CP17A_HUMAN
ID CP17A_HUMAN Reviewed; 508 AA.
AC P05093; Q5TZV7;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Steroid 17-alpha-hydroxylase/17,20 lyase {ECO:0000303|PubMed:3025870};
DE EC=1.14.14.19 {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894};
DE AltName: Full=17-alpha-hydroxyprogesterone aldolase;
DE EC=1.14.14.32 {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894};
DE AltName: Full=CYPXVII;
DE AltName: Full=Cytochrome P450 17A1 {ECO:0000303|PubMed:27339894};
DE AltName: Full=Cytochrome P450-C17;
DE Short=Cytochrome P450c17 {ECO:0000303|PubMed:8396144};
DE AltName: Full=Steroid 17-alpha-monooxygenase;
GN Name=CYP17A1 {ECO:0000303|PubMed:19793597, ECO:0000312|HGNC:HGNC:2593};
GN Synonyms=CYP17, S17AH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3025870; DOI=10.1073/pnas.84.2.407;
RA Chung B.-C., Picado-Leonard J., Haniu M., Bienkowski M., Hall P.F.,
RA Shively J.E., Miller W.L.;
RT "Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of
RT human adrenal and testis cDNAs indicates the same gene is expressed in both
RT tissues.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:407-411(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3500022; DOI=10.1089/dna.1987.6.439;
RA Picado-Leonard J., Miller W.L.;
RT "Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-
RT hydroxylase/17,20 lyase): similarity with the gene for P450c21.";
RL DNA 6:439-448(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3274893; DOI=10.1210/mend-1-5-348;
RA Bradshaw K.D., Waterman M.R., Couch R.T., Simpson E.R., Zuber M.X.;
RT "Characterization of complementary deoxyribonucleic acid for human
RT adrenocortical 17 alpha-hydroxylase: a probe for analysis of 17 alpha-
RT hydroxylase deficiency.";
RL Mol. Endocrinol. 1:348-354(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1964490; DOI=10.1210/mend-4-12-1972;
RA Brentano S.T., Picado-Leonard J., Mellon S.H., Moore C.C., Miller W.L.;
RT "Tissue-specific, cyclic adenosine 3',5'-monophosphate-induced, and phorbol
RT ester-repressed transcription from the human P450c17 promoter in mouse
RT cells.";
RL Mol. Endocrinol. 4:1972-1979(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2843762; DOI=10.1210/mend-2-6-564;
RA Kagimoto M., Winter J.S.D., Kagimoto K., Simpson E.R., Waterman M.R.;
RT "Structural characterization of normal and mutant human steroid 17 alpha-
RT hydroxylase genes: molecular basis of one example of combined 17 alpha-
RT hydroxylase/17,20 lyase deficiency.";
RL Mol. Endocrinol. 2:564-570(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=9452426; DOI=10.1074/jbc.273.6.3158;
RA Auchus R.J., Lee T.C., Miller W.L.;
RT "Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without
RT direct electron transfer.";
RL J. Biol. Chem. 273:3158-3165(1998).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=27339894; DOI=10.1074/jbc.m116.732966;
RA Yoshimoto F.K., Gonzalez E., Auchus R.J., Guengerich F.P.;
RT "Mechanism of 17alpha,20-Lyase and New Hydroxylation Reactions of Human
RT Cytochrome P450 17A1: 18O LABELING AND OXYGEN SURROGATE EVIDENCE FOR A ROLE
RT OF A PERFERRYL OXYGEN.";
RL J. Biol. Chem. 291:17143-17164(2016).
RN [11]
RP 3D-STRUCTURE MODELING OF 48-501.
RX PubMed=10406467; DOI=10.1210/mend.13.7.0326;
RA Auchus R.J., Miller W.L.;
RT "Molecular modeling of human P450c17 (17alpha-hydroxylase/17,20-lyase):
RT insights into reaction mechanisms and effects of mutations.";
RL Mol. Endocrinol. 13:1169-1182(1999).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 24-508 IN COMPLEXES WITH HEME;
RP ABIRATERONE AND TOK-001, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP PATHWAY.
RX PubMed=22266943; DOI=10.1038/nature10743;
RA DeVore N.M., Scott E.E.;
RT "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone
RT and TOK-001.";
RL Nature 482:116-119(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 24-508 IN COMPLEX WITH HEME AND
RP PREGNENOLONE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND MUTAGENESIS OF ALA-105.
RX PubMed=25301938; DOI=10.1074/jbc.m114.610998;
RA Petrunak E.M., DeVore N.M., Porubsky P.R., Scott E.E.;
RT "Structures of human steroidogenic cytochrome P450 17A1 with substrates.";
RL J. Biol. Chem. 289:32952-32964(2014).
