ID   CP11A_RAT               Reviewed;         526 AA.
AC   P14137; Q5FWY8; Q6LDR9;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   08-NOV-2023, entry version 164.
DE   RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000303|PubMed:2176216};
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:21075169}; Synonyms=Cyp11a, Cyp11a-1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2480959; DOI=10.1016/s0021-9258(20)88275-1;
RA   Oonk R.B., Krasnow J.S., Beattie W.G., Richards J.S.;
RT   "Cyclic AMP-dependent and -independent regulation of cholesterol side chain
RT   cleavage cytochrome P-450 (P-450scc) in rat ovarian granulosa cells and
RT   corpora lutea. cDNA and deduced amino acid sequence of rat P-450scc.";
RL   J. Biol. Chem. 264:21934-21942(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2176216; DOI=10.1016/s0021-9258(18)45718-3;
RA   Oonk R.B., Parker K.L., Gibson J.L., Richards J.S.;
RT   "Rat cholesterol side-chain cleavage cytochrome P-450 (P-450scc) gene.
RT   Structure and regulation by cAMP in vitro.";
RL   J. Biol. Chem. 265:22392-22401(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 344-526, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Ovary;
RX   PubMed=3123325; DOI=10.1016/0378-1119(87)90170-3;
RA   McMasters K.M., Dickson L.A., Shamy R.V., Robischon K., Macdonald G.J.,
RA   Moyle W.R.;
RT   "Rat cholesterol side-chain cleavage enzyme (P-450scc): use of a cDNA probe
RT   to study the hormonal regulation of P-450scc mRNA levels in ovarian
RT   granulosa cells.";
RL   Gene 57:1-9(1987).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=3948785; DOI=10.1210/endo-118-4-1353;
RA   Farkash Y., Timberg R., Orly J.;
RT   "Preparation of antiserum to rat cytochrome P-450 cholesterol side chain
RT   cleavage, and its use for ultrastructural localization of the
RT   immunoreactive enzyme by protein A-gold technique.";
RL   Endocrinology 118:1353-1365(1986).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=2170421; DOI=10.1083/jcb.111.4.1373;
RA   Hanukoglu I., Suh B.S., Himmelhoch S., Amsterdam A.;
RT   "Induction and mitochondrial localization of cytochrome P450scc system
RT   enzymes in normal and transformed ovarian granulosa cells.";
RL   J. Cell Biol. 111:1373-1381(1990).
RN   [7]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=21075169; DOI=10.1016/j.mce.2010.10.020;
RA   Pagotto M.A., Roldan M.L., Pagotto R.M., Lugano M.C., Pisani G.B.,
RA   Rogic G., Molinas S.M., Trumper L., Pignataro O.P., Monasterolo L.A.;
RT   "Localization and functional activity of cytochrome P450 side chain
RT   cleavage enzyme (CYP11A1) in the adult rat kidney.";
RL   Mol. Cell. Endocrinol. 332:253-260(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. 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:0000269|PubMed:21075169, ECO:0000269|PubMed:2170421,
CC       ECO:0000269|PubMed:3948785}; Peripheral membrane protein {ECO:0000305}.
CC       Note=Localizes to the matrix side of the mitochondrion inner membrane.
CC       {ECO:0000269|PubMed:3948785}.
CC   -!- TISSUE SPECIFICITY: Expressed in the kidney where it localizes to the
CC       distal convoluted tubule and the thick ascending limb of the loop of
CC       Henle (at protein level) (PubMed:21075169). In the ovary, highly
CC       expressed in interstitial cells (at protein level) (PubMed:3948785).
CC       Also expressed in adrenal gland and testis (PubMed:3123325).
CC       {ECO:0000269|PubMed:21075169, ECO:0000269|PubMed:3123325,
CC       ECO:0000269|PubMed:3948785}.
CC   -!- INDUCTION: Induced by FSH or pregnant mare's serum gonadotropin in
CC       ovaries of estrogen-treated immature rats in vivo.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; J05156; AAA40989.1; -; mRNA.
DR   EMBL; M63133; AAA40958.1; -; Genomic_DNA.
DR   EMBL; M63125; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63126; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63127; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63128; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63129; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63130; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63131; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; M63132; AAA40958.1; JOINED; Genomic_DNA.
DR   EMBL; BC089100; AAH89100.1; -; mRNA.
DR   EMBL; M22615; AAA62267.1; -; mRNA.
DR   PIR; A34164; A34164.
DR   RefSeq; NP_058982.1; NM_017286.3.
DR   AlphaFoldDB; P14137; -.
DR   SMR; P14137; -.
DR   STRING; 10116.ENSRNOP00000010831; -.
DR   BindingDB; P14137; -.
