CP11A_MESAU
ID CP11A_MESAU Reviewed; 520 AA.
AC Q9EPT4;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12093115; DOI=10.1016/s0016-6480(02)00003-5;
RA Vilchis F., Chavez B., Larrea F., Timossi C., Montiel F.;
RT "The cDNA cloning and tissue expression of the cytochrome P450scc from
RT Syrian hamster (Mesocricetus auratus).";
RL Gen. Comp. Endocrinol. 126:279-286(2002).
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; AF323965; AAG42320.1; -; mRNA.
DR RefSeq; NP_001268569.1; NM_001281640.1.
DR AlphaFoldDB; Q9EPT4; -.
DR SMR; Q9EPT4; -.
DR STRING; 10036.XP_005069662.1; -.
DR PRIDE; Q9EPT4; -.
DR GeneID; 101827747; -.
DR eggNOG; KOG0159; Eukaryota.
DR OrthoDB; 561463at2759; -.
DR BRENDA; 1.14.15.6; 3239.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000189706; 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..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P00189"
FT CHAIN 37..520
FT /note="Cholesterol side-chain cleavage enzyme,
FT mitochondrial"
FT /id="PRO_0000003586"
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 520 AA; 60271 MW; 648C5A82D0D41D1E CRC64;
MLAKGLSLRS VLAKGCQPFL SPTWQSSVLA TGGGANISTN SPRPFNEIPS PGDNGWLNLY
HFWRENGTHR IHYHHMQNFQ KYGPIYREKL GNKDSVYILD PEDAAQLFLS EGPYPERYLV
PPWVAYHQYY KRPIGVLFKS SEAWKKDRLV LNQEVMAPEA IKNFVPLLEG VVQDFINVLH
RRIKQQKSGN FSGDISDDLF RFAFESITSV VFGERLGMLE EIVDPESQRF IDAIYQMFHT
SVPMLNLPPE LFRFFRTKTW KEHAAAWDMI FKKADDYTQT FYWDLRQKQE FSKYPGVLYS
LLGGNKLPFK NIQANITEML AGGVDTTSMT LQWSLYEMAH NLKVQEMLRA EVLAARRQAQ
GDMVKMVQLV PLLKASIKET LRLHPISVTV QRYLVDDLVL RNYRIPAKML VQVANYAMGR
EPSFFPNPNK FDPTRWLEKS KNTTHFRYLS FGWGVRQCLG RRIAELEMTI FLINVLENFR
IELQSLHDVG TKFNLILMPE KPILFNLQPL KKDLGTTTNR
