CP11A_MOUSE
ID CP11A_MOUSE Reviewed; 526 AA.
AC Q9QZ82;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000250|UniProtKB:P05108};
DE EC=1.14.15.6 {ECO:0000250|UniProtKB:P05108};
DE AltName: Full=CYPXIA1;
DE AltName: Full=Cholesterol desmolase;
DE AltName: Full=Cytochrome P450 11A1;
DE AltName: Full=Cytochrome P450(scc);
DE Flags: Precursor;
GN Name=Cyp11a1 {ECO:0000312|MGI:MGI:88582}; Synonyms=Cyp11a;
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].
RC STRAIN=C57BL/6J;
RA Tanaka M., Hennebold J.H., Adashi E.Y.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
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 that catalyzes the side-chain
CC hydroxylation and cleavage of cholesterol to pregnenolone, the
CC precursor of most steroid hormones. Catalyzes three sequential
CC oxidation reactions of cholesterol, namely the hydroxylation at C22
CC followed with the hydroxylation at C20 to yield 20R,22R-
CC hydroxycholesterol that is further cleaved between C20 and C22 to yield
CC the C21-steroid pregnenolone and 4-methylpentanal. Mechanistically,
CC uses molecular oxygen inserting one oxygen atom into a substrate and
CC reducing the second into a water molecule. Two electrons are provided
CC by NADPH via a two-protein mitochondrial transfer system comprising
CC flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-
CC sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).
CC {ECO:0000250|UniProtKB:P05108}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + 6 H(+) + 3 O2 + 6 reduced [adrenodoxin] = 4-
CC methylpentanal + 4 H2O + 6 oxidized [adrenodoxin] + pregnenolone;
CC Xref=Rhea:RHEA:35739, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.6;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (22R)-
CC hydroxycholesterol + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:34335, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:67237; Evidence={ECO:0000250|UniProtKB:P05108};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(22R)-hydroxycholesterol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:34339, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:67237;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20R,22R)-20,22-dihydroxycholesterol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 4-methylpentanal + 2 H2O + 2 oxidized [adrenodoxin] +
CC pregnenolone; Xref=Rhea:RHEA:34343, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P05108};
CC -!- PATHWAY: Lipid metabolism; C21-steroid hormone metabolism.
CC {ECO:0000250|UniProtKB:P05108}.
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000250|UniProtKB:P05108}.
CC -!- SUBUNIT: Interacts with FDX1/adrenodoxin.
CC {ECO:0000250|UniProtKB:P05108}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion
CC inner membrane. {ECO:0000250|UniProtKB:P14137}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF195119; AAF03897.1; -; mRNA.
DR CCDS; CCDS40653.1; -.
DR RefSeq; NP_062753.3; NM_019779.4.
DR AlphaFoldDB; Q9QZ82; -.
DR SMR; Q9QZ82; -.
DR BioGRID; 198997; 1.
DR STRING; 10090.ENSMUSP00000034874; -.
DR PhosphoSitePlus; Q9QZ82; -.
DR MaxQB; Q9QZ82; -.
DR PaxDb; Q9QZ82; -.
DR PRIDE; Q9QZ82; -.
DR ProteomicsDB; 283805; -.
DR Antibodypedia; 3076; 440 antibodies from 32 providers.
DR Ensembl; ENSMUST00000034874; ENSMUSP00000034874; ENSMUSG00000032323.
DR GeneID; 13070; -.
DR KEGG; mmu:13070; -.
DR UCSC; uc009pwa.1; mouse.
DR CTD; 1583; -.
DR MGI; MGI:88582; Cyp11a1.
DR VEuPathDB; HostDB:ENSMUSG00000032323; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00940000158575; -.
DR HOGENOM; CLU_001570_28_4_1; -.
DR InParanoid; Q9QZ82; -.
DR OMA; MPDKPIF; -.
DR OrthoDB; 561463at2759; -.
DR PhylomeDB; Q9QZ82; -.
DR TreeFam; TF105094; -.
DR Reactome; R-MMU-196108; Pregnenolone biosynthesis.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR BioGRID-ORCS; 13070; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9QZ82; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9QZ82; protein.
DR Bgee; ENSMUSG00000032323; Expressed in adrenal gland and 62 other tissues.
DR ExpressionAtlas; Q9QZ82; baseline and differential.
DR Genevisible; Q9QZ82; MM.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0015485; F:cholesterol binding; ISO:MGI.
DR GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; IDA:MGI.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:MGI.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0007617; P:mating behavior; ISO:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0006694; P:steroid biosynthetic process; ISO:MGI.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR033283; CYP11A1.
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; PTHR24279:SF3; PTHR24279:SF3; 1.
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 Cholesterol metabolism; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Steroidogenesis;
KW Sterol metabolism; Transit peptide.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P00189"
FT CHAIN 37..526
FT /note="Cholesterol side-chain cleavage enzyme,
FT mitochondrial"
FT /id="PRO_0000003587"
FT REGION 30..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 458
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|UniProtKB:P05108"
SQ SEQUENCE 526 AA; 60315 MW; E5029738EE4ECB71 CRC64;
MLAKGLSLRS VLVKGCQPFL SPTWQGPVLS TGKGAGTSTS SPRSFNEIPS PGDNGWLNLY
HFWRESGTQK IHYHQMQSFQ KYGPIYREKL GTLESVYIVD PKDASILFSC EGPNPERFLV
PPWVAYHQYY QRPIGVLFKS SDAWKKDRIV LNQEVMAPGA IKNFVPLLEG VAQDFIKVLH
RRIKQQNSGN FSGVISDDLF RFSFESISSV IFGERMGMLE EIVDPEAQRF INAVYQMFHT
SVPMLNLPPD FFRLLRTKTW KDHAAAWDVI FNKADEYTQN FYWDLRQKRD FSQYPGVLYS
LLGGNKLPFK NIQANITEML AGGVDTTSMT LQWNLYEMAH NLKVQEMLRA EVLAARRQAQ
GDMAKMVQLV PLLKASIKET LRLHPISVTL QRYTVNDLVL RNYKIPAKTL VQVASFAMGR
DPGFFPNPNK FDPTRWLEKS QNTTHFRYLG FGWGVRQCLG RRIAELEMTI LLINLLENFR
IEVQNLRDVG TKFSLILMPE NPILFNFQPL KQDLGPAVTR KDNTVN