RN [14]
RP VARIANT AH5 PHE-53 DEL, AND SUBCELLULAR LOCATION.
RX PubMed=2808364; DOI=10.1016/s0021-9258(19)84680-x;
RA Yanase T., Kagimoto M., Suzuki S., Hashiba K., Simpson E.R., Waterman M.R.;
RT "Deletion of a phenylalanine in the N-terminal region of human cytochrome
RT P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-
RT lyase deficiency.";
RL J. Biol. Chem. 264:18076-18082(1989).
RN [15]
RP VARIANT AH5 PRO-106.
RX PubMed=1714904; DOI=10.1016/s0021-9258(18)98506-6;
RA Lin D., Harikrishna J.A., Moore C.C.D., Jones K.L., Miller W.L.;
RT "Missense mutation serine106-->proline causes 17 alpha-hydroxylase
RT deficiency.";
RL J. Biol. Chem. 266:15992-15998(1991).
RN [16]
RP VARIANT AH5 CYS-496.
RX PubMed=1515452; DOI=10.1016/0925-4439(92)90100-2;
RA Yanase T., Waterman M.R., Zachmann M., Winter J.S.D., Kagimoto M.;
RT "Molecular basis of apparent isolated 17,20-lyase deficiency: compound
RT heterozygous mutations in the C-terminal region (Arg(496)-->Cys,
RT Gln(461)-->Stop) actually cause combined 17 alpha-hydroxylase/17,20-lyase
RT deficiency.";
RL Biochim. Biophys. Acta 1139:275-279(1992).
RN [17]
RP VARIANT AH5 THR-342.
RX PubMed=1740503; DOI=10.1210/jcem.74.3.1740503;
RA Ahlgren R., Yanase T., Simpson E.R., Winter J.S.D., Waterman M.R.;
RT "Compound heterozygous mutations (Arg 239-->Stop, Pro 342-->Thr) in the
RT CYP17 (P45017 alpha) gene lead to ambiguous external genitalia in a male
RT patient with partial combined 17 alpha-hydroxylase/17,20-lyase
RT deficiency.";
RL J. Clin. Endocrinol. Metab. 74:667-672(1992).
RN [18]
RP VARIANTS AH5 SER-64 AND ILE-112 INS.
RX PubMed=8396144; DOI=10.1016/s0021-9258(19)36570-6;
RA Imai T., Globerman H., Gertner J.M., Kagawa N., Waterman M.R.;
RT "Expression and purification of functional human 17 alpha-
RT hydroxylase/17,20-lyase (P450c17) in Escherichia coli. Use of this system
RT for study of a novel form of combined 17 alpha-hydroxylase/17,20-lyase
RT deficiency.";
RL J. Biol. Chem. 268:19681-19689(1993).
RN [19]
RP VARIANT AH5 LEU-373.
RX PubMed=8245018; DOI=10.1016/s0021-9258(19)74462-7;
RA Monno S., Ogawa H., Date T., Fujioka M., Miller W.L., Kobayashi M.;
RT "Mutation of histidine 373 to leucine in cytochrome P450c17 causes 17
RT alpha-hydroxylase deficiency.";
RL J. Biol. Chem. 268:25811-25817(1993).
RN [20]
RP VARIANT AH5 487-ASP--PHE-489 DEL.
RX PubMed=8345056; DOI=10.1210/jcem.77.2.8345056;
RA Fardella C.E., Zhang L.H., Mahacholklertwattana P., Lin D., Miller W.L.;
RT "Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17
RT causes severe 17 alpha-hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 77:489-493(1993).
RN [21]
RP VARIANT AH5 HIS-440.
RX PubMed=8027220; DOI=10.1210/jcem.79.1.8027220;
RA Fardella C.E., Hum D.W., Homoki J., Miller W.L.;
RT "Point mutation of Arg440 to His in cytochrome P450c17 causes severe 17
RT alpha-hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 79:160-164(1994).
RN [22]
RP VARIANT AH5 TRP-96.
RX PubMed=8550762; DOI=10.1210/jcem.81.1.8550762;
RA Laflamme N., Leblanc J.-F., Mailloux J., Faure N., Labrie F., Simard J.;
RT "Mutation R96W in cytochrome P450c17 gene causes combined 17 alpha-
RT hydroxylase/17-20-lyase deficiency in two French Canadian patients.";
RL J. Clin. Endocrinol. Metab. 81:264-268(1996).
RN [23]
RP VARIANTS AH5 HIS-347 AND GLN-358.
RA Geller D.H., Mendonca B.B., Miller W.L.;
RT "The molecular basis of isolated 17,20 lyase deficiency.";
RL Pediatr. Res. 39:89A-89A(1996).
