| IED ID | IndEnz0010001300 |
| Enzyme Type ID | esterase001300 |
| Protein Name |
Cytochrome P450 7A1 24-hydroxycholesterol 7-alpha-hydroxylase EC 1.14.14.26 CYPVII Cholesterol 7-alpha-hydroxylase Cholesterol 7-alpha-monooxygenase EC 1.14.14.23 |
| Gene Name | CYP7A1 CYP7 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MMTTSLIWGIAIAACCCLWLILGIRRRQTGEPPLENGLIPYLGCALQFGANPLEFLRANQRKHGHVFTCKLMGKYVHFITNPLSYHKVLCHGKYFDWKKFHFATSAKAFGHRSIDPMDGNTTENINDTFIKTLQGHALNSLTESMMENLQRIMRPPVSSNSKTAAWVTEGMYSFCYRVMFEAGYLTIFGRDLTRRDTQKAHILNNLDNFKQFDKVFPALVAGLPIHMFRTAHNAREKLAESLRHENLQKRESISELISLRMFLNDTLSTFDDLEKAKTHLVVLWASQANTIPATFWSLFQMIRNPEAMKAATEEVKRTLENAGQKVSLEGNPICLSQAELNDLPVLDSIIKESLRLSSASLNIRTAKEDFTLHLEDGSYNIRKDDIIALYPQLMHLDPEIYPDPLTFKYDRYLDENGKTKTTFYCNGLKLKYYYMPFGSGATICPGRLFAIHEIKQFLILMLSYFELELIEGQAKCPPLDQSRAGLGILPPLNDIEFKYKFKHL |
| Enzyme Length | 504 |
| Uniprot Accession Number | P22680 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase] = 7alpha-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:21812, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:17500, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.23; Evidence={ECO:0000269|PubMed:11013305, ECO:0000269|PubMed:12077124, ECO:0000269|PubMed:2384150};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21813; Evidence={ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124, ECO:0000305|PubMed:2384150}; CATALYTIC ACTIVITY: Reaction=4beta-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein reductase] = 4beta,7alpha-dihydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46120, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:85778, ChEBI:CHEBI:85779; Evidence={ECO:0000269|PubMed:12077124};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46121; Evidence={ECO:0000305|PubMed:12077124}; CATALYTIC ACTIVITY: Reaction=5alpha-cholest-7-en-3beta-ol + O2 + reduced [NADPH--hemoprotein reductase] = 7alpha,8alpha-epoxy-5alpha-cholestan-3beta-ol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53256, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17168, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137063; Evidence={ECO:0000269|PubMed:21813643};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53257; Evidence={ECO:0000305|PubMed:21813643}; CATALYTIC ACTIVITY: Reaction=5alpha-cholest-7-en-3beta-ol + O2 + reduced [NADPH--hemoprotein reductase] = 5alpha-cholestan-7-oxo-3beta-ol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53252, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17168, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137062; Evidence={ECO:0000269|PubMed:21813643};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53253; Evidence={ECO:0000305|PubMed:21813643}; CATALYTIC ACTIVITY: Reaction=7-dehydrocholesterol + O2 + reduced [NADPH--hemoprotein reductase] = 7-oxocholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53248, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17759, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:64294; Evidence={ECO:0000269|PubMed:21813643};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53249; Evidence={ECO:0000305|PubMed:21813643}; CATALYTIC ACTIVITY: Reaction=(24S)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein reductase] = (24S)-7alpha-dihydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46124, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:34310, ChEBI:CHEBI:37640, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.26; Evidence={ECO:0000269|PubMed:11013305};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46125; Evidence={ECO:0000305|PubMed:11013305}; CATALYTIC ACTIVITY: Reaction=(24R)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein reductase] = (24R)-7alpha-dihydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:16093, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:50516, ChEBI:CHEBI:50518, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:11013305};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16094; Evidence={ECO:0000305|PubMed:11013305}; |
| DNA Binding | |
| EC Number | 1.14.14.26; 1.14.14.23 |
