Tclin CYP17A1 Steroid 17-alpha-hydroxylase/17,20 lyase

Protein Summary

Description

Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P05093
• Q5TZV7

Gene Name

• CYP17A1

Ensembl ID

• ENST00000369887
• ENSP00000358903
• ENSG00000148795

Symbol

• CYP17
• S17AH
• CPT7
• CYP17
• S17AH
• P450C17

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	0.93
biological process	0.9
disease	0.79
molecular function	0.76
cellular component	0.72

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1561.78   (req: < 5)

Gene RIFs: 311   (req: <= 3)

Antibodies: 545   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1561.78   (req: >= 5)

Gene RIFs: 311   (req: > 3)

Antibodies: 545   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 477

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 7

Approved Drugs (7)

Explore Approved Drugs

1 – 7 of 7

clotrimazole

CYP17A1Tclin Enzyme

Ki : 7.09

econazole

CYP17A1Tclin Enzyme

Ki : 6.49

miconazole

CYP17A1Tclin Enzyme

Ki : 6.61

ketoconazole

CYP17A1Tclin Enzyme

INHIBITOR IC50 : 7.28

bifonazole

CYP17A1Tclin Enzyme

Ki : 7.25

testosterone propionate

CYP17A1Tclin Enzyme

IC50 : 7.25

abiraterone acetate

CYP17A1Tclin Enzyme

INHIBITOR IC50 : 8.54

Active Ligands (477)

Explore Active Ligands

1 – 10 of 477

CHEMBL295698

CYP17A1Tclin Enzyme

Ki : 7.42

CHEMBL1172882

CYP17A1Tclin Enzyme

IC50 : 7.01

CHEMBL1173260

CYP17A1Tclin Enzyme

IC50 : 6.73

CHEMBL305220

CYP17A1Tclin Enzyme

Ki : 7.27

CHEMBL307160

CYP17A1Tclin Enzyme

IC50 : 6.89

CHEMBL78322

CYP17A1Tclin Enzyme

IC50 : 7.38

CHEMBL362968,CHEMBL460178

CYP17A1Tclin Enzyme

IC50 : 6.18

CHEMBL2333326

CYP17A1Tclin Enzyme

IC50 : 6.58

CHEMBL2333336

CYP17A1Tclin Enzyme

IC50 : 6.31

CHEMBL1083652

CYP17A1Tclin Enzyme

IC50 : 6.06

GWAS Traits (8)

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5

1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	1	1	1		76.1
colorectal cancer	EFO_0005842	1	1	0	1.1	68.7
hypertension	EFO_0000537	2	1	2		68.2
worry measurement	EFO_0009589	1	1	1		60.6
neuroticism measurement	EFO_0007660	1	1	1		49.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	1		76.1
colorectal cancer	EFO_0005842	0	1.1	68.7
hypertension	EFO_0000537	2		68.2
worry measurement	EFO_0009589	1		60.6
neuroticism measurement	EFO_0007660	1		49.1

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450, family 17, subfamily A, polypeptide 1		450141
Macaque	cytochrome P450c17		678693
Mouse	cytochrome P450, family 17, subfamily a, polypeptide 1	MGI:88586	13074
Rat	cytochrome P450, family 17, subfamily a, polypeptide 1	RGD:2456	25146
Dog	cytochrome P450 family 17 subfamily A member 1	VGNC:50330	477807

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450, family 17, subfamily A, polypeptide 1
Macaque	cytochrome P450c17
Mouse	cytochrome P450, family 17, subfamily a, polypeptide 1
Rat	cytochrome P450, family 17, subfamily a, polypeptide 1
Dog	cytochrome P450 family 17 subfamily A member 1

Protein Structure (14 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P05093-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 14

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (24)

Reactome (10)

KEGG (6)

PathwayCommons (1)

UniProt (1)

WikiPathways (6)

Androgen biosynthesis (R-HSA-193048)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Androgen biosynthesis	11 targets	R-HSA-193048
Reactome	Defective CYP17A1 causes Adrenal hyperplasia 5 (AH5)	1 targets	R-HSA-5579028
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of metabolism	103 targets	R-HSA-5668914
Reactome	Glucocorticoid biosynthesis	9 targets	R-HSA-194002

Name	Explore in Pharos	Explore in Source
Androgen biosynthesis	11 targets	R-HSA-193048
Defective CYP17A1 causes Adrenal hyperplasia 5 (AH5)	1 targets	R-HSA-5579028
Disease	1105 targets	R-HSA-1643685
Diseases of metabolism	103 targets	R-HSA-5668914
Glucocorticoid biosynthesis	9 targets	R-HSA-194002

Gene Ontology Terms (17)

Functions (5)

Components (4)

Processes (8)

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10

1 – 5 of 5

GO Term	Evidence	Assigned by
heme binding	Inferred from Direct Assay (IDA)	UniProtKB
steroid 17-alpha-monooxygenase activity	Inferred from Direct Assay (IDA)	UniProtKB
17-alpha-hydroxyprogesterone aldolase activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
oxygen binding	Traceable Author Statement (TAS)	ProtInc
iron ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (127)

Explore Interacting Targets

1 – 10 of 127

• See Interactions on String-DB

HSD3B1

Tchem

Family: Enzyme

Novelty: 0.0019271

Score: 0.993

Data Source: STRINGDB

HSD3B2

Tclin

Family: Enzyme

Novelty: 0.00711552

Score: 0.989

Data Source: STRINGDB

HSD17B6

Tbio

Family: Enzyme

Novelty: 0.01428594

Score: 0.986

Data Source: STRINGDB

HSD17B3

Tchem

Family: Enzyme

Novelty: 0.00666322

Score: 0.98

Data Source: STRINGDB

SRD5A2

Tclin

Family: Enzyme

Novelty: 0.00281044

Score: 0.973

Data Source: STRINGDB

SRD5A1

Tclin

Family: Enzyme

Novelty: 0.00987219

Score: 0.972

Data Source: STRINGDB

AKR1C3

Tchem

Family: Enzyme

Novelty: 0.00257785

Score: 0.966

Data Source: STRINGDB

HSD17B2

Tchem

Family: Enzyme

Novelty: 0.00960865

Score: 0.96

Data Source: STRINGDB

CYP11A1

Tclin

Family: Enzyme

Novelty: 0.00096368

Score: 0.953

Data Source: STRINGDB

CYP11B1

Tclin

Family: Enzyme

Novelty: 0.00195229

Score: 0.95

Data Source: STRINGDB

Publication Statistics

PubMed Score  1561.78

PubMed score by year

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PubTator Score  1029.54

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Complete proteome
Congenital adrenal hyperplasia
Disease mutation
Heme
Iron
Lyase
Membrane
Metal-binding
Monooxygenase

GWAS Trait Find Similar Targets

colorectal cancer
depressive symptom measurement
hip circumference
hypertension
neuroticism measurement
testosterone measurement
waist circumference
worry measurement

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
homeostasis/metabolism phenotype
mortality/aging
reproductive system phenotype
skeleton phenotype