ID   CP11A_RABIT             Reviewed;         445 AA.
AC   Q28827;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-NOV-2023, entry version 112.
DE   RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000303|PubMed:7682938};
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; Fragment;
GN   Name=CYP11A1;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7682938; DOI=10.1210/endo.132.5.7682938;
RA   Yang X., Iwamoto K., Wang M., Artwohl J., Mason J.I., Pang S.;
RT   "Inherited congenital adrenal hyperplasia in the rabbit is caused by a
RT   deletion in the gene encoding cytochrome P450 cholesterol side-chain
RT   cleavage enzyme.";
RL   Endocrinology 132:1977-1982(1993).
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; S59219; AAB26372.1; -; mRNA.
DR   PIR; A49189; A49189.
DR   AlphaFoldDB; Q28827; -.
DR   SMR; Q28827; -.
DR   STRING; 9986.ENSOCUP00000023976; -.
DR   PaxDb; 9986-ENSOCUP00000023976; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   InParanoid; Q28827; -.
DR   UniPathway; UPA00229; -.
DR   UniPathway; UPA00296; -.
DR   Proteomes; UP000001811; 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; IPR002399; Cyt_P450_mitochondrial.
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; PR00408; MITP450.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; 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..>445
FT                   /note="Cholesterol side-chain cleavage enzyme,
FT                   mitochondrial"
FT                   /id="PRO_0000003589"
FT   NON_TER         1
FT   NON_TER         445
SQ   SEQUENCE   445 AA;  51016 MW;  B6080DFFB028C8CA CRC64;
     RGLPSRSVFL RGCQASLSTA QERLGHPGVP TREGVRVATR SPRPYHEIPS PGDNGWLNLY
     HLAEEKGTHR VHYRHVQNFQ KYGPIYRENL GNVESVYIMD PEDVALLFNS EGPQPERFLI
     PPWVAYHEYY RRPVGVLLKK AQGWKRDRVA LNQEVMAPDA IKNFVPLLEA VSQAFVRMLH
     GRVQQGVFSG DISDDLFRFA FESMTNIMFG ERLGMLEETV DPEAHEFIDA VYQMFHTSVP
     MLSLPPSLFR LFRTRTWRDH VAAWDVIFTN ADKYTQSFYW DLRQKQDLGG SYRGILYSLL
     GTSKLSFEDI KANVTEMLAG SVDTTSMTLQ WHLYEMGAAL GMQEMLRAEV LAARRQAQGD
     MTAMLQSVPL LKASIKETLR LHPISVTLQR YLVNDLVLQD YMIPAKTLVQ VANYGMGREP
     SFFANPEKFD PPRWLDKDKN ATHFR
//