| Enzyme Function | FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) (PubMed:11013305, PubMed:12077124, PubMed:19965590, PubMed:2384150, PubMed:21813643). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:2384150, PubMed:11013305, PubMed:12077124, PubMed:19965590, PubMed:21813643). Functions as a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis. Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis (PubMed:12077124, PubMed:19965590, PubMed:2384150). 7-alpha hydroxylates several oxysterols, including 4beta-hydroxycholesterol and 24-hydroxycholesterol (PubMed:11013305, PubMed:12077124). Catalyzes the oxidation of the 7,8 double bond of 7-dehydrocholesterol and lathosterol with direct and predominant formation of the 7-keto derivatives (PubMed:21813643). {ECO:0000269|PubMed:11013305, ECO:0000269|PubMed:12077124, ECO:0000269|PubMed:19965590, ECO:0000269|PubMed:21813643, ECO:0000269|PubMed:2384150}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; bile acid biosynthesis. {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124, ECO:0000305|PubMed:2384150}.; PATHWAY: Steroid metabolism; cholesterol degradation. {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124, ECO:0000305|PubMed:2384150}. |
| nucleotide Binding | |
| Features | Beta strand (17); Chain (1); Helix (24); Metal binding (1); Natural variant (4); Sequence conflict (1); Transmembrane (1); Turn (4) |
| Keywords | 3D-structure;Cholesterol metabolism;Endoplasmic reticulum;Heme;Iron;Lipid metabolism;Membrane;Metal-binding;Microsome;Monooxygenase;Oxidoreductase;Reference proteome;Steroid metabolism;Sterol metabolism;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Up-regulated by glucose and by cholestyramine. Down-regulated by chenodeoxycholic acid. {ECO:0000269|PubMed:15796896, ECO:0000269|PubMed:19965590}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:2384150}; Single-pass membrane protein {ECO:0000305}. Microsome membrane {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:2384150}; Single-pass membrane protein {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 3DAX; 3SN5; 3V8D; |
| Mapped Pubmed ID | 10588945; 10777541; 11257258; 11907135; 12011083; 12093884; 12093894; 12116231; 12202481; 12213890; 12554795; 12810154; 12815072; 12865425; 14515446; 14522988; 14592954; 14762172; 15133863; 15205472; 15241483; 15262185; 15333704; 15640003; 15707388; 15736936; 15752749; 15805302; 15910869; 16115473; 16630139; 16709249; 16763159; 16917677; 16937432; 17680536; 17920062; 18078817; 18178499; 18270374; 18307386; 18385139; 18660489; 18665040; 18728123; 18728290; 18996102; 19018779; 19185005; 19343046; 19448895; 19463968; 19537927; 19558216; 19598235; 19850125; 19956635; 20005541; 20031551; 20235787; 20351063; 20403997; 20578904; 20602615; 20686565; 20717043; 20857261; 20872969; 20884100; 21039385; 21147774; 21346769; 21902813; 22058145; 22235657; 22607622; 22713451; 23038264; 23458092; 23626788; 23740208; 24365583; 24582860; 24927729; 25103562; 25360185; 25499945; 25944972; 26333513; 26345803; 26521940; 26936139; 27052530; 27106353; 27155186; 27534992; 29115200; 29171472; 29237721; 29529257; 29721023; 30122083; 30354296; 31578885; 34546511; |
| Motif | |
| Gene Encoded By | |
| Mass | 57,661 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3 uM for cholesterol {ECO:0000269|PubMed:11013305}; KM=6 uM for 24-hydroxycholesterol {ECO:0000269|PubMed:11013305}; KM=1.8 uM for 5alpha-cholest-7-en-3beta-ol (lathosterol) {ECO:0000269|PubMed:21813643}; KM=1.1 uM for cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol) {ECO:0000269|PubMed:21813643}; Vmax=0.184 nmol/min/nmol enzyme toward cholesterol {ECO:0000269|PubMed:12077124}; Vmax=0.087 nmol/min/nmol enzyme toward 4beta-hydroxycholesterol {ECO:0000269|PubMed:12077124}; Note=kcat is 3.7 min(-1) with 5alpha-cholest-7-en-3beta-ol (lathosterol) as substrate. kcat is 2.2 min(-1) with cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol) as substrate. {ECO:0000269|PubMed:21813643}; |
| Metal Binding | METAL 444; /note=Iron (heme axial ligand); /evidence=ECO:0007744|PDB:3DAX |
| Rhea ID | RHEA:21812; RHEA:21813; RHEA:46120; RHEA:46121; RHEA:53256; RHEA:53257; RHEA:53252; RHEA:53253; RHEA:53248; RHEA:53249; RHEA:46124; RHEA:46125; RHEA:16093; RHEA:16094 |
| Cross Reference Brenda | 1.14.14.23; |