CP17A_SHEEP
ID CP17A_SHEEP Reviewed; 509 AA.
AC Q29497; Q9N0U6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 122.
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 Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal cortex;
RA Murry B.A., Swart P., Mason J.I.;
RT "Cloning and expression of ovine cytochrome P-450 17-alpha hydroxylase/c17-
RT 20 lyase.";
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=12693981; DOI=10.1023/a:1022101703670;
RA Gilep A.A., Estabrook R.W., Usanov S.A.;
RT "Molecular cloning and heterologous expression in E. coli of cytochrome
RT P45017alpha. Comparison of structural and functional properties of
RT substrate-specific cytochromes P450 from different species.";
RL Biochemistry (Mosc.) 68:86-98(2003).
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 [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: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 [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: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 [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: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 [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: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 [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: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 [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: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; L40335; AAA63517.1; -; mRNA.
DR EMBL; AF251388; AAF65824.1; -; mRNA.
DR RefSeq; NP_001009483.1; NM_001009483.1.
DR AlphaFoldDB; Q29497; -.
DR SMR; Q29497; -.
DR STRING; 9940.ENSOARP00000002254; -.
DR GeneID; 493968; -.
DR KEGG; oas:493968; -.
DR CTD; 1586; -.
DR eggNOG; KOG0156; Eukaryota.
DR OrthoDB; 702827at2759; -.
DR BRENDA; 1.14.14.19; 2668.
DR UniPathway; UPA00788; -.
DR Proteomes; UP000002356; 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 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 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..509
FT /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT /id="PRO_0000051942"
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 210
FT /note="G -> S (in Ref. 1; AAA63517)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="N -> Y (in Ref. 1; AAA63517)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 57308 MW; D498E639D36A5148 CRC64;
MWVLLAVFLL TLAYLFWPKT KHSGAKYPRS LPSLPLVGSL PFLPRRGQQH ENFFKLQEKY
GPIYSFRLGS KTTVMIGHHQ LAREVLLKKG KEFSGRPKVA TLDILSDNQK GIAFADHGAH
WQLHRKLVLN AFALFKDGNL KLEKIINQEA NVLCDFLATQ HGQSIDLSEP LSLAVTNIIS
FICFNFSFKN EDPALKAIQN VNDGILEVLG KEVLLDIFPA LKIFPSKAME KMKGCVETRN
ELLSEILEKC QENFTSDSIT NLLHILMQAK VNADNNNTGP EQDSKLLSNR HMLATIADIF
GAGVETTTSV IKWIVAYLLH HPSLKKRIQD SIDQNIGFNR TPTISDRNRL VLLEATIREV
LRIRPVAPML IPHKAIIDSS IGDLTIDKGT DVVVNLWALH HNEKEWQQPD LFMPERFLDP
TGTQLISPSL SYLPFGAGPR SCVGEMLARQ ELFLFMSRLL QRFNLEIPDD GKLPSLEGNP
SLVLQIKPFK VKIEVRQAWK EAQAEGSTS