DR   ChEMBL; CHEMBL5246; -.
DR   DrugCentral; P14137; -.
DR   iPTMnet; P14137; -.
DR   PhosphoSitePlus; P14137; -.
DR   PaxDb; 10116-ENSRNOP00000010831; -.
DR   GeneID; 29680; -.
DR   KEGG; rno:29680; -.
DR   UCSC; RGD:69325; rat.
DR   AGR; RGD:69325; -.
DR   CTD; 1583; -.
DR   RGD; 69325; Cyp11a1.
DR   eggNOG; KOG0159; Eukaryota.
DR   HOGENOM; CLU_001570_28_4_1; -.
DR   InParanoid; P14137; -.
DR   OrthoDB; 2658719at2759; -.
DR   PhylomeDB; P14137; -.
DR   BRENDA; 1.14.15.6; 5301.
DR   Reactome; R-RNO-196108; Pregnenolone biosynthesis.
DR   Reactome; R-RNO-211976; Endogenous sterols.
DR   SABIO-RK; P14137; -.
DR   UniPathway; UPA00229; -.
DR   UniPathway; UPA00296; -.
DR   PRO; PR:P14137; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030061; C:mitochondrial crista; IDA:RGD.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; IDA:RGD.
DR   GO; GO:0015485; F:cholesterol binding; IMP:RGD.
DR   GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; IMP:RGD.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD.
DR   GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:RGD.
DR   GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR   GO; GO:0071276; P:cellular response to cadmium ion; IEP:RGD.
DR   GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR   GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
DR   GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR   GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR   GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR   GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR   GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR   GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD.
DR   GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0060014; P:granulosa cell differentiation; IEP:RGD.
DR   GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR   GO; GO:0033327; P:Leydig cell differentiation; IEP:RGD.
DR   GO; GO:0008584; P:male gonad development; IEP:RGD.
DR   GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR   GO; GO:0007617; P:mating behavior; IMP:RGD.
DR   GO; GO:0006082; P:organic acid metabolic process; IEP:RGD.
DR   GO; GO:0018958; P:phenol-containing compound metabolic process; IEP:RGD.
DR   GO; GO:0018963; P:phthalate metabolic process; IEP:RGD.
DR   GO; GO:0043279; P:response to alkaloid; IEP:RGD.
DR   GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR   GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR   GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR   GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR   GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR   GO; GO:0060992; P:response to fungicide; IEP:RGD.
DR   GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
DR   GO; GO:0033595; P:response to genistein; IEP:RGD.
DR   GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR   GO; GO:0042542; P:response to hydrogen peroxide; IMP:RGD.
DR   GO; GO:0017085; P:response to insecticide; IEP:RGD.
DR   GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
DR   GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR   GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR   GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR   GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0014037; P:Schwann cell differentiation; IEP:RGD.
DR   GO; GO:0006694; P:steroid biosynthetic process; IMP:RGD.
DR   GO; GO:0061370; P:testosterone biosynthetic process; IEP:RGD.
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.
DR   Genevisible; P14137; RN.
PE   1: Evidence at protein 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..36
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P00189"
FT   CHAIN           37..526
FT                   /note="Cholesterol side-chain cleavage enzyme,
FT                   mitochondrial"
FT                   /id="PRO_0000003590"
FT   BINDING         459
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   526 AA;  60586 MW;  B2930E40018DC1EE CRC64;
     MLAKGLCLRS VLVKSCQPFL SPVWQGPGLA TGNGAGISST NSPRSFNEIP SPGDNGWINL
     YHFLRENGTH RIHYHHMQNF QKYGPIYREK LGNMESVYIL DPKDAATLFS CEGPNPERYL
     VPPWVAYHQY YQRPIGVLFK SSDAWRKDRI VLNQEVMAPD SIKNFVPLLE GVAQDFIKVL
     HRRIKQQNSG KFSGDISDDL FRFAFESITS VVFGERLGML EEIVDPESQR FIDAVYQMFH
     TSVPMLNMPP DLFRLFRTKT WKDHAAAWDV IFSKADEYTQ NFYWDLRQKR DFSKYPGVLY
     SLLGGNKLPF KNIQANITEM LAGGVDTTSM TLQWNLYEMA HNLKVQEMLR AEVLAARRQA
     QGDMAKMVQL VPLLKASIKE TLRLHPISVT LQRYIVNDLV LRNYKIPAKT LVQVASYAMG
     RESSFFPNPN KFDPTRWLEK SQNTTHFRYL GFGWGVRQCL GRRIAELEMT IFLINVLENF
     RIEVQSIRDV GTKFNLILMP EKPIFFNFQP LKQDLGSTMP RKGDTV
//