid metabolic process | IDA PMID:22266943 Structures of cytochrome P450 17A1 with prostate cancer drug... | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0020037 heme binding | IDA PMID:22266943 Structures of cytochrome P450 17A1 with prostate cancer drug... | ACCEPT | Summary: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Reason: Heme and its iron are essential catalytic cofactors of CYP17A1; structural and spectroscopic evidence support this core cofactor-binding property. Supporting Evidence: PMID:22266943 bind the haem iron |
| GO:0042446 hormone biosynthetic process | IDA PMID:22266943 Structures of cytochrome P450 17A1 with prostate cancer drug... | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0042448 progesterone metabolic process | IDA PMID:22266943 Structures of cytochrome P450 17A1 with prostate cancer drug... | ACCEPT | Summary: Progesterone is directly hydroxylated to 17alpha-hydroxyprogesterone. This precise substrate-level metabolic role is part of core catalysis and does not imply that progesterone is synthesized by CYP17A1. Reason: Progesterone is directly hydroxylated to 17alpha-hydroxyprogesterone. This precise substrate-level metabolic role is part of core catalysis and does not imply that progesterone is synthesized by CYP17A1. Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-193068 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the ER membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-193070 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the ER membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-193072 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the ER membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-193099 | ACCEPT | Summary: Reactome localizes the CYP17A1 reaction to the ER membrane, consistent with the microsomal P450 subcellular location. Reason: Correct core cellular location. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | NAS PMID:9326943 The genetic and functional basis of isolated 17,20-lyase def... | ACCEPT | Summary: CYP17A1 has supported endoplasmic reticulum localization, retained separately from its subcompartment annotations. Reason: The original PMID:9326943 abstract explicitly identifies microsomal cytochrome P450c17. Independently curated UniProt location links ER/microsome membrane to PMID:2808364. These support core ER localization; retain the organelle separately from its membrane annotation rather than call it non-core solely because it is broader. Under the root-organelle policy, retain this supported organelle assertion and its separate subcompartment claims. Supporting Evidence: file:human/CYP17A1/CYP17A1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane PMID:9326943 microsomal cytochrome P450c17 |
| GO:0019825 oxygen binding | TAS PMID:2808364 Deletion of a phenylalanine in the N-terminal region of huma... | ACCEPT | Summary: Oxygen binding is a directly measured step in human CYP17A1 catalysis, including oxyferrous-complex formation; newer kinetic evidence supports the claim even though the original variant paper is less informative. Reason: Oxygen binding is a directly measured step in human CYP17A1 catalysis, including oxyferrous-complex formation; newer kinetic evidence supports the claim even though the original variant paper is less informative. Supporting Evidence: PMID:40340376 Steps prior to and including oxygen binding were rapid for both reactions |
| GO:0004508 steroid 17-alpha-monooxygenase activity | TAS PMID:1347802 Identification by molecular cloning of an autoantigen associ... | ACCEPT | Summary: Krohn et al. identified the Addison's-disease autoantigen by molecular cloning as steroid 17-alpha-hydroxylase (CYP17A1); supports the core MF assignment. Reason: Author-stated (TAS) support for the core steroid 17-alpha-monooxygenase activity. Supporting Evidence: PMID:1347802 steroid 17 alpha-hydroxylase |
| GO:0006694 steroid biosynthetic process | TAS PMID:3500022 Cloning and sequence of the human gene for P450c17 (steroid ... | MODIFY | Summary: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Reason: CYP17A1 directly supplies cortisol and androgen biosynthesis. These specific core processes refine the broad steroid/hormone metabolism or biosynthesis label, rather than making the function peripheral. Proposed replacements: cortisol biosynthetic process androgen biosynthetic process Supporting Evidence: PMID:25301938 both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17Ξ±-hydroxy major metabolites PMID:40340376 In contrast, the 17,20-lyase reaction involves cleavage of a carbon-carbon bond rather than the equivalent of oxygen insertion into a carbon-hydrogen bond |
| GO:0007548 sex differentiation | TAS PMID:9326943 The genetic and functional basis of isolated 17,20-lyase def... | KEEP AS NON CORE | Summary: Steroid production contributes to sexual differentiation; the cited human loss-of-function study supports this developmental outcome, which is downstream of the core catalytic role. Reason: Steroid production contributes to sexual differentiation; the cited human loss-of-function study supports this developmental outcome, which is downstream of the core catalytic role. Supporting Evidence: PMID:9326943 Human male sexual differentiation requires production of fetal testicular testosterone |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)