P05093 · CP17A_HUMAN
- ProteinSteroid 17-alpha-hydroxylase/17,20 lyase
- GeneCYP17A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids508 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426).
Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426).
Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426).
Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554).
Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894).
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426).
Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426).
Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426).
Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554).
Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894).
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426).
Catalytic activity
- a C21-steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 17alpha-hydroxy-C21-steroid + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha,17alpha-dihydroxyprogesterone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 16alpha,17alpha-dihydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 6beta,16alpha,17alpha-trihydroxyprogesterone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 16alpha,17alpha-dihydroxypregnenolone + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + acetate + 2 H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyandrost-4-ene-3,17-dione + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Regulated predominantly by intracellular cAMP levels (PubMed:10720067).
The 17,20-lyase activity is stimulated by cytochrome b5, which acts as an allosteric effector increasing the Vmax of the lyase activity (PubMed:27339894, PubMed:9452426).
The 17,20-lyase activity is stimulated by cytochrome b5, which acts as an allosteric effector increasing the Vmax of the lyase activity (PubMed:27339894, PubMed:9452426).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
10.5 μM | progesterone (17-alpha hydroxylation) | |||||
5.87 μM | progesterone (17-alpha hydroxylation) | |||||
0.93 μM | pregnenolone (17-alpha hydroxylation) | |||||
1.19 μM | pregnenolone (17-alpha hydroxylation) | |||||
1.2 μM | 17alpha-hydroxypregnenolone (17,20 lyase activity) | |||||
21.9 μM | 17alpha-hydroxyprogesterone (17,20 lyase activity) |
kcat is 1.01 min-1 with progesterone as substrate. kcat is 0.39 min-1 with pregnenolone as substrate. kcat is 0.24 min-1 with 17alpha-hydroxypregnenolone as substrate.
Pathway
Steroid hormone biosynthesis.
Steroid biosynthesis; glucocorticoid biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axon | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | neuronal cell body | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | lyase activity | |
Molecular Function | oxygen binding | |
Molecular Function | steroid 17-alpha-monooxygenase activity | |
Biological Process | androgen biosynthetic process | |
Biological Process | glucocorticoid biosynthetic process | |
Biological Process | hormone biosynthetic process | |
Biological Process | progesterone metabolic process | |
Biological Process | sex differentiation | |
Biological Process | steroid biosynthetic process | |
Biological Process | steroid metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameSteroid 17-alpha-hydroxylase/17,20 lyase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP05093
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Adrenal hyperplasia 5 (AH5)
- Note
- DescriptionA form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic).
- See alsoMIM:202110
Natural variants in AH5
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_022745 | 35 | P>L | in AH5; 38% 17alpha-hydroxylase activity and 33% 17,20-lyase activity | |
VAR_001270 | 53 | missing | in AH5; 10% 17alpha-hydroxylase activity and 13% 17,20-lyase activity | |
VAR_001271 | 64 | Y>S | in AH5; dbSNP:rs1183147390 | |
VAR_013147 | 93 | F>C | in AH5; dbSNP:rs104894146 | |
VAR_073043 | 96 | R>Q | in AH5; dbSNP:rs104894153 | |
