CP11A_PIG
ID CP11A_PIG Reviewed; 520 AA.
AC P10612;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000250|UniProtKB:P05108};
DE EC=1.14.15.6 {ECO:0000269|PubMed:1773895, ECO:0000269|PubMed:2039527};
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=2922297; DOI=10.1093/nar/17.4.1773;
RA Mulheron G.W., Stone R.T., Miller W.L., Wise T.H.;
RT "Nucleotide sequence of cytochrome P-450 cholesterol side-chain cleavage
RT cDNA isolated from porcine testis.";
RL Nucleic Acids Res. 17:1773-1773(1989).
RN [2]
RP PROTEIN SEQUENCE OF 41-61, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Testis;
RX PubMed=2039527; DOI=10.1016/0006-291x(91)90457-i;
RA Kuwada M., Kitajima R., Suzuki H., Horie S.;
RT "Purification and properties of cytochrome P-450 (SCC) from pig testis
RT mitochondria.";
RL Biochem. Biophys. Res. Commun. 176:1501-1508(1991).
RN [3]
RP PROTEIN SEQUENCE OF 40-64, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1773895; DOI=10.1016/0020-711x(91)90078-2;
RA Iwahashi K., Tsubaki M., Miyatake A., Ichikawa Y.;
RT "Purification and comparative characterization of cytochrome P-450scc from
RT porcine adrenocortical mitochondria.";
RL Int. J. Biochem. 23:901-909(1991).
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:1773895, PubMed:2039527).
CC Catalyzes three sequential oxidation reactions of cholesterol, namely
CC the hydroxylation at C22 followed with the hydroxylation at C20 to
CC yield 20R,22R-hydroxycholesterol that is further cleaved between C20
CC and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal
CC (PubMed:1773895, PubMed:2039527). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate and reducing the
CC second into a water molecule. Two electrons are provided by NADPH via a
CC two-protein mitochondrial transfer system comprising flavoprotein FDXR
CC (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1
CC or FDX2 (adrenodoxin/ferredoxin) (PubMed:1773895, PubMed:2039527).
CC {ECO:0000269|PubMed:1773895, ECO:0000269|PubMed:2039527}.
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:1773895, ECO:0000269|PubMed:2039527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740;
CC Evidence={ECO:0000305|PubMed:1773895, ECO:0000305|PubMed:2039527};
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. {ECO:0000250}.
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; X13768; CAA32018.1; -; mRNA.
DR PIR; S03188; S03188.
DR RefSeq; NP_999592.1; NM_214427.1.
DR AlphaFoldDB; P10612; -.
DR SMR; P10612; -.
DR STRING; 9823.ENSSSCP00000023389; -.
DR PaxDb; P10612; -.
DR PeptideAtlas; P10612; -.
DR Ensembl; ENSSSCT00000027131; ENSSSCP00000023389; ENSSSCG00000025273.
DR Ensembl; ENSSSCT00005073357; ENSSSCP00005045971; ENSSSCG00005045389.
DR Ensembl; ENSSSCT00025071481; ENSSSCP00025030963; ENSSSCG00025052195.
DR Ensembl; ENSSSCT00035025514; ENSSSCP00035009655; ENSSSCG00035019678.
DR Ensembl; ENSSSCT00045034038; ENSSSCP00045023617; ENSSSCG00045019950.
DR Ensembl; ENSSSCT00050038177; ENSSSCP00050015825; ENSSSCG00050028382.
DR Ensembl; ENSSSCT00055028793; ENSSSCP00055022943; ENSSSCG00055014425.
DR Ensembl; ENSSSCT00065060792; ENSSSCP00065026328; ENSSSCG00065044449.
DR Ensembl; ENSSSCT00070020379; ENSSSCP00070016933; ENSSSCG00070010472.
DR GeneID; 403329; -.
DR KEGG; ssc:403329; -.
DR CTD; 1583; -.
DR VGNC; VGNC:103363; CYP11A1.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00940000158575; -.
DR HOGENOM; CLU_001570_28_4_1; -.
DR InParanoid; P10612; -.
DR OMA; MPDKPIF; -.
DR OrthoDB; 561463at2759; -.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000008227; Chromosome 7.
DR Proteomes; UP000314985; Chromosome 7.
DR Bgee; ENSSSCG00000025273; Expressed in ovary and 14 other tissues.
DR ExpressionAtlas; P10612; baseline and differential.
DR Genevisible; P10612; SS.
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:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
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:1773895"
FT CHAIN 40..520
FT /note="Cholesterol side-chain cleavage enzyme,
FT mitochondrial"
FT /id="PRO_0000003588"
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"
FT CONFLICT 46
FT /note="R -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 60258 MW; 6C6D0D6FE34F9C33 CRC64;
MLARGLALRS VLVKGCQPFL SAPRECPGHP RVGTGEGACI STKTPRPFSE IPSPGDNGWI
NLYRFWKEKG TQKIHYHHVQ NFQKYGPIYR EKLGNLESVY IIDPEDVALL FKFEGPNPER
YNIPPWVAYH QHYQKPVGVL LKKSGAWKKD RLVLNTEVMA PEAIKNFIPL LDTVSQDFVG
VLHRRIKQQG SGKFSGDIRE DLFRFAFESI TNVIFGERLG MLEEIVDPEA QKFIDAVYQM
FHTSVPMLNL PPDLFRLFRT KTWRDHVAAW DTIFNKAEKY TQNFYWDLRR KREFNNYPGI
LYRLLGNDKL LSEDVKANVT EMLAGGVDTT SMTLQWHLYE MARSLNVQEM LREEVLNARR
QAQGDTSKML QLVPLLKASI KETLRLHPIS VTLQRYLVND LVLRDYMIPA KTLVQVAVYA
MGRDPAFFSN PGQFDPTRWL GKERDLIHFR NLGFGWGVRQ CVGRRIAELE MTLFLIHILE
NFKVELQHFS DVDTIFNLIL MPDKPIFLVF RPFNQDPLQA
