CP11A_BOVIN
ID CP11A_BOVIN Reviewed; 520 AA.
AC P00189; Q28152;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000303|PubMed:3518802};
DE EC=1.14.15.6 {ECO:0000269|PubMed:11412116};
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal cortex;
RX PubMed=6589615; DOI=10.1073/pnas.81.15.4647;
RA Morohashi K., Fujii-Kuriyama Y., Okada Y., Sogawa K., Hirose T.,
RA Inayama S., Omura T.;
RT "Molecular cloning and nucleotide sequence of cDNA for mRNA of
RT mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4647-4651(1984).
RN [2]
RP PROTEIN SEQUENCE OF 40-520.
RX PubMed=3518802; DOI=10.1016/0167-4838(86)90176-7;
RA Chashchin V.L., Lapko V.N., Adamovich T.B., Lapko A.G., Kuprina N.S.,
RA Akhrem A.A.;
RT "Primary structure of the cholesterol side-chain cleavage cytochrome P-450
RT from bovine adrenocortical mitochondria and some aspects of its functioning
RT on a structural level.";
RL Biochim. Biophys. Acta 871:217-223(1986).
RN [3]
RP PROTEIN SEQUENCE OF 40-54.
RX PubMed=6654880;
RA Ogishima T., Okada Y., Kominami S., Takemori S., Omura T.;
RT "Partial amino acid sequences of two mitochondrial and two microsomal
RT cytochrome P-450's from adrenal cortex.";
RL J. Biochem. 94:1711-1714(1983).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-90.
RX PubMed=2154474; DOI=10.1016/s0021-9258(19)39768-6;
RA Ahlgren R., Simpson E.R., Waterman M.R., Lund J.;
RT "Characterization of the promoter/regulatory region of the bovine CYP11A
RT (P-450scc) gene. Basal and cAMP-dependent expression.";
RL J. Biol. Chem. 265:3313-3319(1990).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=3011431; DOI=10.1111/j.1432-1033.1986.tb09633.x;
RA Hanukoglu I., Hanukoglu Z.;
RT "Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and
RT adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for
RT membrane organization and gene regulation.";
RL Eur. J. Biochem. 157:27-31(1986).
RN [6]
RP 3D-STRUCTURE MODELING OF 40-520.
RX PubMed=1477100; DOI=10.1016/0167-4838(92)90089-v;
RA Vijayakumar S., Salerno J.C.;
RT "Molecular modeling of the 3-D structure of cytochrome P-450scc.";
RL Biochim. Biophys. Acta 1160:281-286(1992).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-233, AND PATHWAY.
RX PubMed=11412116; DOI=10.1021/bi010193i;
RA Pikuleva I.A., Puchkaev A., Bjoerkhem I.;
RT "Putative helix F contributes to regioselectivity of hydroxylation in
RT mitochondrial cytochrome P450 27A1.";
RL Biochemistry 40:7621-7629(2001).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 41-520 IN COMPLEX WITH HEME AND
RP 22R-HYDROXYCHOLESTEROL, AND COFACTOR.
RX PubMed=21159775; DOI=10.1074/jbc.m110.188433;
RA Mast N., Annalora A.J., Lodowski D.T., Palczewski K., Stout C.D.,
RA Pikuleva I.A.;
RT "Structural basis for three-step sequential catalysis by the cholesterol
RT side chain cleavage enzyme CYP11A1.";
RL J. Biol. Chem. 286:5607-5613(2011).
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 (PubMed:11412116). 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 (PubMed:11412116).
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)
CC (PubMed:11412116). {ECO:0000269|PubMed:11412116}.
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:0000269|PubMed:11412116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740;
CC Evidence={ECO:0000305|PubMed:11412116};
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:0000269|PubMed:11412116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336;
CC Evidence={ECO:0000305|PubMed:11412116};
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:0000269|PubMed:11412116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340;
CC Evidence={ECO:0000305|PubMed:11412116};
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:0000269|PubMed:11412116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344;
CC Evidence={ECO:0000305|PubMed:11412116};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:21159775};
CC -!- PATHWAY: Lipid metabolism; C21-steroid hormone metabolism.
CC {ECO:0000269|PubMed:11412116}.
