ID   Q19P45_RAT              Unreviewed;       182 AA.
AC   Q19P45;
DT   11-JUL-2006, integrated into UniProtKB/TrEMBL.
DT   11-JUL-2006, sequence version 1.
DT   27-MAR-2024, entry version 97.
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|RuleBase:RU364077};
DE   AltName: Full=Cholesterol desmolase {ECO:0000256|RuleBase:RU364077};
DE   Flags: Fragment;
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 {ECO:0000313|EMBL:ABF70958.1};
RN   [1] {ECO:0000313|EMBL:ABF70958.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=W {ECO:0000313|EMBL:ABF70958.1};
RA   Si J.L., Li J., Xu X.Q.;
RL   Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
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=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin]
CC         = 18-hydroxy-11-deoxycorticosterone + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76151, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC         ChEBI:CHEBI:195166; Evidence={ECO:0000256|ARBA:ARBA00035593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76152;
CC         Evidence={ECO:0000256|ARBA:ARBA00035593};
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:RU364077}.
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DR   EMBL; DQ515795; ABF70958.1; -; mRNA.
DR   AlphaFoldDB; Q19P45; -.
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; IPR002399; Cyt_P450_mitochondrial.
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; PR00408; MITP450.
DR   SUPFAM; SSF48264; 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:RU364077};
KW   Iron {ECO:0000256|RuleBase:RU364077};
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:RU364077};
KW   Mitochondrion {ECO:0000256|RuleBase:RU364077};
KW   Monooxygenase {ECO:0000256|RuleBase:RU364077};
KW   Oxidoreductase {ECO:0000256|RuleBase:RU364077};
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   NON_TER         1
FT                   /evidence="ECO:0000313|EMBL:ABF70958.1"
FT   NON_TER         182
FT                   /evidence="ECO:0000313|EMBL:ABF70958.1"
SQ   SEQUENCE   182 AA;  20867 MW;  830425ADBEFCF915 CRC64;
     LCLRSVLVKS CQPFLSPVWQ GPGLATGNGA GISSTNSPRS FNEIPSPGDN GWINLYHFLR
     ENGTHRIHYH HMQNFQKYGP IYREKLGNME SVYILDPKDA ATLFSCEGPN PERYLVPPWV
     AYHQYYQRPI GVLFKSSDAW RKDRIVLNQE VMAPDSIKNF VPLLEGVAQD FIKVLHRRIK
     QQ
//