CP11A_MACFA
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 03-AUG-2022, entry version 70.
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}.
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DR EMBL; DQ228169; ABB76810.1; -; mRNA.
DR RefSeq; NP_001271838.1; NM_001284909.1.
DR AlphaFoldDB; Q2XV99; -.
DR SMR; Q2XV99; -.
DR STRING; 9541.XP_005560121.1; -.
DR PRIDE; Q2XV99; -.
DR GeneID; 102120640; -.
DR CTD; 1583; -.
DR eggNOG; KOG0159; Eukaryota.
DR OrthoDB; 561463at2759; -.
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; -; 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 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
