ID   CP17A_MACFA             Reviewed;         508 AA.
AC   Q2XVA1;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2005, sequence version 1.
DT   27-MAR-2024, entry version 83.
DE   RecName: Full=Steroid 17-alpha-hydroxylase/17,20 lyase;
DE            EC=1.14.14.19 {ECO:0000250|UniProtKB:P05093};
DE   AltName: Full=17-alpha-hydroxyprogesterone aldolase;
DE            EC=1.14.14.32 {ECO:0000250|UniProtKB:P05093};
DE   AltName: Full=CYPXVII;
DE   AltName: Full=Cytochrome P450 17A1;
DE   AltName: Full=Cytochrome P450-C17;
DE            Short=Cytochrome P450c17;
DE   AltName: Full=Steroid 17-alpha-monooxygenase;
GN   Name=CYP17A1; Synonyms=CYP17;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Liu H., Larbie F., Luu-The V.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in corticoid and
CC       androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21
CC       steroids, which is common for both pathways. A second oxidative step,
CC       required only for androgen synthesis, involves an acyl-carbon cleavage.
CC       The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids
CC       biosynthesis pathway, are precursors of cortisol. 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. Has 16-
CC       alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-
CC       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. Mechanistically, uses
CC       molecular oxygen inserting one oxygen atom into a substrate, and
CC       reducing the second into a water molecule, with two electrons provided
CC       by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein
CC       reductase). {ECO:0000250|UniProtKB:P05093}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a C21-steroid + O2 + reduced [NADPH--hemoprotein reductase] =
CC         a 17alpha-hydroxy-C21-steroid + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:65760, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210, ChEBI:CHEBI:61313, ChEBI:CHEBI:138141;
CC         EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65761;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC         17alpha-hydroxyprogesterone + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46308, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17026,
CC         ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC         EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46309;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + pregnenolone + reduced [NADPH--hemoprotein reductase] =
CC         17alpha-hydroxypregnenolone + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50236, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16581,
CC         ChEBI:CHEBI:28750, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC         EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50237;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14754;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53217;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=16alpha,17alpha-dihydroxyprogesterone + O2 + reduced
CC         [NADPH--hemoprotein reductase] = 6beta,16alpha,17alpha-
CC         trihydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:53220, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, 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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53221;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50245;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=16alpha,17alpha-dihydroxypregnenolone + O2 + reduced
CC         [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-
CC         en-17-one + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:53224, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, 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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53225;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced
CC         [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-
CC         en-17-one + 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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47221;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53229;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- ACTIVITY REGULATION: Regulated predominantly by intracellular cAMP
CC       levels. The 17,20-lyase activity is stimulated by cytochrome b5, which
CC       acts as an allosteric effector increasing the Vmax of the lyase
CC       activity. {ECO:0000250|UniProtKB:P05093}.
CC   -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P05093}.
CC   -!- PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis.
CC       {ECO:0000250|UniProtKB:P05093}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P05093}. Microsome membrane
CC       {ECO:0000250|UniProtKB:P05093}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; DQ228167; ABB76808.1; -; mRNA.
DR   RefSeq; NP_001306420.1; NM_001319491.1.
DR   AlphaFoldDB; Q2XVA1; -.
DR   SMR; Q2XVA1; -.
DR   STRING; 9541.ENSMFAP00000004698; -.
DR   BindingDB; Q2XVA1; -.
DR   ChEMBL; CHEMBL3779754; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   OrthoDB; 2900138at2759; -.
DR   UniPathway; UPA00788; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0047442; F:17-alpha-hydroxyprogesterone aldolase activity; ISS:UniProtKB.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004508; F:steroid 17-alpha-monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0006704; P:glucocorticoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0042446; P:hormone biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0042448; P:progesterone metabolic process; ISS:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; ISS:UniProtKB.
DR   CDD; cd20673; CYP17A1; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1.
DR   PANTHER; PTHR24289:SF13; STEROID 17-ALPHA-HYDROXYLASE_17,20 LYASE; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Lyase; Membrane;
KW   Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Steroidogenesis.
FT   CHAIN           1..508
FT                   /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT                   /id="PRO_0000051932"
FT   BINDING         202
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05093"
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                   /evidence="ECO:0000250"
SQ   SEQUENCE   508 AA;  57619 MW;  92D7FFDF81398063 CRC64;
     MWELVALLLL TLAYLFWPKR RCPGAKYPKS LLSLPLVGSL PFLPRHGHMH NNFFKLQKKY
     GPIYSVRMGT KTTVIVGHHQ LAKEVLIKKG KDFSGRPQVT TLDILSNNRK GIAFADYGAH
     WQLHRRLAMA TFALFKDGDQ KLEKIICQEI STLCDMLATH NGQTIDISFP VFVAITNVIS
     LICFNISYKN GDPELKIVHN YNEGIIDSLG KESLVDLFPW LKVFPNKTLE KLKRHVKTRN
     DLLTKIFENY KEKFHSDSIT NMLDVLMQAK MNSDNGNAGP DQDSELLSDN HILTTIGDIF
     GAGVETTTSV VKWIVAFLLH NPQVKKKLYE EIDQNVGFSR TPTISDRNRL LLLEATIREV
     LRIRPVAPML IPHKANVDSS IGEFAVDKGT HVIINLWALH HNEKEWHQPD QFMPERFLNP
     AGTQLISPSL SYLPFGAGPR SCIGEILARQ ELFLIMAWLL QRFDLEVPDD GQLPSLEGNP
     KVVFLIDSFK VKIKVRQAWR EAQAEGST
//