CYP17A1

UniProt ID: P05093
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

CYP17A1 (cytochrome P450c17; steroid 17-alpha-hydroxylase/17,20 lyase) is a microsomal, endoplasmic-reticulum-membrane heme-thiolate cytochrome P450 monooxygenase that sits at the central branch point of steroidogenesis. It is a single bifunctional enzyme with two catalytic activities on one polypeptide: (1) 17-alpha-hydroxylase (EC 1.14.14.19), which hydroxylates the C21 steroids pregnenolone and progesterone to their 17-alpha-hydroxy derivatives (precursors of the glucocorticoid cortisol), and (2) 17,20-lyase (EC 1.14.14.32), which cleaves the C17-C20 bond of the 17-alpha-hydroxy intermediates to generate the C19 androgen precursors dehydroepiandrosterone (from 17-alpha-hydroxypregnenolone) and androstenedione (from 17-alpha-hydroxyprogesterone), the committed step toward androgens and estrogens. The relative use of the hydroxylase-only versus hydroxylase-plus-lyase route determines whether steroid flux is directed to cortisol or to sex steroids. Catalysis is a cytochrome-P450 monooxygenase reaction using molecular oxygen, with two electrons supplied by NADPH via cytochrome P450 reductase (POR); the 17,20-lyase activity additionally requires cytochrome b5, which acts as an allosteric effector that increases the lyase Vmax without direct electron transfer. The enzyme is predominantly expressed in the adrenal cortex and gonads. Loss-of-function of CYP17A1 causes combined 17-alpha-hydroxylase/17,20-lyase deficiency (a form of congenital adrenal hyperplasia, MIM:202110), presenting with hypertension and defective sexual development; isolated 17,20-lyase deficiency (46,XY disorder of sex development) also occurs. CYP17A1 is a validated drug target: the inhibitor abiraterone blocks androgen synthesis in castration-resistant prostate cancer.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0042446 hormone biosynthetic process
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: CYP17A1 catalyzes committed steps in the biosynthesis of steroid hormones (glucocorticoids and sex steroids), so hormone biosynthetic process is correct. It is a broad grouping term; the specific glucocorticoid/cortisol and androgen biosynthetic process annotations are more informative for the core function.
Reason: Accurate phylogenetic annotation but too general to represent the core function on its own; the specific downstream biosynthesis terms (androgen, glucocorticoid, cortisol) are the core BP annotations.
Supporting Evidence:
PMID:25301938
controlling the levels of mineralocorticoids influencing
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
KEEP AS NON CORE
Summary: CYP17A1 metabolizes progesterone (17-alpha-hydroxylation of progesterone to 17-alpha-hydroxyprogesterone, and further lyase cleavage), so progesterone metabolic process is a correct, if general, annotation.
Reason: Substrate-level metabolic term is accurate but not the primary biological role; the steroid-hormone biosynthetic processes are the core BP annotations.
Supporting Evidence:
PMID:36640554
progesterone and pregnenolone
GO:0004497 monooxygenase activity
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Monooxygenase activity is a correct but very general parent of the specific steroid 17-alpha-monooxygenase activity (GO:0004508) that CYP17A1 enables.
Reason: This InterPro-derived term is an ancestor of the specific MF GO:0004508 that is already annotated with experimental evidence; it is redundant/over-general for the core function.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
A cytochrome P450 monooxygenase involved in corticoid and
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
KEEP AS NON CORE
Summary: CYP17A1 is a heme-thiolate P450 whose heme iron (axial Cys442) is essential for catalysis; iron ion binding is correct as a supporting molecular function.
Reason: Accurate cofactor/metal-binding annotation but supportive (part of the heme active site) rather than the enzyme's defining catalytic function.
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
KEEP AS NON CORE
Summary: Steroid metabolic process is correct but a broad grouping term; the specific steroid hormone biosynthetic processes are more informative.
Reason: Accurate but over-general parent of the specific androgen/glucocorticoid biosynthetic processes that constitute the core function.
Supporting Evidence:
PMID:22266943
catalyses the biosynthesis of androgens in humans
GO:0008395 steroid hydroxylase activity
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: Steroid hydroxylase activity correctly describes the 17-alpha-hydroxylase reaction but is a parent of the more specific GO:0004508 steroid 17-alpha-monooxygenase activity.
Reason: Over-general parent of the specific, experimentally supported core MF GO:0004508.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
A cytochrome P450 monooxygenase involved in corticoid and
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Correct high-level oxidoreductase/monooxygenase parent term for a cytochrome P450, but much more general than the specific GO:0004508.
Reason: InterPro-derived ancestor of the specific core MF; retained by the ontology for the P450 fold but over-general for the gene's function.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
two electrons provided
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
MARK AS OVER ANNOTATED
Summary: Describes the P450/POR (flavoprotein donor) monooxygenase mechanism; correct mechanistically but a general parent of the specific steroid 17-alpha-monooxygenase activity.
Reason: Mechanistic ancestor term (reduced flavoprotein donor, one oxygen atom incorporated); over-general relative to the specific core MF GO:0004508.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
two electrons provided
GO:0020037 heme binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: CYP17A1 is a heme-thiolate cytochrome P450; heme binding is a correct, essential supporting molecular function (heme is the catalytic prosthetic group).
Reason: Accurate cofactor-binding function that supports, but does not define, the enzyme's catalytic activity; retained as a secondary (non-core) molecular function.
