| IED ID | IndEnz0002006986 |
| Enzyme Type ID | protease006986 |
| Protein Name |
Sterol 26-hydroxylase, mitochondrial EC 1.14.15.15 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase Cytochrome P-450C27/25 Cytochrome P450 27 Sterol 27-hydroxylase Vitamin D 3 25-hydroxylase |
| Gene Name | Cyp27a1 Cyp27 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MAVLSRMRLRWALLDTRVMGHGLCPQGARAKAAIPAALRDHESTEGPGTGQDRPRLRSLAELPGPGTLRFLFQLFLRGYVLHLHELQALNKAKYGPMWTTTFGTRTNVNLASAPLLEQVMRQEGKYPIRDSMEQWKEHRDHKGLSYGIFITQGQQWYHLRHSLNQRMLKPAEAALYTDALNEVISDFIARLDQVRTESASGDQVPDVAHLLYHLALEAICYILFEKRVGCLEPSIPEDTATFIRSVGLMFKNSVYVTFLPKWSRPLLPFWKRYMNNWDNIFSFGEKMIHQKVQEIEAQLQAAGPDGVQVSGYLHFLLTKELLSPQETVGTFPELILAGVDTTSNTLTWALYHLSKNPEIQEALHKEVTGVVPFGKVPQNKDFAHMPLLKAVIKETLRLYPVVPTNSRIITEKETEINGFLFPKNTQFVLCHYVVSRDPSVFPEPESFQPHRWLRKREDDNSGIQHPFGSVPFGYGVRSCLGRRIAELEMQLLLSRLIQKYEVVLSPGMGEVKSVSRIVLVPSKKVSLRFLQRQ |
| Enzyme Length | 533 |
| Uniprot Accession Number | P17178 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=5beta-cholestane-3alpha,7alpha,12alpha-triol + 5 H(+) + 3 O2 + 6 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + 4 H2O + 6 oxidized [adrenodoxin]; Xref=Rhea:RHEA:34631, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16496, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:58734; EC=1.14.15.15; Evidence={ECO:0000250|UniProtKB:P17177, ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34632; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=cholestanol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-26-hydroxycholestanol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:53812, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86570, ChEBI:CHEBI:137688; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53813; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-3beta-hydroxycholest-5-en-7-one-26-al + H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta-hydroxycholest-5-en-7-one-26-oate + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:47380, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:87677, ChEBI:CHEBI:87678; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47381; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-3beta,26-dihydroxycholest-5-en-7-one + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta-hydroxycholest-5-en-7-one-26-al + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:47376, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:87653, ChEBI:CHEBI:87677; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47377; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=7-oxocholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta,26-dihydroxycholest-5-en-7-one + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:47344, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:64294, ChEBI:CHEBI:87653; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47345; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=calciol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = calcidiol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46588, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17933, ChEBI:CHEBI:28940, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:2175615};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46589; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:40231, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:48939, ChEBI:CHEBI:48940; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40232; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=cholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-cholest-5-ene-3beta,26-diol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46400, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:76591; Evidence={ECO:0000269|PubMed:2175615};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46401; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=(25R)-3beta,4beta-dihydroxycholest-5-en-26-al + H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta,4beta-dihydroxycholest-5-en-26-oate + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46436, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86115, ChEBI:CHEBI:86116; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46437; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-4beta,26-dihydroxycholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta,4beta-dihydroxycholest-5-en-26-al + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46432, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86113, ChEBI:CHEBI:86115; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46433; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=4beta-hydroxycholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-4beta,26-dihydroxycholesterol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46428, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:85778, ChEBI:CHEBI:86113; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46429; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-3beta-hydroxy-5-cholesten-26-al + H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta-hydroxy-5-cholestenoate + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:45236, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86096, ChEBI:CHEBI:86098; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45237; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-cholest-5-ene-3beta,26-diol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3beta-hydroxy-5-cholesten-26-al + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46092, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:76591, ChEBI:CHEBI:86096; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46093; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:34627, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:48940, ChEBI:CHEBI:58734; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34628; Evidence={ECO:0000250|UniProtKB:Q02318}; CATALYTIC ACTIVITY: Reaction=5beta-cholestane-3alpha,7alpha,12alpha-triol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:14373, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16496, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:48939; Evidence={ECO:0000250|UniProtKB:Q02318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14374; Evidence={ECO:0000250|UniProtKB:Q02318}; |
| DNA Binding | |
| EC Number | 1.14.15.15 |
| Enzyme Function | FUNCTION: Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid. Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways. May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism. Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis (By similarity). Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (PubMed:2175615). {ECO:0000250|UniProtKB:Q02318, ECO:0000269|PubMed:2175615}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Hormone biosynthesis; cholecalciferol biosynthesis. {ECO:0000250|UniProtKB:Q02318}.; PATHWAY: Steroid metabolism; cholesterol degradation. {ECO:0000250|UniProtKB:Q02318}.; PATHWAY: Lipid metabolism; bile acid biosynthesis. {ECO:0000250|UniProtKB:Q02318}. |
| nucleotide Binding | |
| Features | Chain (1); Erroneous initiation (1); Metal binding (1); Modified residue (4); Region (2); Sequence conflict (9); Transit peptide (1) |
| Keywords | Acetylation;Cholesterol metabolism;Direct protein sequencing;Heme;Iron;Lipid biosynthesis;Lipid metabolism;Membrane;Metal-binding;Mitochondrion;Mitochondrion inner membrane;Monooxygenase;Oxidoreductase;Reference proteome;Steroid biosynthesis;Steroid metabolism;Sterol metabolism;Transit peptide |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein {ECO:0000305|PubMed:19401463}. Note=Post-translationally targeted to mitochondria. All three of the receptor proteins in the TOM complex, TOMM70, TOMM20 and TOMM22 are required for the translocation across the mitochondrial outer membrane. After translocation into the matrix, associates with the inner membrane as a membrane extrinsic protein. {ECO:0000305|PubMed:19401463}. |
| Modified Residue | MOD_RES 142; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q9DBG1; MOD_RES 375; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q9DBG1; MOD_RES 512; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q9DBG1; MOD_RES 523; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q9DBG1 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12909643; 17118558; 19665519; 24280213; 29360226; |
| Motif | |
| Gene Encoded By | |
| Mass | 60,733 |
| Kinetics | |
| Metal Binding | METAL 479; /note=Iron (heme axial ligand) |
| Rhea ID | RHEA:34631; RHEA:34632; RHEA:53812; RHEA:53813; RHEA:47380; RHEA:47381; RHEA:47376; RHEA:47377; RHEA:47344; RHEA:47345; RHEA:46588; RHEA:46589; RHEA:40231; RHEA:40232; RHEA:46400; RHEA:46401; RHEA:46436; RHEA:46437; RHEA:46432; RHEA:46433; RHEA:46428; RHEA:46429; RHEA:45236; RHEA:45237; RHEA:46092; RHEA:46093; RHEA:34627; RHEA:34628; RHEA:14373; RHEA:14374 |
| Cross Reference Brenda | 1.14.15.15; |