VAR_022746 | 96 | R>W | in AH5; 25% of both 17alpha-hydroxylase and 17,20-lyase activities; dbSNP:rs104894138 | |
VAR_001272 | 106 | S>P | in AH5; dbSNP:rs104894135 | |
VAR_001273 | 112 | I>II | in AH5 | |
VAR_022747 | 114 | F>V | in AH5; dbSNP:rs104894147 | |
VAR_022748 | 116 | D>V | in AH5; dbSNP:rs104894148 | |
VAR_073044 | 121 | W>R | in AH5; partial loss of activity | |
VAR_073045 | 174 | A>E | in AH5; dbSNP:rs752540777 | |
VAR_022749 | 177 | N>D | in AH5; 10% 17alpha-hydroxylase and 17,20-lyase activities | |
VAR_022750 | 329 | Y>D | in AH5; dbSNP:rs104894144 | |
VAR_022751 | 330 | missing | in AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities; dbSNP:rs759060233 | |
VAR_001274 | 342 | P>T | in AH5; dbSNP:rs104894137 | |
VAR_022752 | 347 | R>C | in AH5; dbSNP:rs104894149 | |
VAR_001275 | 347 | R>H | in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity; dbSNP:rs61754278 | |
VAR_001276 | 358 | R>Q | in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity; dbSNP:rs104894139 | |
VAR_022753 | 362 | R>C | in AH5; dbSNP:rs104894142 | |
VAR_001277 | 373 | H>L | in AH5; dbSNP:rs760695410 | |
VAR_073046 | 373 | H>N | in AH5; dbSNP:rs1423560123 | |
VAR_073047 | 406 | W>L | in AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities | |
VAR_022754 | 406 | W>R | in AH5; dbSNP:rs104894143 | |
VAR_022755 | 417 | F>C | in AH5; ablates both 17,20-lyase activity and 17alpha-hydroxylase activity; loss of heme-binding and loss of phosphorylation; dbSNP:rs104894140 | |
VAR_022756 | 428 | P>L | in AH5; dbSNP:rs104894145 | |
VAR_001278 | 440 | R>H | in AH5; dbSNP:rs777638364 | |
VAR_001279 | 487-489 | missing | in AH5 | |
VAR_001280 | 496 | R>C | in AH5; dbSNP:rs1250463562 | |
VAR_022757 | 496 | R>H | in AH5; 30% 17alpha-hydroxylase activity and 29% 17,20-lyase activity; dbSNP:rs763398879 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_011755 | 22 | in dbSNP:rs762563 | |||
Sequence: C → W | ||||||
Natural variant | VAR_022745 | 35 | in AH5; 38% 17alpha-hydroxylase activity and 33% 17,20-lyase activity | |||
Sequence: P → L | ||||||
Natural variant | VAR_001270 | 53 | in AH5; 10% 17alpha-hydroxylase activity and 13% 17,20-lyase activity | |||
Sequence: Missing | ||||||
Natural variant | VAR_001271 | 64 | in AH5; dbSNP:rs1183147390 | |||
Sequence: Y → S | ||||||
Natural variant | VAR_013147 | 93 | in AH5; dbSNP:rs104894146 | |||
Sequence: F → C | ||||||
Natural variant | VAR_073043 | 96 | in AH5; dbSNP:rs104894153 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_022746 | 96 | in AH5; 25% of both 17alpha-hydroxylase and 17,20-lyase activities; dbSNP:rs104894138 | |||
Sequence: R → W | ||||||
Mutagenesis | 105 | Increases the affinity for progesterone, resulting in preferential hydroxylation of progesterone at C17 over C16; increases the catalytic efficiency in the 17,20 lyase reaction. | ||||
Sequence: A → L | ||||||
Natural variant | VAR_001272 | 106 | in AH5; dbSNP:rs104894135 | |||
Sequence: S → P | ||||||
Natural variant | VAR_001273 | 112 | in AH5 | |||
Sequence: I → II | ||||||
Natural variant | VAR_022747 | 114 | in AH5; dbSNP:rs104894147 | |||
Sequence: F → V | ||||||
Natural variant | VAR_022748 | 116 | in AH5; dbSNP:rs104894148 | |||
Sequence: D → V | ||||||
Natural variant | VAR_073044 | 121 | in AH5; partial loss of activity | |||
Sequence: W → R | ||||||
Natural variant | VAR_073045 | 174 | in AH5; dbSNP:rs752540777 | |||
Sequence: A → E | ||||||
Natural variant | VAR_022749 | 177 | in AH5; 10% 17alpha-hydroxylase and 17,20-lyase activities | |||
Sequence: N → D | ||||||
Natural variant | VAR_022750 | 329 | in AH5; dbSNP:rs104894144 | |||
Sequence: Y → D | ||||||
Natural variant | VAR_022751 | 330 | in AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities; dbSNP:rs759060233 | |||
Sequence: Missing | ||||||
Natural variant | VAR_001274 | 342 | in AH5; dbSNP:rs104894137 | |||
Sequence: P → T | ||||||
Natural variant | VAR_022752 | 347 | in AH5; dbSNP:rs104894149 | |||
