TARGETID

T33641

FORMERID

TTDI02047

UNIPROID

CP46A_HUMAN

TARGNAME

Cholesterol 24-hydroxylase (CYP46A1)

GENENAME

CYP46A1

TARGTYPE

Clinical trial target

SYNONYMS

Cytochrome P450 46A1; CYP46; Cholesterol 24S-hydroxylase; Cholesterol 24-monooxygenase; CH24H

FUNCTION

Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation. By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning. Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis. Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain. May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole. P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain.

PDBSTRUC

4J14; 4FIA; 4ENH; 3MDV; 3MDT

BIOCLASS

Paired donor oxygen oxidoreductase

ECNUMBER

EC 1.14.14.25

SEQUENCE

MSPGLLLLGSAVLLAFGLCCTFVHRARSRYEHIPGPPRPSFLLGHLPCFWKKDEVGGRVLQDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKDSKMYRALQTVFGERLFGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLMETFNEKAEQLVEILEAKADGQTPVSMQDMLTYTAMDILAKAAFGMETSMLLGAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQLREVRESIRFLRQVGRDWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFFIAGHETSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQVLKESLRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYFEDPLTFNPDRFGPGAPKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLLQRLEFRLVPGQRFGLQEQATLKPLDPVLCTLRPRGWQPAPPPPPC

DRUGINFO

TAK-935

DRUGINFO

PMID25514969-Compound-10

DRUGINFO

PMID25514969-Compound-11

DRUGINFO

PMID25514969-Compound-12

DRUGINFO

PMID25514969-Compound-13

DRUGINFO

PMID25514969-Compound-8

DRUGINFO

PMID25514969-Compound-9

DRUGINFO

PMID25514969-Compound-Figure2-2