RN [24]
RP VARIANTS AH5 LEU-35; PHE-53 DEL; TRP-96; ASP-177; GLU-330 DEL; CYS-417 AND
RP HIS-496, AND PHOSPHORYLATION.
RX PubMed=10720067; DOI=10.1210/jcem.85.3.6475;
RA Biason-Lauber A., Kempken B., Werder E., Forest M.G., Einaudi S.,
RA Ranke M.B., Matsuo N., Brunelli V., Schoenle E.J., Zachmann M.;
RT "17alpha-hydroxylase/17,20-lyase deficiency as a model to study enzymatic
RT activity regulation: role of phosphorylation.";
RL J. Clin. Endocrinol. Metab. 85:1226-1231(2000).
RN [25]
RP VARIANTS AH5 HIS-347; GLN-358 AND CYS-417.
RX PubMed=11549685; DOI=10.1210/jcem.86.9.7812;
RA Gupta M.K., Geller D.H., Auchus R.J.;
RT "Pitfalls in characterizing P450c17 mutations associated with isolated
RT 17,20-lyase deficiency.";
RL J. Clin. Endocrinol. Metab. 86:4416-4423(2001).
RN [26]
RP VARIANT AH5 CYS-93.
RX PubMed=11836339; DOI=10.1210/jcem.87.2.8271;
RA Di Cerbo A., Biason-Lauber A., Savino M., Piemontese M.R., Di Giorgio A.,
RA Perona M., Savoia A.;
RT "Combined 17alpha-hydroxylase/17,20-lyase deficiency caused by Phe93Cys
RT mutation in the CYP17 gene.";
RL J. Clin. Endocrinol. Metab. 87:898-905(2002).
RN [27]
RP VARIANTS AH5 VAL-114; VAL-116; CYS-347 AND HIS-347.
RX PubMed=12466376; DOI=10.1210/jc.2001-011880;
RA Van Den Akker E.L.T., Koper J.W., Boehmer A.L.M., Themmen A.P.N.,
RA Verhoef-Post M., Timmerman M.A., Otten B.J., Drop S.L.S., De Jong F.H.;
RT "Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities
RT by three novel missense CYP17 mutations identified in patients with P450c17
RT deficiency.";
RL J. Clin. Endocrinol. Metab. 87:5714-5721(2002).
RN [28]
RP VARIANTS AH5 TRP-96; ASP-329; CYS-362; ARG-406 AND LEU-428.
RX PubMed=14671162; DOI=10.1210/jc.2003-030988;
RA Martin R.M., Lin C.J., Costa E.M.F., de Oliveira M.L., Carrilho A.,
RA Villar H., Longui C.A., Mendonca B.B.;
RT "P450c17 deficiency in Brazilian patients: biochemical diagnosis through
RT progesterone levels confirmed by CYP17 genotyping.";
RL J. Clin. Endocrinol. Metab. 88:5739-5746(2003).
RN [29]
RP VARIANTS AH5 PHE-53 DEL AND ASN-373.
RX PubMed=19793597; DOI=10.1016/j.metabol.2009.07.024;
RA Katsumata N., Ogawa E., Fujiwara I., Fujikura K.;
RT "Novel CYP17A1 mutation in a Japanese patient with combined 17alpha-
RT hydroxylase/17,20-lyase deficiency.";
RL Metabolism 59:275-278(2010).
RN [30]
RP VARIANT AH5 GLN-96.
RX PubMed=24498484; DOI=10.5001/omj.2014.12;
RA Mula-Abed W.A., Pambinezhuth F.B., Al-Kindi M.K., Al-Busaidi N.B.,
RA Al-Muslahi H.N., Al-Lamki M.A.;
RT "Congenital adrenal hyperplasia due to 17-alpha-hydoxylase/17,20-lyase
RT deficiency presenting with hypertension and pseudohermaphroditism: first
RT case report from Oman.";
RL Oman Med. J. 29:55-59(2014).
RN [31]
RP VARIANTS AH5 GLU-174; LEU-373 AND LEU-406, AND CHARACTERIZATION OF VARIANT
RP AH5 LEU-406.
RX PubMed=24140098; DOI=10.1016/j.metabol.2013.08.015;
RA Kim Y.M., Kang M., Choi J.H., Lee B.H., Kim G.H., Ohn J.H., Kim S.Y.,
RA Park M.S., Yoo H.W.;
RT "A review of the literature on common CYP17A1 mutations in adults with 17-
RT hydroxylase/17,20-lyase deficiency, a case series of such mutations among
RT Koreans and functional characteristics of a novel mutation.";
RL Metabolism 63:42-49(2014).
RN [32]
RP VARIANT AH5 ARG-121, AND CHARACTERIZATION OF VARIANT AH5 ARG-121.
