CP11A_SHEEP
ID CP11A_SHEEP Reviewed; 520 AA.
AC P79202;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 107.
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 {ECO:0000303|PubMed:7948001};
DE AltName: Full=Cholesterol desmolase;
DE AltName: Full=Cytochrome P450 11A1;
DE AltName: Full=Cytochrome P450(scc);
DE Flags: Precursor;
GN Name=CYP11A1 {ECO:0000303|PubMed:8645627};
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal cortex;
RX PubMed=8645627; DOI=10.1016/0960-0760(95)00263-4;
RA Okuyama E., Okazaki T., Furukawa A., Wu R.-F., Ichikawa Y.;
RT "Molecular cloning and nucleotide sequences of cDNA clones of sheep and
RT goat adrenocortical cytochromes P450scc (CYP11A1).";
RL J. Steroid Biochem. Mol. Biol. 57:179-185(1996).
RN [2]
RP PROTEIN SEQUENCE OF 40-62.
RC TISSUE=Adrenal cortex;
RX PubMed=7948001; DOI=10.1016/0005-2760(94)90108-2;
RA Miyatake A., Tsubaki M., Hori H., Ichikawa Y.;
RT "Purification and comparative characterization of cytochrome P-450scc (CYP
RT XIA1) from sheep adrenocortical mitochondria.";
RL Biochim. Biophys. Acta 1215:176-182(1994).
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 (By similarity). Catalyzes three
CC sequential oxidation reactions of cholesterol, namely the hydroxylation
CC at C22 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 (By similarity).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate and reducing the second into a water molecule. Two electrons
CC are provided by NADPH via a two-protein mitochondrial transfer system
CC comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and
CC nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (By
CC similarity). {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 -!- 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; D50057; BAA08775.1; -; mRNA.
DR RefSeq; NP_001087258.1; NM_001093789.1.
DR AlphaFoldDB; P79202; -.
DR SMR; P79202; -.
DR STRING; 9940.ENSOARP00000004130; -.
DR GeneID; 100048994; -.
DR KEGG; oas:100048994; -.
DR CTD; 1583; -.
DR eggNOG; KOG0159; Eukaryota.
DR OrthoDB; 561463at2759; -.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000002356; 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 1: Evidence at protein level;
KW Cholesterol metabolism; Direct protein sequencing; Heme; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid metabolism; Steroidogenesis; Sterol metabolism;
KW Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7948001"
FT CHAIN 40..520
FT /note="Cholesterol side-chain cleavage enzyme,
FT mitochondrial"
FT /id="PRO_0000003591"
FT REGION 27..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 461
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; 60357 MW; DF8989FB8A87E8AE CRC64;
MLARGLPFRS ALVKACPPLL NTGREGWGHH RVGTGEGAGI STRTPRPYSE IPSPGDNGWI
NLYHFWRKKG SQRIHFHHIE NFQKYGPIYR EKLGNLESVY IIHPEGVAHL FKFEGSYPQR
YDIPPWLAYH RYYQKPIGVL FKKSGAWKKD RVVLNTEVMA PEAIKNFIPL LNPVSQDFVS
LLHKRIKQQG SGKFVGDIKE DLFRFAFESI TNVMFGERLG MLEDTVDTEA QKFIDAVYKM
FHTSVPLLNL PPELYRLFRT KTWRDHVAAW DTIFNKAEKY TEIFYQDLRQ KTEFRNYPGI
LYHLLKSEKM LLEDVKANIT EMLAGGVDTT SMTLQWHLYE MARSLNVQEM LRKEVLNARR
QAEGDISKML QMVPLLKASI KETLRLHPIS VTLQRYPESD LVLQDYLIPA KTLVQVAIYA
MGRDPAFFSN PDKFDPTRWL GKDKDLIHFR NLGFGWGVRQ CVGRRIAELE MTLFLIHILE
NFRVEMQQIG DVNTIFNLIL TPDKPIFLVF RPFNQGPPQA
