Steroid 17-alpha-hydroxylase/17,20 lyase
Details
- Name
- Steroid 17-alpha-hydroxylase/17,20 lyase
- Kind
- protein
- Synonyms
- 1.14.14.19
- 17-alpha-hydroxyprogesterone aldolase
- CYP17
- CYPXVII
- Cytochrome P450 17A1
- Cytochrome P450-C17
- Cytochrome P450c17
- S17AH
- Steroid 17-alpha-monooxygenase
- Gene Name
- CYP17A1
- UniProtKB Entry
- P05093Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0018942|Steroid 17-alpha-hydroxylase/17,20 lyase MWELVALLLLTLAYLFWPKRRCPGAKYPKSLLSLPLVGSLPFLPRHGHMHNNFFKLQKKY GPIYSVRMGTKTTVIVGHHQLAKEVLIKKGKDFSGRPQMATLDIASNNRKGIAFADSGAH WQLHRRLAMATFALFKDGDQKLEKIICQEISTLCDMLATHNGQSIDISFPVFVAVTNVIS LICFNTSYKNGDPELNVIQNYNEGIIDNLSKDSLVDLVPWLKIFPNKTLEKLKSHVKIRN DLLNKILENYKEKFRSDSITNMLDTLMQAKMNSDNGNAGPDQDSELLSDNHILTTIGDIF GAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQNVGFSRTPTISDRNRLLLLEATIREV LRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWALHHNEKEWHQPDQFMPERFLNP AGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLLQRFDLEVPDDGQLPSLEGIP KVVFLIDSFKVKIKVRQAWREAQAEGST
- Number of residues
- 508
- Molecular Weight
- 57369.995
- Theoretical pI
- 8.87
- GO Classification
- Functionslyase activity
- General 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)
- Specific Function
- heme binding
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0018943|Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) ATGTGGGAGCTCGTGGCTCTCTTGCTGCTTACCCTAGCTTATTTGTTTTGGCCCAAGAGA AGGTGCCCTGGTGCCAAGTACCCCAAGAGCCTCCTGTCCCTGCCCCTGGTGGGCAGCCTG CCATTCCTCCCCAGACACGGCCATATGCATAACAACTTCTTCAAGCTGCAGAAAAAATAT GGCCCCATCTATTCGGTTCGTATGGGCACCAAGACTACAGTGATTGTCGGCCACCACCAG CTGGCCAAGGAGGTGCTTATTAAGAAGGGCAAGGACTTCTCTGGGCGGCCTCAAATGGCA ACTCTAGACATCGCGTCCAACAACCGTAAGGGTATCGCCTTCGCTGACTCTGGCGCACAC TGGCAGCTGCATCGAAGGCTGGCGATGGCCACCTTTGCCCTGTTCAAGGATGGCGATCAG AAGCTGGAGAAGATCATTTGTCAGGAAATCAGTACATTGTGTGATATGCTGGCCACCCAC AACGGACAGTCCATAGACATCTCCTTTCCTGTCTTCGTGGCGGTAACCAATGTCATCTCC TTGATCTGCTTCAATACCTCCTACAAGAATGGGGACCCTGAGTTGAATGTCATACAGAAT TACAATGAAGGCATCATAGACAACCTGAGCAAAGACAGCCTGGTGGACCTAGTCCCCTGG TTGAAGATTTTCCCCAACAAAACCCTGGAAAAATTAAAGAGCCATGTTAAAATACGAAAT GATCTGCTGAATAAAATACTTGAAAATTACAAGGAGAAATTCCGGAGTGACTCTATCACC AACATGCTGGACACACTGATGCAAGCCAAGATGAACTCAGATAATGGCAATGCTGGCCCA GATCAAGACTCAGAGCTGCTTTCAGATAACCACATTCTCACCACCATAGGGGACATCTTT GGGGCTGGCGTGGAGACCACCACCTCTGTGGTTAAATGGACCCTGGCCTTCCTGCTGCAC AATCCTCAGGTGAAGAAGAAGCTCTACGAGGAGATTGACCAGAATGTGGGTTTCAGCCGC ACACCAACTATCAGTGACCGTAACCGTCTCCTCCTGCTGGAGGCCACCATCCGAGAGGTG CTTCGCCTCAGGCCCGTGGCCCCTATGCTCATCCCCCACAAGGCCAACGTTGACTCCAGC ATCGGTGAGTTTGCTGTGGACAAGGGCACAGAAGTTATCATCAATCTGTGGGCGCTGCAT CACAATGAGAAGGAGTGGCACCAGCCGGATCAGTTCATGCCTGAGCGTTTCTTGAATCCA GCGGGGACCCAGCTCATCTCACCGTCAGTAAGCTATTTGCCCTTCGGAGCAGGACCTCGC TCCTGTATAGGTGAGATCCTGGCCCGCCAGGAGCTCTTCCTCATCATGGCCTGGCTGCTG CAGAGGTTCGACCTGGAGGTGCCAGATGATGGGCAGCTGCCCTCCCTGGAAGGCATCCCC AAGGTGGTCTTTCTGATCGACTCTTTCAAAGTGAAGATCAAGGTGCGCCAGGCCTGGAGG GAAGCCCAGGCTGAGGGTAGCACCTAA
- Chromosome Location
- 10
- Locus