RX PubMed=25650406; DOI=10.1530/eje-14-0834;
RA Rubtsov P., Nizhnik A., Dedov I.I., Kalinchenko N., Petrov V., Orekhova A.,
RA Spirin P., Prassolov V., Tiulpakov A.;
RT "Partial deficiency of 17alpha-hydroxylase/17,20-lyase caused by a novel
RT missense mutation in the canonical cytochrome heme-interacting motif.";
RL Eur. J. Endocrinol. 172:K19-25(2015).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in corticoid and
CC androgen biosynthesis (PubMed:9452426, PubMed:27339894,
CC PubMed:22266943, PubMed:25301938). Catalyzes 17-alpha hydroxylation of
CC C21 steroids, which is common for both pathways. A second oxidative
CC step, required only for androgen synthesis, involves an acyl-carbon
CC cleavage. The 17-alpha hydroxy intermediates, as part of adrenal
CC glucocorticoids biosynthesis pathway, are precursors of cortisol
CC (PubMed:9452426, PubMed:25301938) (Probable). Hydroxylates steroid
CC hormones, pregnenolone and progesterone to form 17-alpha hydroxy
CC metabolites, followed by the cleavage of the C17-C20 bond to form C19
CC steroids, dehydroepiandrosterone (DHEA) and androstenedione
CC (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938).
CC Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of
CC 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20
CC bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates
CC androgens, relevant for estriol synthesis (PubMed:27339894,
CC PubMed:25301938). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9452426,
CC PubMed:27339894, PubMed:22266943, PubMed:25301938).
CC {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938,
CC ECO:0000269|PubMed:27339894, ECO:0000269|PubMed:9452426,
CC ECO:0000305|PubMed:8027220}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a C21-steroid + O2 + reduced [NADPH--hemoprotein reductase] =
CC a 17alpha-hydroxy-C21-steroid + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:65760, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:61313, ChEBI:CHEBI:138141; EC=1.14.14.19;
CC Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938,
CC ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65761;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC 17alpha-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:46308, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17026, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19;
CC Evidence={ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:9452426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46309;
CC Evidence={ECO:0000305|PubMed:9452426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + pregnenolone + reduced [NADPH--hemoprotein reductase] =
CC 17alpha-hydroxypregnenolone + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:50236, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:28750,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19;
CC Evidence={ECO:0000269|PubMed:9452426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50237;
CC Evidence={ECO:0000305|PubMed:9452426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein
CC reductase] = acetate + androst-4-ene-3,17-dione + 2 H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:14753,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17252, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.32;
CC Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14754;
CC Evidence={ECO:0000305|PubMed:22266943};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein
CC reductase] = 16alpha,17alpha-dihydroxyprogesterone + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53216,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:763,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53217;
CC Evidence={ECO:0000305|PubMed:27339894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16alpha,17alpha-dihydroxyprogesterone + O2 + reduced [NADPH--
CC hemoprotein reductase] = 6beta,16alpha,17alpha-trihydroxyprogesterone
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:763, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:137046; Evidence={ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53221;
CC Evidence={ECO:0000305|PubMed:27339894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-hydroxypregnenolone + O2 + reduced [NADPH--hemoprotein
CC reductase] = 3beta-hydroxyandrost-5-en-17-one + acetate + 2 H(+) +
CC H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50244,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28689,
CC ChEBI:CHEBI:28750, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.32;
CC Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938,
CC ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50245;
CC Evidence={ECO:0000305|PubMed:22266943};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16alpha,17alpha-dihydroxypregnenolone + O2 + reduced [NADPH--
CC hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one
CC + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53224, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:27771, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:137049;
CC Evidence={ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53225;
CC Evidence={ECO:0000305|PubMed:27339894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:47220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:27771, ChEBI:CHEBI:28689, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47221;
CC Evidence={ECO:0000305|PubMed:27339894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein
CC reductase] = 16alpha-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53228,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:27582, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:27339894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53229;
CC Evidence={ECO:0000305|PubMed:27339894};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938};
CC -!- ACTIVITY REGULATION: Regulated predominantly by intracellular cAMP
CC levels (PubMed:10720067). The 17,20-lyase activity is stimulated by
CC cytochrome b5, which acts as an allosteric effector increasing the Vmax
CC of the lyase activity (PubMed:9452426, PubMed:27339894).
CC {ECO:0000269|PubMed:10720067, ECO:0000269|PubMed:27339894,
CC ECO:0000269|PubMed:9452426}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.5 uM for progesterone (17-alpha hydroxylation)
CC {ECO:0000269|PubMed:25301938};
CC KM=0.93 uM for pregnenolone (17-alpha hydroxylation)
CC {ECO:0000269|PubMed:25301938};
CC KM=1.2 uM for 17alpha-hydroxypregnenolone (17,20 lyase activity)
CC {ECO:0000269|PubMed:25301938};
CC Note=kcat is 1.01 min(-1) with progesterone as substrate. kcat is
CC 0.39 min(-1) with pregnenolone as substrate. kcat is 0.24 min(-1)
CC with 17alpha-hydroxypregnenolone as substrate.;
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:22266943,
CC ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894,
CC ECO:0000269|PubMed:9452426}.
