ID   CP17A_MESAU             Reviewed;         511 AA.
AC   P70687;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   02-SEP-2026, entry version 129.
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   Mesocricetus auratus (Golden hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Mesocricetus.
OX   NCBI_TaxID=10036;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Adrenal gland;
RX   PubMed=8597469; DOI=10.1111/j.1749-6632.1995.tb17390.x-i1;
RA   Cloutier M., Fleury A., Courtemanche J., Ducharme L., Mason J.I.,
RA   Lehoux J.-G.;
RT   "Cloning and expression of hamster adrenal cytochrome P450C17 cDNA.";
RL   Ann. N. Y. Acad. Sci. 774:294-296(1995).
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 + reduced [NADPH--hemoprotein reductase] + O2 =
CC         a 17alpha-hydroxy-C21-steroid + oxidized [NADPH--hemoprotein
CC         reductase] + H2O + H(+); 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:0000250|UniProtKB:P05093};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65761;
CC         Evidence={ECO:0000250|UniProtKB:P05093};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=progesterone + reduced [NADPH--hemoprotein reductase] + O2 =
CC         17alpha-hydroxyprogesterone + oxidized [NADPH--hemoprotein reductase]
CC         + H2O + H(+); Xref=Rhea:RHEA:46308, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17026, ChEBI:CHEBI:17252, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210; EC=1.14.14.19;
CC         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=pregnenolone + reduced [NADPH--hemoprotein reductase] + O2 =
CC         17alpha-hydroxypregnenolone + oxidized [NADPH--hemoprotein reductase]
CC         + H2O + H(+); Xref=Rhea:RHEA:50236, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16581, ChEBI:CHEBI:28750, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210; EC=1.14.14.19;
CC         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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = androst-4-ene-3,17-dione + acetate + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + 2 H(+); 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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = 16alpha,17alpha-dihydroxyprogesterone + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); 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 + reduced
CC         [NADPH--hemoprotein reductase] + O2 = 6beta,16alpha,17alpha-
CC         trihydroxyprogesterone + oxidized [NADPH--hemoprotein reductase] +
CC         H2O + H(+); 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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = 3beta-hydroxyandrost-5-en-17-one + acetate +
CC         oxidized [NADPH--hemoprotein reductase] + H2O + 2 H(+);
CC         Xref=Rhea:RHEA:50244, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:28689, ChEBI:CHEBI:28750, ChEBI:CHEBI:30089,
CC         ChEBI:CHEBI:57618, 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 + reduced
CC         [NADPH--hemoprotein reductase] + O2 = 3beta,16alpha-dihydroxy-
CC         androst-5-en-17-one + acetate + oxidized [NADPH--hemoprotein
CC         reductase] + H2O + 2 H(+); Xref=Rhea:RHEA:53224, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27771,
CC         ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:137049; 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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = 3beta,16alpha-dihydroxy-androst-5-en-17-one +
CC         oxidized [NADPH--hemoprotein reductase] + H2O + H(+);
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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = 16alpha-hydroxyandrost-4-ene-3,17-dione + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); 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; U66494; AAB07494.1; -; mRNA.
DR   RefSeq; NP_001268860.1; NM_001281931.1.
DR   SMR; P70687; -.
DR   STRING; 10036.ENSMAUP00000015990; -.
DR   GeneID; 101831170; -.
DR   KEGG; maua:101831170; -.
DR   CTD; 1586; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   OrthoDB; 1470350at2759; -.
DR   UniPathway; UPA00788; -.
DR   CDD; cd20673; CYP17A1; 1.
DR   FunFam; 1.10.630.10:FF:000002; Cytochrome P450 1A1; 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.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; 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   Proteomes; UP000886700; Unplaced.
DR   AlphaFoldDB; P70687; -.
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..511
FT                   /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT                   /id="PRO_0000051934"
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   511 AA;  57459 MW;  896E776A7457546C CRC64;
     MWELVALLLL TLAYFFWSKS KTCGAKSPKS LPFLPLVGSL PFIPRHGHPH VNFFKLQEKY
     GPIYSLRLGS TTTVIIGQYQ LAKEVLVKKG KEFSGRPHMV TLGLLSDQGK GIAFADSGGS
     WQLHRKLALS SFALFRDGNQ KLEKIICQKA SSLCDFLLTH NEESIDLSEP IFNSITNIIC
     IICFGISYEN RDPILATIKS FTEGILNSLG NDHLVDIFPW LTIFPNKTVD MIKKNVKIRD
     EVLSGILEKC KEKFNSDSIS SLMDLLIQAK TNADNNNTSE GQGSNAFSDM HILATIADIF
     GAGIETTASV LSWIIAFLLH NPEVKKKIQK EIDQNIGFSR TPTFNDRNHL LMLEATIREV
     LRIRPVAPML IPHRANSDMS IGEFSIPKFT PVIINLWALH HSEKEWDQPD RFMPERFLDP
     TGSHLITPSL SYLPFGAGAR SCIGEVLARQ ELFLFMAHLL QRFDLDVPDD EQPPCLKGNA
     NVVFLIDPFK VKITVRQAWK DAQAEVNTWR P
//