Supporting Evidence:
PMID:22266943
bind the haem iron
GO:0034308 primary alcohol metabolic process
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: This ARBA electronic term derives from the enzyme's hydroxylation chemistry (introducing hydroxyl groups). It does not correspond to a recognized biological role of CYP17A1; steroid 17-alpha-hydroxyl products are not usefully described as "primary alcohol metabolism".
Reason: Chemistry-derived over-annotation; not a biologically meaningful process term for this steroidogenic enzyme. The relevant BP is steroid hormone biosynthesis.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
A cytochrome P450 monooxygenase involved in corticoid and
GO:0042445 hormone metabolic process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Correct but broad grouping term; CYP17A1 participates in steroid hormone metabolism. The specific biosynthesis terms are more informative.
Reason: Accurate general parent of the specific hormone biosynthetic processes.
Supporting Evidence:
PMID:25301938
controlling the levels of mineralocorticoids influencing
GO:0120254 olefinic compound metabolic process
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: This ARBA electronic term derives from the fact that steroid substrates contain carbon-carbon double bonds; it is a chemistry-based over-general grouping that does not describe a biologically meaningful role of CYP17A1.
Reason: Chemistry-derived over-annotation with no biological specificity for this enzyme; the meaningful process is steroid hormone biosynthesis.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
A cytochrome P450 monooxygenase involved in corticoid and
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: Correct core MF; captures the 17,20-lyase cleavage step producing DHEA.
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: Correct core MF; captures the 17,20-lyase cleavage step producing androstenedione.
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...
KEEP AS NON CORE
Summary: Steroid metabolic process is a correct but broad grouping; the specific androgen/ glucocorticoid biosynthetic processes are more informative for the core function.
Reason: Accurate but over-general parent of the specific steroid hormone biosynthetic processes.
Supporting Evidence:
PMID:22266943
catalyses the biosynthesis of androgens in humans
GO:0020037 heme binding
IDA
PMID:22266943
Structures of cytochrome P450 17A1 with prostate cancer drug...
KEEP AS NON CORE
Summary: Crystal structures show CYP17A1 binds heme (inhibitors coordinate the heme iron), directly demonstrating heme binding; essential supporting cofactor function.
Reason: Experimentally supported cofactor-binding function; supportive of, but not the defining catalytic role of, the enzyme. Retained as secondary molecular function.
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...
KEEP AS NON CORE
Summary: CYP17A1 biosynthesizes steroid hormones (androgens, glucocorticoid precursors); correct but general BP term.
Reason: Accurate general parent of the specific androgen/glucocorticoid biosynthetic processes.
Supporting Evidence:
PMID:22266943
catalyses the biosynthesis of androgens in humans
GO:0042448 progesterone metabolic process
IDA
PMID:22266943
Structures of cytochrome P450 17A1 with prostate cancer drug...
KEEP AS NON CORE
Summary: CYP17A1 hydroxylates progesterone (17-alpha-hydroxylation) and further cleaves the product; progesterone metabolic process is correct at substrate level.
Reason: Accurate substrate-level metabolic term; the steroid hormone biosynthetic processes are the core BP annotations.
Supporting Evidence:
PMID:25301938
both hydroxylase substrates pregnenolone and
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...
KEEP AS NON CORE
Summary: Endoplasmic reticulum is a correct (if less specific) location for this microsomal P450; the ER membrane term (GO:0005789) is more precise.
Reason: Correct but less-specific parent of the ER membrane location; retained as non-core in favor of the more precise GO:0005789.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
Microsome membrane
GO:0019825 oxygen binding
TAS
PMID:2808364
Deletion of a phenylalanine in the N-terminal region of huma...
MARK AS OVER ANNOTATED
Summary: Oxygen binding is a legacy (ProtInc/PINC) annotation. Although CYP17A1 uses molecular oxygen as a co-substrate in its monooxygenase mechanism, "oxygen binding" (typically used for reversible O2 carriers such as hemoglobin/myoglobin) is not an informative molecular function for a P450 monooxygenase, and the cited reference (PubMed:2808364, on the F53 deletion causing combined deficiency) does not address oxygen binding.
Reason: Legacy, uninformative MF for a P450; the O2 co-substrate chemistry is already captured by the monooxygenase/oxidoreductase terms. Not a genuine reversible-oxygen-binding activity.
Supporting Evidence:
file:human/CYP17A1/CYP17A1-uniprot.txt
two electrons provided
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 ...
KEEP AS NON CORE
Summary: Picado-Leonard & Miller describe P450c17 as a single cytochrome P450 mediating both 17-alpha-hydroxylase and 17,20-lyase activities in steroid hormone biosynthesis; steroid biosynthetic process is correct but a broad parent of the specific biosynthesis terms.
Reason: Accurate but over-general parent of the specific androgen/glucocorticoid biosynthetic processes.
Supporting Evidence:
PMID:3500022
single cytochrome P450 enzyme mediating both 17 alpha-hydroxylase
GO:0007548 sex differentiation
TAS
PMID:9326943
The genetic and functional basis of isolated 17,20-lyase def...
KEEP AS NON CORE
Summary: CYP17A1 17,20-lyase activity is required for fetal testicular androgen (testosterone precursor) production, and its deficiency causes disorders of sexual development; sex differentiation is an accurate but downstream/systemic process rather than the enzyme's direct molecular role.
Reason: Accurate downstream physiological consequence of androgen biosynthesis; not the enzyme's direct core molecular/biological function, so retained as non-core.
Supporting Evidence:
PMID:9326943
male sexual differentiation requires production of fetal testicular