CC -!- PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis.
CC {ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:9452426}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:2808364}. Microsome membrane
CC {ECO:0000305|PubMed:2808364}.
CC -!- PTM: Phosphorylation is necessary for 17,20-lyase, but not for 17-
CC alpha-hydroxylase activity. {ECO:0000269|PubMed:10720067}.
CC -!- DISEASE: Adrenal hyperplasia 5 (AH5) [MIM:202110]: A form of congenital
CC adrenal hyperplasia, a common recessive disease due to defective
CC synthesis of cortisol. Congenital adrenal hyperplasia is characterized
CC by androgen excess leading to ambiguous genitalia in affected females,
CC rapid somatic growth during childhood in both sexes with premature
CC closure of the epiphyses and short adult stature. Four clinical types:
CC 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV,
CC less severely affected patients), with normal aldosterone biosynthesis,
CC 'non-classic form' or late-onset (NC or LOAH) and 'cryptic'
CC (asymptomatic). {ECO:0000269|PubMed:10720067,
CC ECO:0000269|PubMed:11549685, ECO:0000269|PubMed:11836339,
CC ECO:0000269|PubMed:12466376, ECO:0000269|PubMed:14671162,
CC ECO:0000269|PubMed:1515452, ECO:0000269|PubMed:1714904,
CC ECO:0000269|PubMed:1740503, ECO:0000269|PubMed:19793597,
CC ECO:0000269|PubMed:24140098, ECO:0000269|PubMed:24498484,
CC ECO:0000269|PubMed:25650406, ECO:0000269|PubMed:2808364,
CC ECO:0000269|PubMed:8027220, ECO:0000269|PubMed:8245018,
CC ECO:0000269|PubMed:8345056, ECO:0000269|PubMed:8396144,
CC ECO:0000269|PubMed:8550762, ECO:0000269|Ref.23}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M14564; AAA52151.1; -; mRNA.
DR EMBL; M19489; AAA36405.1; -; Genomic_DNA.
DR EMBL; M63871; AAA59984.1; -; Genomic_DNA.
DR EMBL; M31153; AAA52140.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M31146; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31147; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31148; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31149; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31150; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31151; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; M31152; AAA52140.1; JOINED; Genomic_DNA.
DR EMBL; BT020000; AAV38803.1; -; mRNA.
DR EMBL; AL358790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062997; AAH62997.1; -; mRNA.
DR EMBL; BC063388; AAH63388.1; -; mRNA.
DR CCDS; CCDS7541.1; -.
DR PIR; A40921; A26366.
DR RefSeq; NP_000093.1; NM_000102.3.
DR PDB; 3RUK; X-ray; 2.60 A; A/B/C/D=24-508.
DR PDB; 3SWZ; X-ray; 2.40 A; A/B/C/D=24-508.
DR PDB; 4NKV; X-ray; 2.65 A; A/B/C/D=24-508.
DR PDB; 4NKW; X-ray; 2.50 A; A/B/C/D=24-508.
DR PDB; 4NKX; X-ray; 2.79 A; A/B/C/D=24-508.
DR PDB; 4NKY; X-ray; 2.55 A; A/B/C/D=24-508.
DR PDB; 4NKZ; X-ray; 3.00 A; A/B/C/D=24-508.
DR PDB; 5IRQ; X-ray; 2.20 A; A/B/C/D=24-508.
DR PDB; 5IRV; X-ray; 3.10 A; A/B/C/D=24-508.
DR PDB; 5UYS; X-ray; 2.39 A; A/B/C/D=24-508.
DR PDB; 6CHI; X-ray; 2.70 A; A/B/C/D=24-508.
DR PDB; 6CIR; X-ray; 2.65 A; A/B/C/D=24-508.
DR PDB; 6CIZ; X-ray; 2.60 A; A/B/C/D=24-508.
DR PDB; 6WR0; X-ray; 2.70 A; A/B/C/D=24-508.
DR PDB; 6WR1; X-ray; 1.85 A; A/B=24-508.
DR PDB; 6WW0; X-ray; 2.01 A; A/B/C/D=24-508.
DR PDBsum; 3RUK; -.
DR PDBsum; 3SWZ; -.
DR PDBsum; 4NKV; -.
DR PDBsum; 4NKW; -.
DR PDBsum; 4NKX; -.
