ID   CP17A_PAPHU             Reviewed;         508 AA.
AC   Q9GLD2; Q95M62;
DT   28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 97.
DE   RecName: Full=Steroid 17-alpha-hydroxylase/17,20 lyase;
DE            EC=1.14.14.19 {ECO:0000269|PubMed:12423360};
DE            EC=1.14.14.32 {ECO:0000269|PubMed:12423360};
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   Papio hamadryas ursinus (Chacma baboon).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Papio.
OX   NCBI_TaxID=36229;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Adrenal gland;
RA   Swart A.C., Kolar N.W., Swart P.;
RT   "Cloning and expression of baboon cytochrome P-450 17-alpha
RT   hydroxylase/c17-20 lyase.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12423360; DOI=10.1046/j.1432-1033.2002.03268.x;
RA   Swart A.C., Kolar N.W., Lombard N., Mason J.I., Swart P.;
RT   "Baboon cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17).";
RL   Eur. J. Biochem. 269:5608-5616(2002).
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 (PubMed:12423360). A second
CC       oxidative step, required only for androgen synthesis, involves an acyl-
CC       carbon cleavage. Hydroxylates pregnenolone to form 17-alpha
CC       pregnenolone, followed by the cleavage of the C17-C20 bond to form
CC       dehydroepiandrosterone (DHEA) (PubMed:12423360). Has 17-alpha
CC       hydroxylase activity toward progesterone (PubMed:12423360). The 17-
CC       alpha hydroxy intermediates, as part of adrenal glucocorticoids
CC       biosynthesis pathway, are precursors of cortisol. 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) (By similarity). {ECO:0000250|UniProtKB:P05093,
CC       ECO:0000269|PubMed:12423360}.
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-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   -!- 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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF297650; AAG10599.1; -; mRNA.
DR   EMBL; AY034635; AAK57726.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9GLD2; -.
DR   SMR; Q9GLD2; -.
DR   BRENDA; 1.14.14.19; 4524.
DR   UniPathway; UPA00788; -.
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   1: Evidence at protein level;
KW   Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Lyase; Membrane;
KW   Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Steroidogenesis.
FT   CHAIN           1..508
FT                   /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT                   /id="PRO_0000051938"
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"
FT   CONFLICT        331
FT                   /note="G -> E (in Ref. 2; AAK57726)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        396
FT                   /note="L -> R (in Ref. 2; AAK57726)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   508 AA;  57566 MW;  40DF6068D66BAA80 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 KEKFRSDSIT NMLDVLMQAK MNSDNGNAGP DQDSELLSDN HILTTIGDIF
     GAGVETTTSV VKWIVAFLLH NPQVKKKLYE GIDQNVGFSR TPTISDRNRL LLLEATIREV
     LRIRPVAPML IPHKANVDSS IGEFAVDKGT HVIINLWALH HNEKEWHQPD QFMPERFLNP
     AGTQLISPSL SYLPFGAGPR SCIGEILARQ ELFLIMAWLL QRFDLEVPDD GQLPSLEGNP
     KVVFLIDSFK VKIKVRQAWR EAQAEGST
//