- 10q24.32
- External Identifiers
Resource Link UniProtKB ID P05093 UniProtKB Entry Name CP17A_HUMAN GenBank Protein ID 181342 GenBank Gene ID M14564 GeneCard ID CYP17A1 GenAtlas ID CYP17A1 HGNC ID HGNC:2593 PDB ID(s) 3RUK, 3SWZ, 4NKV, 4NKW, 4NKX, 4NKY, 4NKZ, 5IRQ, 5IRV, 5UYS, 6CHI, 6CIR, 6CIZ, 6WR0, 6WR1, 6WW0, 8FDA KEGG ID hsa:1586 IUPHAR/Guide To Pharmacology ID 1361 NCBI Gene ID 1586 - General References
- Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, Miller WL: Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(2):407-11. [Article]
- Picado-Leonard J, Miller WL: Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. DNA. 1987 Oct;6(5):439-48. [Article]
- Bradshaw KD, Waterman MR, Couch RT, Simpson ER, Zuber MX: Characterization of complementary deoxyribonucleic acid for human adrenocortical 17 alpha-hydroxylase: a probe for analysis of 17 alpha-hydroxylase deficiency. Mol Endocrinol. 1987 May;1(5):348-54. [Article]
- Brentano ST, Picado-Leonard J, Mellon SH, Moore CC, Miller WL: Tissue-specific, cyclic adenosine 3',5'-monophosphate-induced, and phorbol ester-repressed transcription from the human P450c17 promoter in mouse cells. Mol Endocrinol. 1990 Dec;4(12):1972-9. [Article]
- Kagimoto M, Winter JS, Kagimoto K, Simpson ER, Waterman MR: Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency. Mol Endocrinol. 1988 Jun;2(6):564-70. [Article]
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- Lin D, Harikrishna JA, Moore CC, Jones KL, Miller WL: Missense mutation serine106----proline causes 17 alpha-hydroxylase deficiency. J Biol Chem. 1991 Aug 25;266(24):15992-8. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details NADH approved, nutraceutical unknown target Details Progesterone approved, vet_approved unknown target substrateinhibitor Details Abiraterone approved yes target inhibitor Details Aldosterone experimental, investigational unknown enzyme inducer Details Aminophenazone approved, withdrawn unknown enzyme substrate Details Stanolone illicit, investigational unknown enzyme substrate Details Dexamethasone approved, investigational, vet_approved unknown enzyme inhibitor Details Progesterone approved, vet_approved unknown enzyme inhibitor Details Ketoconazole approved, investigational yes target inhibitor Details Clomifene approved, investigational unknown enzyme inhibitor Details Cannabidiol approved, investigational unknown target inhibitor Details Nabiximols investigational unknown target inhibitor Details Medical Cannabis experimental, investigational unknown target inhibitor Details Prasterone approved, investigational, nutraceutical unknown enzyme product of Details Dexamethasone acetate approved, investigational, vet_approved unknown enzyme inhibitor Details Levoketoconazole approved, investigational yes target inhibitor Details Isoconazole approved yes target inhibitor Details CFG-920 investigational yes target inhibitor Details Seviteronel investigational yes target inhibitor Details