DR PDBsum; 4NKY; -.
DR PDBsum; 4NKZ; -.
DR PDBsum; 5IRQ; -.
DR PDBsum; 5IRV; -.
DR PDBsum; 5UYS; -.
DR PDBsum; 6CHI; -.
DR PDBsum; 6CIR; -.
DR PDBsum; 6CIZ; -.
DR PDBsum; 6WR0; -.
DR PDBsum; 6WR1; -.
DR PDBsum; 6WW0; -.
DR AlphaFoldDB; P05093; -.
DR SMR; P05093; -.
DR BioGRID; 107958; 17.
DR IntAct; P05093; 13.
DR MINT; P05093; -.
DR STRING; 9606.ENSP00000358903; -.
DR BindingDB; P05093; -.
DR ChEMBL; CHEMBL3522; -.
DR DrugBank; DB05812; Abiraterone.
DR DrugBank; DB04630; Aldosterone.
DR DrugBank; DB01424; Aminophenazone.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00882; Clomifene.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB05667; Levoketoconazole.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB02901; Stanolone.
DR DrugCentral; P05093; -.
DR GuidetoPHARMACOLOGY; 1361; -.
DR SwissLipids; SLP:000001611; -.
DR iPTMnet; P05093; -.
DR PhosphoSitePlus; P05093; -.
DR BioMuta; CYP17A1; -.
DR DMDM; 117283; -.
DR MassIVE; P05093; -.
DR PaxDb; P05093; -.
DR PeptideAtlas; P05093; -.
DR PRIDE; P05093; -.
DR ProteomicsDB; 51789; -.
DR Antibodypedia; 31491; 646 antibodies from 40 providers.
DR DNASU; 1586; -.
DR Ensembl; ENST00000369887.4; ENSP00000358903.3; ENSG00000148795.7.
DR GeneID; 1586; -.
DR KEGG; hsa:1586; -.
DR MANE-Select; ENST00000369887.4; ENSP00000358903.3; NM_000102.4; NP_000093.1.
DR CTD; 1586; -.
DR DisGeNET; 1586; -.
DR GeneCards; CYP17A1; -.
DR HGNC; HGNC:2593; CYP17A1.
DR HPA; ENSG00000148795; Tissue enriched (adrenal).
DR MalaCards; CYP17A1; -.
DR MIM; 202110; phenotype.
DR MIM; 609300; gene.
DR neXtProt; NX_P05093; -.
DR OpenTargets; ENSG00000148795; -.
DR Orphanet; 90796; 46,XY disorder of sex development due to isolated 17,20-lyase deficiency.
DR Orphanet; 90793; Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency.
DR PharmGKB; PA27090; -.
DR VEuPathDB; HostDB:ENSG00000148795; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000155588; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; P05093; -.
DR OMA; GPQEAME; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P05093; -.
DR TreeFam; TF105095; -.
DR BioCyc; MetaCyc:HS07560-MON; -.
DR BRENDA; 1.14.14.19; 2681.
DR BRENDA; 1.14.14.32; 2681.
DR PathwayCommons; P05093; -.
DR Reactome; R-HSA-193048; Androgen biosynthesis.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR Reactome; R-HSA-5579028; Defective CYP17A1 causes AH5.
DR SABIO-RK; P05093; -.
DR SignaLink; P05093; -.
DR SIGNOR; P05093; -.
DR UniPathway; UPA00788; -.
DR BioGRID-ORCS; 1586; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; CYP17A1; human.
DR GeneWiki; CYP17A1; -.
DR GenomeRNAi; 1586; -.
DR Pharos; P05093; Tclin.
DR PRO; PR:P05093; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P05093; protein.
DR Bgee; ENSG00000148795; Expressed in right adrenal gland and 96 other tissues.
DR ExpressionAtlas; P05093; baseline and differential.
DR Genevisible; P05093; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; NAS:ProtInc.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0047442; F:17-alpha-hydroxyprogesterone aldolase activity; IMP:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0004508; F:steroid 17-alpha-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0006702; P:androgen biosynthetic process; TAS:Reactome.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; TAS:Reactome.
DR GO; GO:0042446; P:hormone biosynthetic process; IDA:UniProtKB.
DR GO; GO:0042448; P:progesterone metabolic process; IDA:UniProtKB.
DR GO; GO:0007548; P:sex differentiation; TAS:ProtInc.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Congenital adrenal hyperplasia; Disease variant;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Lyase; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroidogenesis.
