CP11A_CAPHI
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 03-AUG-2022, entry version 109.
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}.
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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; ENSCHIP00000025336; ENSCHIG00000022151.
DR GeneID; 102173131; -.
DR KEGG; chx:102173131; -.
DR CTD; 1583; -.
DR VGNC; VGNC:103462; CYP11A1.
DR GeneTree; ENSGT00940000158575; -.
DR OrthoDB; 561463at2759; -.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000291000; Chromosome 21.
DR Bgee; ENSCHIG00000022151; Expressed in adrenal gland and 11 other 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; -; 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..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