Core Functions

Steroid 17-alpha-hydroxylase activity (EC 1.14.14.19): as a microsomal cytochrome P450 monooxygenase, CYP17A1 hydroxylates the C21 steroids pregnenolone and progesterone at C17 to yield 17-alpha-hydroxypregnenolone and 17-alpha-hydroxyprogesterone, the obligatory precursors for cortisol (glucocorticoid) biosynthesis, using O2 and electrons from NADPH via cytochrome P450 reductase.

Supporting Evidence:
  • PMID:9452426
    17alpha-hydroxylation of 21-carbon steroids
  • PMID:25301938
    both hydroxylase substrates pregnenolone and
  • file:human/CYP17A1/CYP17A1-uniprot.txt
    A cytochrome P450 monooxygenase involved in corticoid and

Steroid 17,20-lyase activity (EC 1.14.14.32): CYP17A1 cleaves the C17-C20 bond of the 17-alpha-hydroxy intermediates (17-alpha-hydroxypregnenolone -> dehydroepiandrosterone; 17-alpha-hydroxyprogesterone -> androstenedione), the committed step generating C19 androgen precursors. This second oxidative activity resides on the same polypeptide as the hydroxylase and requires cytochrome b5 as an allosteric effector (with POR as the electron donor), determining the flux of steroidogenesis toward androgens and estrogens.

Supporting Evidence:
  • PMID:9452426
    the 17,20-lyase activity that cleaves the C17-C20 bond to produce C19 sex steroids
  • PMID:9452426
    coexpression of human b5 with P450c17 also
  • PMID:22266943
    catalyses the biosynthesis of androgens in humans

Heme binding: CYP17A1 is a heme-thiolate cytochrome P450 whose heme prosthetic group (iron axially coordinated by Cys442) is essential for its monooxygenase/lyase catalysis; heme/iron binding is the supporting cofactor function underpinning both catalytic activities.

Molecular Function:
heme binding
Supporting Evidence:

References

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Notes

(CYP17A1-notes.md)

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