FT CHAIN 1..508
FT /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT /id="PRO_0000051931"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25301938"
FT BINDING 442
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT VARIANT 22
FT /note="C -> W (in dbSNP:rs762563)"
FT /id="VAR_011755"
FT VARIANT 35
FT /note="P -> L (in AH5; 38% 17alpha-hydroxylase activity and
FT 33% 17,20-lyase activity)"
FT /evidence="ECO:0000269|PubMed:10720067"
FT /id="VAR_022745"
FT VARIANT 53
FT /note="Missing (in AH5; 10% 17alpha-hydroxylase activity
FT and 13% 17,20-lyase activity)"
FT /evidence="ECO:0000269|PubMed:10720067,
FT ECO:0000269|PubMed:19793597, ECO:0000269|PubMed:2808364"
FT /id="VAR_001270"
FT VARIANT 64
FT /note="Y -> S (in AH5; dbSNP:rs1183147390)"
FT /evidence="ECO:0000269|PubMed:8396144"
FT /id="VAR_001271"
FT VARIANT 93
FT /note="F -> C (in AH5; dbSNP:rs104894146)"
FT /evidence="ECO:0000269|PubMed:11836339"
FT /id="VAR_013147"
FT VARIANT 96
FT /note="R -> Q (in AH5; dbSNP:rs104894153)"
FT /evidence="ECO:0000269|PubMed:24498484"
FT /id="VAR_073043"
FT VARIANT 96
FT /note="R -> W (in AH5; 25% of both 17alpha-hydroxylase and
FT 17,20-lyase activities; dbSNP:rs104894138)"
FT /evidence="ECO:0000269|PubMed:10720067,
FT ECO:0000269|PubMed:14671162, ECO:0000269|PubMed:8550762"
FT /id="VAR_022746"
FT VARIANT 106
FT /note="S -> P (in AH5; dbSNP:rs104894135)"
FT /evidence="ECO:0000269|PubMed:1714904"
FT /id="VAR_001272"
FT VARIANT 112
FT /note="I -> II (in AH5)"
FT /evidence="ECO:0000269|PubMed:8396144"
FT /id="VAR_001273"
FT VARIANT 114
FT /note="F -> V (in AH5; dbSNP:rs104894147)"
FT /evidence="ECO:0000269|PubMed:12466376"
FT /id="VAR_022747"
FT VARIANT 116
FT /note="D -> V (in AH5; dbSNP:rs104894148)"
FT /evidence="ECO:0000269|PubMed:12466376"
FT /id="VAR_022748"
FT VARIANT 121
FT /note="W -> R (in AH5; partial loss of activity)"
FT /evidence="ECO:0000269|PubMed:25650406"
FT /id="VAR_073044"
FT VARIANT 174
FT /note="A -> E (in AH5)"
FT /evidence="ECO:0000269|PubMed:24140098"
FT /id="VAR_073045"
FT VARIANT 177
FT /note="N -> D (in AH5; 10% 17alpha-hydroxylase and 17,20-
FT lyase activities)"
FT /evidence="ECO:0000269|PubMed:10720067"
FT /id="VAR_022749"
FT VARIANT 329
FT /note="Y -> D (in AH5; dbSNP:rs104894144)"
FT /evidence="ECO:0000269|PubMed:14671162"
FT /id="VAR_022750"
FT VARIANT 330
FT /note="Missing (in AH5; complete loss of both 17alpha-
FT hydroxylase and 17,20-lyase activities; dbSNP:rs759060233)"
FT /evidence="ECO:0000269|PubMed:10720067"
FT /id="VAR_022751"
FT VARIANT 342
FT /note="P -> T (in AH5; dbSNP:rs104894137)"
FT /evidence="ECO:0000269|PubMed:1740503"
FT /id="VAR_001274"
FT VARIANT 347
FT /note="R -> C (in AH5; dbSNP:rs104894149)"
FT /evidence="ECO:0000269|PubMed:12466376"
FT /id="VAR_022752"
FT VARIANT 347
FT /note="R -> H (in AH5; selectively ablates 17,20-lyase
FT activity, while preserving most 17alpha-hydroxylase
FT activity; dbSNP:rs61754278)"
FT /evidence="ECO:0000269|PubMed:11549685,
FT ECO:0000269|PubMed:12466376, ECO:0000269|Ref.23"
FT /id="VAR_001275"
FT VARIANT 358
FT /note="R -> Q (in AH5; selectively ablates 17,20-lyase
FT activity, while preserving most 17alpha-hydroxylase
FT activity; dbSNP:rs104894139)"
FT /evidence="ECO:0000269|PubMed:11549685, ECO:0000269|Ref.23"
FT /id="VAR_001276"
FT VARIANT 362
FT /note="R -> C (in AH5; dbSNP:rs104894142)"
FT /evidence="ECO:0000269|PubMed:14671162"
FT /id="VAR_022753"
FT VARIANT 373
FT /note="H -> L (in AH5; dbSNP:rs760695410)"
FT /evidence="ECO:0000269|PubMed:24140098,
FT ECO:0000269|PubMed:8245018"
FT /id="VAR_001277"
FT VARIANT 373
FT /note="H -> N (in AH5; dbSNP:rs1423560123)"
FT /evidence="ECO:0000269|PubMed:19793597"
FT /id="VAR_073046"
