CP17A_MOUSE
ID CP17A_MOUSE Reviewed; 507 AA.
AC P27786;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 170.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1840559; DOI=10.1016/0888-7543(91)90511-c;
RA Youngblood G.L., Sartorius C., Taylor B.A., Payne A.H.;
RT "Isolation, characterization, and chromosomal mapping of mouse P450 17
RT alpha-hydroxylase/C17-20 lyase.";
RL Genomics 10:270-275(1991).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; M64863; AAA39877.1; -; mRNA.
DR CCDS; CCDS29882.1; -.
DR PIR; A39072; A39072.
DR RefSeq; NP_031835.3; NM_007809.3.
DR AlphaFoldDB; P27786; -.
DR SMR; P27786; -.
DR BioGRID; 198999; 11.
DR STRING; 10090.ENSMUSP00000026012; -.
DR iPTMnet; P27786; -.
DR PhosphoSitePlus; P27786; -.
DR SwissPalm; P27786; -.
DR jPOST; P27786; -.
DR PaxDb; P27786; -.
DR PeptideAtlas; P27786; -.
DR PRIDE; P27786; -.
DR ProteomicsDB; 283614; -.
DR Antibodypedia; 31491; 646 antibodies from 40 providers.
DR DNASU; 13074; -.
DR Ensembl; ENSMUST00000026012; ENSMUSP00000026012; ENSMUSG00000003555.
DR GeneID; 13074; -.
DR KEGG; mmu:13074; -.
DR UCSC; uc008hua.2; mouse.
DR CTD; 1586; -.
DR MGI; MGI:88586; Cyp17a1.
DR VEuPathDB; HostDB:ENSMUSG00000003555; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000155588; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; P27786; -.
DR OMA; GPQEAME; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P27786; -.
DR TreeFam; TF105095; -.
DR Reactome; R-MMU-193048; Androgen biosynthesis.
DR Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR UniPathway; UPA00788; -.
DR BioGRID-ORCS; 13074; 2 hits in 75 CRISPR screens.
DR PRO; PR:P27786; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P27786; protein.
DR Bgee; ENSMUSG00000003555; Expressed in gonadal ridge and 38 other tissues.
DR ExpressionAtlas; P27786; baseline and differential.
DR Genevisible; P27786; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IDA:MGI.
DR GO; GO:0042446; P:hormone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; ISO:MGI.
DR GO; GO:0042448; P:progesterone metabolic process; ISS:UniProtKB.
DR GO; GO:0006694; P:steroid biosynthetic process; ISO:MGI.
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 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Lyase; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroidogenesis.
FT CHAIN 1..507
FT /note="Steroid 17-alpha-hydroxylase/17,20 lyase"
FT /id="PRO_0000051935"
FT BINDING 441
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 507 AA; 57638 MW; C0916193356EFEBD CRC64;
MWELVGLLLL ILAYFFWPKS KTPNAKFPRS LPFLPLVGSL PFLPRRGHMH ANFFKLQEKY
GPIYSLRLGT TTAVIVGHYQ LAREVLVKKG KEFSGRPQMV TLGLLSDQGK GVAFADSSSS
WQLHRKLVFS TFSLFRDDQK LEKMICQEAN SLCDLILTYD GESRDLSTLI FKSVINIICT
ICFNISFENK DPILTTIQTF TEGIVDVLGH SDLVDIFPWL KIFPNKNLEM IKEHTKIREK
TLVEMFEKCK EKFNSESLSS LTDILIQAKM NAENNNTGEG QDPSVFSDKH ILVTVGDIFG
AGIETTSSVL NWILAFLVHN PEVKRKIQKE IDQYVGFSRT PSFNDRTHLL MLEATIREVL
RIRPVAPLLI PHKANIDSSI GEFAIPKDTH VIINLWALHH DKNEWDQPDR FMPERFLDPT
GSHLITPTPS YLPFGAGPRS CIGEALARQE LFIFMALLLQ RFDFDVSDDK QLPCLVGDPK
VVFLIDPFKV KITVRQAWKD AQVEVST
