ID   CP11A_MACFA             Reviewed;         521 AA.
AC   Q2XV99;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2005, sequence version 1.
DT   24-JAN-2024, entry version 75.
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; Synonyms=CYP11A;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Liu H., Larbie F., Luu-The V.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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}.
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; DQ228169; ABB76810.1; -; mRNA.
DR   RefSeq; NP_001271838.1; NM_001284909.1.
DR   AlphaFoldDB; Q2XV99; -.
DR   SMR; Q2XV99; -.
DR   STRING; 9541.ENSMFAP00000001651; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   OrthoDB; 2658719at2759; -.
DR   UniPathway; UPA00229; -.
DR   UniPathway; UPA00296; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) 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:0006700; P:C21-steroid hormone biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
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; PTHR24279; -; 1.
DR   PANTHER; PTHR24279:SF3; CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME, MITOCHONDRIAL; 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   2: Evidence at transcript 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..39
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P00189"
FT   CHAIN           40..521
FT                   /note="Cholesterol side-chain cleavage enzyme,
FT                   mitochondrial"
FT                   /id="PRO_0000045764"
FT   BINDING         462
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   521 AA;  60242 MW;  91B747E6AC00BA20 CRC64;
     MLAKGLPPRS VLVKGCQTFL SAPKERLGHL RVPTSEGAGI STRSPRPFNE IPSPGDNGWL
     NLYHFWRETG THKVHLHHVQ NFQKYDPIYR EKLGNVESVY VIDPEDVALL FKSEGPNPER
     FLIPPWVAYH QYYQRPIGVL LKKSAAWKKD RVALNQEVMA PETTKNFLPL LDAVSRDFVS
     VLHRRIKKAG SGNFSGDISD DLFRFAFESI TNVIFGERQG MLEEVVNPEG QRFIDAIYQM
     FHTSVHMLNL PPDLFRLFRT KTWKDHVAPR DVIFSKADMY TENFHWELRQ KGNVHHDYRG
     ILYRLLGDSK MSFEDIKANV TEMLAGGVDT TSMTLQWHLY EMARNLKVQD MLRAEVLAAR
     RQAQGDMATI LQLVPLLKAS IKETLRLHPI SVTLQRYLVN DLVLRGYMIP AKTLVQVAIY
     ALGREPTFFF DPENFDPTRW LSKDKNITYF RNLGFGWGVR QCLGRRIAEL EMTIFLINML
     ENFRVEIQHL SDVGTTFNLI LMPEKPISFT FWPFNQEATQ E
//