FT VARIANT 406
FT /note="W -> L (in AH5; complete loss of both 17alpha-
FT hydroxylase and 17,20-lyase activities)"
FT /evidence="ECO:0000269|PubMed:24140098"
FT /id="VAR_073047"
FT VARIANT 406
FT /note="W -> R (in AH5; dbSNP:rs104894143)"
FT /evidence="ECO:0000269|PubMed:14671162"
FT /id="VAR_022754"
FT VARIANT 417
FT /note="F -> C (in AH5; ablates both 17,20-lyase activity
FT and 17alpha-hydroxylase activity; loss of heme-binding and
FT loss of phosphorylation; dbSNP:rs104894140)"
FT /evidence="ECO:0000269|PubMed:10720067,
FT ECO:0000269|PubMed:11549685"
FT /id="VAR_022755"
FT VARIANT 428
FT /note="P -> L (in AH5; dbSNP:rs104894145)"
FT /evidence="ECO:0000269|PubMed:14671162"
FT /id="VAR_022756"
FT VARIANT 440
FT /note="R -> H (in AH5; dbSNP:rs777638364)"
FT /evidence="ECO:0000269|PubMed:8027220"
FT /id="VAR_001278"
FT VARIANT 487..489
FT /note="Missing (in AH5)"
FT /evidence="ECO:0000269|PubMed:8345056"
FT /id="VAR_001279"
FT VARIANT 496
FT /note="R -> C (in AH5; dbSNP:rs1250463562)"
FT /evidence="ECO:0000269|PubMed:1515452"
FT /id="VAR_001280"
FT VARIANT 496
FT /note="R -> H (in AH5; 30% 17alpha-hydroxylase activity and
FT 29% 17,20-lyase activity; dbSNP:rs763398879)"
FT /evidence="ECO:0000269|PubMed:10720067"
FT /id="VAR_022757"
FT MUTAGEN 105
FT /note="A->L: Increases the affinity for progesterone,
FT resulting in preferential hydroxylation of progesterone at
FT C17 over C16; increases the catalytic efficiency in the
FT 17,20 lyase reaction."
FT /evidence="ECO:0000269|PubMed:25301938"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:6WW0"
FT HELIX 49..60
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 79..86
FT /evidence="ECO:0007829|PDB:6WR1"
FT TURN 87..93
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 100..105
FT /evidence="ECO:0007829|PDB:6WR1"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:5UYS"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:6WW0"
FT HELIX 142..159
FT /evidence="ECO:0007829|PDB:6WR1"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6WW0"
FT HELIX 168..184
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 193..208
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 228..251
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:6WR0"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 289..320
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 322..335
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 344..348
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 351..363
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 391..394
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 396..400
FT /evidence="ECO:0007829|PDB:6WR1"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:6WW0"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 445..462
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 463..466
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:6CIR"
FT STRAND 479..485
FT /evidence="ECO:0007829|PDB:6WR1"
FT STRAND 491..495
FT /evidence="ECO:0007829|PDB:6WR1"
FT HELIX 497..500
FT /evidence="ECO:0007829|PDB:6WR1"
SQ SEQUENCE 508 AA; 57371 MW; E5454E9E18F96B0E CRC64;
MWELVALLLL TLAYLFWPKR RCPGAKYPKS LLSLPLVGSL PFLPRHGHMH NNFFKLQKKY
GPIYSVRMGT KTTVIVGHHQ LAKEVLIKKG KDFSGRPQMA TLDIASNNRK GIAFADSGAH
WQLHRRLAMA TFALFKDGDQ KLEKIICQEI STLCDMLATH NGQSIDISFP VFVAVTNVIS
LICFNTSYKN GDPELNVIQN YNEGIIDNLS KDSLVDLVPW LKIFPNKTLE KLKSHVKIRN
DLLNKILENY KEKFRSDSIT NMLDTLMQAK MNSDNGNAGP DQDSELLSDN HILTTIGDIF
GAGVETTTSV VKWTLAFLLH NPQVKKKLYE EIDQNVGFSR TPTISDRNRL LLLEATIREV
LRLRPVAPML IPHKANVDSS IGEFAVDKGT EVIINLWALH HNEKEWHQPD QFMPERFLNP
AGTQLISPSV SYLPFGAGPR SCIGEILARQ ELFLIMAWLL QRFDLEVPDD GQLPSLEGIP
KVVFLIDSFK VKIKVRQAWR EAQAEGST
