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 08-NOV-2023, entry version 110. 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}. 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; D50057; BAA08775.1; -; mRNA. DR RefSeq; NP_001087258.1; NM_001093789.1. DR AlphaFoldDB; P79202; -. DR SMR; P79202; -. DR STRING; 9940.ENSOARP00000004130; -. DR PaxDb; 9940-ENSOARP00000004130; -. DR GeneID; 100048994; -. DR KEGG; oas:100048994; -. DR CTD; 1583; -. DR eggNOG; KOG0159; Eukaryota. DR OrthoDB; 2658719at2759; -. 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; 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 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 //