ID   Q6NV84_MOUSE            Unreviewed;       526 AA.
AC   Q6NV84;
DT   05-JUL-2004, integrated into UniProtKB/TrEMBL.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 114.
DE   RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000256|ARBA:ARBA00019844, ECO:0000256|RuleBase:RU364077};
DE            EC=1.14.15.6 {ECO:0000256|ARBA:ARBA00012764, ECO:0000256|RuleBase:RU364077};
DE   AltName: Full=Cholesterol desmolase {ECO:0000256|RuleBase:RU364077};
GN   Name=Cyp11a1 {ECO:0000313|EMBL:AAH68264.1, ECO:0000313|MGI:MGI:88582};
GN   Synonyms=Cypxia1 {ECO:0000313|EMBL:AAH68264.1}, P450scc
GN   {ECO:0000313|EMBL:AAH68264.1}, Scc {ECO:0000313|EMBL:AAH68264.1};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090 {ECO:0000313|EMBL:AAH68264.1};
RN   [1] {ECO:0000313|EMBL:AAH68264.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J {ECO:0000313|EMBL:AAH68264.1};
RC   TISSUE=Embryo {ECO:0000313|EMBL:AAH68264.1};
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RA   Gerhard D.S., Wagner L., Feingold E.A., Shenmen C.M., Grouse L.H.,
RA   Schuler G., Klein S.L., Old S., Rasooly R., Good P., Guyer M., Peck A.M.,
RA   Derge J.G., Lipman D., Collins F.S., Jang W., Sherry S., Feolo M.,
RA   Misquitta L., Lee E., Rotmistrovsky K., Greenhut S.F., Schaefer C.F.,
RA   Buetow K., Bonner T.I., Haussler D., Kent J., Kiekhaus M., Furey T.,
RA   Brent M., Prange C., Schreiber K., Shapiro N., Bhat N.K., Hopkins R.F.,
RA   Hsie F., Driscoll T., Soares M.B., Casavant T.L., Scheetz T.E.,
RA   Brown-stein M.J., Usdin T.B., Toshiyuki S., Carninci P., Piao Y.,
RA   Dudekula D.B., Ko M.S., Kawakami K., Suzuki Y., Sugano S., Gruber C.E.,
RA   Smith M.R., Simmons B., Moore T., Waterman R., Johnson S.L., Ruan Y.,
RA   Wei C.L., Mathavan S., Gunaratne P.H., Wu J., Garcia A.M., Hulyk S.W.,
RA   Fuh E., Yuan Y., Sneed A., Kowis C., Hodgson A., Muzny D.M., McPherson J.,
RA   Gibbs R.A., Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S.,
RA   Sanchez A., Whiting M., Madari A., Young A.C., Wetherby K.D., Granite S.J.,
RA   Kwong P.N., Brinkley C.P., Pearson R.L., Bouffard G.G., Blakesly R.W.,
RA   Green E.D., Dickson M.C., Rodriguez A.C., Grimwood J., Schmutz J.,
RA   Myers R.M., Butterfield Y.S., Griffith M., Griffith O.L., Krzywinski M.I.,
RA   Liao N., Morin R., Morrin R., Palmquist D., Petrescu A.S., Skalska U.,
RA   Smailus D.E., Stott J.M., Schnerch A., Schein J.E., Jones S.J., Holt R.A.,
RA   Baross A., Marra M.A., Clifton S., Makowski K.A., Bosak S., Malek J.;
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).
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:0000256|RuleBase:RU364077}.
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:0000256|ARBA:ARBA00000397};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344;
CC         Evidence={ECO:0000256|ARBA:ARBA00000397};
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:0000256|ARBA:ARBA00034008};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340;
CC         Evidence={ECO:0000256|ARBA:ARBA00034008};
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:0000256|ARBA:ARBA00034072};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336;
CC         Evidence={ECO:0000256|ARBA:ARBA00034072};
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:0000256|ARBA:ARBA00000117};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740;
CC         Evidence={ECO:0000256|ARBA:ARBA00000117};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000256|ARBA:ARBA00001971,
CC         ECO:0000256|RuleBase:RU364077};
CC   -!- PATHWAY: Lipid metabolism; C21-steroid hormone metabolism.
CC       {ECO:0000256|ARBA:ARBA00005108, ECO:0000256|RuleBase:RU364077}.
CC   -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC       {ECO:0000256|ARBA:ARBA00004731}.
CC   -!- SUBUNIT: Interacts with FDX1/adrenodoxin.
CC       {ECO:0000256|ARBA:ARBA00011573}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000256|RuleBase:RU364077}; Peripheral membrane protein
CC       {ECO:0000256|RuleBase:RU364077}. Note=Localizes to the matrix side of
CC       the mitochondrion inner membrane. {ECO:0000256|RuleBase:RU364077}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC       {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}.
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DR   EMBL; BC068264; AAH68264.1; -; mRNA.
DR   AlphaFoldDB; Q6NV84; -.
DR   EPD; Q6NV84; -.
DR   AGR; MGI:88582; -.
DR   MGI; MGI:88582; Cyp11a1.
DR   UniPathway; UPA00229; -.
DR   UniPathway; UPA00296; -.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0008207; P:C21-steroid hormone metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
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 {ECO:0000256|RuleBase:RU364077};
KW   Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|RuleBase:RU000461};
KW   Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|RuleBase:RU000461};
KW   Lipid metabolism {ECO:0000256|RuleBase:RU364077};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU364077};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|RuleBase:RU000461};
KW   Mitochondrion {ECO:0000256|RuleBase:RU364077};
KW   Monooxygenase {ECO:0000256|ARBA:ARBA00023033,
KW   ECO:0000256|RuleBase:RU000461};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW   ECO:0000256|RuleBase:RU000461};
KW   Steroid metabolism {ECO:0000256|RuleBase:RU364077};
KW   Steroidogenesis {ECO:0000256|RuleBase:RU364077};
KW   Sterol metabolism {ECO:0000256|RuleBase:RU364077};
KW   Transit peptide {ECO:0000256|ARBA:ARBA00022946,
KW   ECO:0000256|RuleBase:RU364077}.
FT   REGION          30..49
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        30..48
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   526 AA;  60305 MW;  E5006A16F3512B42 CRC64;
     MLAKGLSLRS VLVKGCQPFL SPTWQGPVLS TGKGAGTSTS SPRSFNEIPS PGDNGWLNLY
     HFWRESGTQK IHYHQMQSFQ KYGPIYREKL GTLESVYIVD PKDASILFSC EGPNPERFLV
     PPWVAYHQYY QRPIGVLFKS SDAWKKDRIV LNQEVMAPGA IKNFVPLLEG VAQDFIKVLH
     RRIKQQNSGN FSGVISDDLF RFSFESISSV IFGERMGMLE EIVDPEAQRF INAVYQMFHT
     SVPMLNLPPD FFRLLRTKTW KDHAAAWDVI FNKADEYTQN FYWDLRQKRD FSQYPGVLYS
     LLGGNKLPFK NIQANITEML AGGVDTTSMT LQWNLYEMAH NLKVQEMLRA EVLAARRQAQ
     GDMAKMVQLV SLLKASIKET LRLHPISVTL QRYTVNDLVL RNYKIPAKTL VQVASFAMGR
     DPGFFPNPNK FDPTRWLEKS QNTTHFRYLG FGWGVRQCLG RRIAELEMTI LLINLLENFR
     IEVQNLRDVG TKFSLILMPE NPILFNFQPL KQDLGPAVTR KDNTVN
//