Sequence: R → C | ||||||
Natural variant | VAR_001275 | 347 | in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity; dbSNP:rs61754278 | |||
Sequence: R → H | ||||||
Natural variant | VAR_001276 | 358 | in AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity; dbSNP:rs104894139 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_022753 | 362 | in AH5; dbSNP:rs104894142 | |||
Sequence: R → C | ||||||
Natural variant | VAR_001277 | 373 | in AH5; dbSNP:rs760695410 | |||
Sequence: H → L | ||||||
Natural variant | VAR_073046 | 373 | in AH5; dbSNP:rs1423560123 | |||
Sequence: H → N | ||||||
Natural variant | VAR_073047 | 406 | in AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities | |||
Sequence: W → L | ||||||
Natural variant | VAR_022754 | 406 | in AH5; dbSNP:rs104894143 | |||
Sequence: W → R | ||||||
Natural variant | VAR_022755 | 417 | in AH5; ablates both 17,20-lyase activity and 17alpha-hydroxylase activity; loss of heme-binding and loss of phosphorylation; dbSNP:rs104894140 | |||
Sequence: F → C | ||||||
Natural variant | VAR_022756 | 428 | in AH5; dbSNP:rs104894145 | |||
Sequence: P → L | ||||||
Natural variant | VAR_001278 | 440 | in AH5; dbSNP:rs777638364 | |||
Sequence: R → H | ||||||
Natural variant | VAR_001279 | 487-489 | in AH5 | |||
Sequence: Missing | ||||||
Natural variant | VAR_001280 | 496 | in AH5; dbSNP:rs1250463562 | |||
Sequence: R → C | ||||||
Natural variant | VAR_022757 | 496 | in AH5; 30% 17alpha-hydroxylase activity and 29% 17,20-lyase activity; dbSNP:rs763398879 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 549 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000051931 | 1-508 | UniProt | Steroid 17-alpha-hydroxylase/17,20 lyase | |||
Sequence: MWELVALLLLTLAYLFWPKRRCPGAKYPKSLLSLPLVGSLPFLPRHGHMHNNFFKLQKKYGPIYSVRMGTKTTVIVGHHQLAKEVLIKKGKDFSGRPQMATLDIASNNRKGIAFADSGAHWQLHRRLAMATFALFKDGDQKLEKIICQEISTLCDMLATHNGQSIDISFPVFVAVTNVISLICFNTSYKNGDPELNVIQNYNEGIIDNLSKDSLVDLVPWLKIFPNKTLEKLKSHVKIRNDLLNKILENYKEKFRSDSITNMLDTLMQAKMNSDNGNAGPDQDSELLSDNHILTTIGDIFGAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQNVGFSRTPTISDRNRLLLLEATIREVLRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWALHHNEKEWHQPDQFMPERFLNPAGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLLQRFDLEVPDDGQLPSLEGIPKVVFLIDSFKVKIKVRQAWREAQAEGST | |||||||
Modified residue (large scale data) | 258 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation is necessary for 17,20-lyase, but not for 17-alpha-hydroxylase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Sequence
- Sequence statusComplete
- Length508
- Mass (Da)57,371
- Last updated1987-08-13 v1
- ChecksumE5454E9E18F96B0E
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1W2PQ28 | A0A1W2PQ28_HUMAN | CYP17A1 | 356 | ||
A0A1W2PQT5 | A0A1W2PQT5_HUMAN | CYP17A1 | 479 | ||
A0A1W2PRK7 | A0A1W2PRK7_HUMAN | CYP17A1 | 509 | ||
A0A1W2PRY0 | A0A1W2PRY0_HUMAN | CYP17A1 | 407 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M14564 EMBL· GenBank· DDBJ | AAA52151.1 EMBL· GenBank· DDBJ | mRNA | ||
M19489 EMBL· GenBank· DDBJ | AAA36405.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M63871 EMBL· GenBank· DDBJ | AAA59984.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M31153 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31146 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31147 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31148 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31149 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31150 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31151 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
M31152 EMBL· GenBank· DDBJ | AAA52140.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
BT020000 EMBL· GenBank· DDBJ | AAV38803.1 EMBL· GenBank· DDBJ | mRNA | ||
AL358790 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC062997 EMBL· GenBank· DDBJ | AAH62997.1 EMBL· GenBank· DDBJ | mRNA | ||
BC063388 EMBL· GenBank· DDBJ | AAH63388.1 EMBL· GenBank· DDBJ | mRNA |