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:11412116}.
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 -!- TISSUE SPECIFICITY: Detected in adrenal cortex and corpus luteum (at
CC protein level). {ECO:0000269|PubMed:3011431}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; K02130; AAA30488.1; -; mRNA.
DR EMBL; J05245; AAA30681.1; -; Genomic_DNA.
DR PIR; A00189; O4BOM.
DR RefSeq; NP_788817.1; NM_176644.2.
DR PDB; 3MZS; X-ray; 2.50 A; A/B/C/D=41-520.
DR PDBsum; 3MZS; -.
DR AlphaFoldDB; P00189; -.
DR SMR; P00189; -.
DR STRING; 9913.ENSBTAP00000009106; -.
DR BindingDB; P00189; -.
DR ChEMBL; CHEMBL4813; -.
DR DrugCentral; P00189; -.
DR PaxDb; P00189; -.
DR GeneID; 338048; -.
DR KEGG; bta:338048; -.
DR CTD; 1583; -.
DR eggNOG; KOG0159; Eukaryota.
DR InParanoid; P00189; -.
DR OrthoDB; 561463at2759; -.
DR BRENDA; 1.14.15.6; 908.
DR SABIO-RK; P00189; -.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR PRO; PR:P00189; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0042359; P:vitamin D metabolic process; IDA: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 3D-structure; Cholesterol metabolism; Direct protein sequencing; Heme;
KW Iron; 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:3518802,
FT ECO:0000269|PubMed:6654880"
FT CHAIN 40..520
FT /note="Cholesterol side-chain cleavage enzyme,
FT mitochondrial"
FT /id="PRO_0000003582"
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:0000269|PubMed:21159775,
FT ECO:0007744|PDB:3MZS"
FT MUTAGEN 233
FT /note="F->A: Impairs the hydroxylase activity toward
FT cholesterol; increases the electron leakage from the
FT electron transfer chain."
FT /evidence="ECO:0000269|PubMed:11412116"
FT MUTAGEN 233
FT /note="F->K: Markedly reduces the hydroxylase activity
FT toward cholesterol."
FT /evidence="ECO:0000269|PubMed:11412116"
FT CONFLICT 22
FT /note="T -> S (in Ref. 4; AAA30681)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 58..68
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 74..85
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 104..112
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:3MZS"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:3MZS"
FT TURN 161..167
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 168..189
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 199..215
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 243..247
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 260..289
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 300..306
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 312..343
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 345..355
FT /evidence="ECO:0007829|PDB:3MZS"
FT TURN 356..362
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 366..369
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 374..386
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 401..408
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 418..423
FT /evidence="ECO:0007829|PDB:3MZS"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 436..440
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:3MZS"
FT HELIX 464..479
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 485..488
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 494..504
FT /evidence="ECO:0007829|PDB:3MZS"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:3MZS"
SQ SEQUENCE 520 AA; 60333 MW; 81C84B4AE0E70418 CRC64;
MLARGLPLRS ALVKACPPIL STVGEGWGHH RVGTGEGAGI STKTPRPYSE IPSPGDNGWL
NLYHFWREKG SQRIHFRHIE NFQKYGPIYR EKLGNLESVY IIHPEDVAHL FKFEGSYPER
YDIPPWLAYH RYYQKPIGVL FKKSGTWKKD RVVLNTEVMA PEAIKNFIPL LNPVSQDFVS
LLHKRIKQQG SGKFVGDIKE DLFHFAFESI TNVMFGERLG MLEETVNPEA QKFIDAVYKM
FHTSVPLLNV PPELYRLFRT KTWRDHVAAW DTIFNKAEKY TEIFYQDLRR KTEFRNYPGI
LYCLLKSEKM LLEDVKANIT EMLAGGVNTT SMTLQWHLYE MARSLNVQEM LREEVLNARR
QAEGDISKML QMVPLLKASI KETLRLHPIS VTLQRYPESD LVLQDYLIPA KTLVQVAIYA
MGRDPAFFSS PDKFDPTRWL SKDKDLIHFR NLGFGWGVRQ CVGRRIAELE MTLFLIHILE
NFKVEMQHIG DVDTIFNLIL TPDKPIFLVF RPFNQDPPQA
