ID CP11A_CAPHI Reviewed; 520 AA. AC P79153; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 113. 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 {ECO:0000303|PubMed:8645627}; OS Capra hircus (Goat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Caprinae; Capra. OX NCBI_TaxID=9925; 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). 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}. 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; D50058; BAA08776.1; -; mRNA. DR RefSeq; NP_001274503.1; NM_001287574.1. DR AlphaFoldDB; P79153; -. DR SMR; P79153; -. DR STRING; 9925.ENSCHIP00000025336; -. DR Ensembl; ENSCHIT00000033198.1; ENSCHIP00000025336.1; ENSCHIG00000022151.1. DR GeneID; 102173131; -. DR KEGG; chx:102173131; -. DR CTD; 1583; -. DR VGNC; VGNC:103462; CYP11A1. DR GeneTree; ENSGT00940000158575; -. DR OrthoDB; 2658719at2759; -. DR UniPathway; UPA00229; -. DR UniPathway; UPA00296; -. DR Proteomes; UP000291000; Chromosome 21. DR Proteomes; UP000694566; Unplaced. DR Proteomes; UP000694900; Genome assembly. DR Bgee; ENSCHIG00000022151; Expressed in adrenal gland and 11 other cell types or tissues. 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 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..520 FT /note="Cholesterol side-chain cleavage enzyme, FT mitochondrial" FT /id="PRO_0000003583" FT REGION 27..48 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; 60418 MW; 4FB09A3C89310317 CRC64; MLARGLPLRS ALVKACPPLL NTGREGWGHH RVGTGEGAGI STRTPRPYSE IPSPGDNGWI NLYHFWRKKS SQRIHFRHIE NFQKYGPIYR EKLGNLESVY IIHPEDVAHL FKFEGSYPQR YDIPPWLAYH QYYQKPIGVL FKKSGAWKKD RVVLNTEVMA PEAIKNFIPL LNPVSQDFVS LLRKRIQQQG SGKFAGDIKE DLFHFAFESI TNVMFGERLG MLEDTVNTEA QKFIDAVYKM FHTSVPLLNL PPELYRLFRT KTWRDHVAAW DTIFNKAEKY TEIFYQDLRQ KTEFRNYPGI LYHLLKSEKM LLEDVKANIT EMLAGGVDTT SMTLQWHLYE MARSLNVQEM LREEVLNARR QAEGDISKML QMVPLLKASI KETLRLHPIS VTLQRYPESD LVLQDYLIPA KTLVQVAIYA MGRDPAFFSN PDKFDPTRWL GKDKDLIHFR NLGFGWGVRQ CVGRRIAELE MTLFLIHILE NFKIEMQQIG DVNTIFNLIL TPDKPIFLVF RPFNQDPPQA //