Cholesterol 24-hydroxylase
Details
- Name
- Cholesterol 24-hydroxylase
- Kind
- protein
- Synonyms
- 1.14.14.25
- CH24H
- Cholesterol 24-monooxygenase
- Cholesterol 24S-hydroxylase
- CYP46
- Cytochrome P450 46A1
- Gene Name
- CYP46A1
- UniProtKB Entry
- Q9Y6A2Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0054056|Cholesterol 24-hydroxylase MSPGLLLLGSAVLLAFGLCCTFVHRARSRYEHIPGPPRPSFLLGHLPCFWKKDEVGGRVL QDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKDSKMYRALQTVFGERL FGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLMETFNEKAEQLVEILEAKADGQTPVSM QDMLTYTAMDILAKAAFGMETSMLLGAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQL REVRESIRFLRQVGRDWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFF IAGHETSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQVLKES LRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYFEDPLTFNPDRFGPGA PKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLLQRLEFRLVPGQRFGLQEQATLKPLD PVLCTLRPRGWQPAPPPPPC
- Number of residues
- 500
- Molecular Weight
- 56820.535
- Theoretical pI
- Not Available
- GO Classification
- Not Available
- General Function
- P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation (PubMed:10377398, PubMed:14640697, PubMed:18621681, PubMed:25017465). 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 (By similarity). 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 (PubMed:12077124, PubMed:14640697, PubMed:28190002). 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 (PubMed:25017465). May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole (PubMed:20667828)
- Specific Function
- Cholesterol 24-hydroxylase activity
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- 3-23
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0054057|Cholesterol 24-hydroxylase (CYP46A1) ATGAGCCCCGGGCTGCTGCTGCTCGGCAGCGCCGTCCTGCTCGCCTTCGGCCTCTGCTGC ACCTTCGTGCACCGCGCTCGCAGCCGCTACGAGCACATCCCCGGGCCGCCGCGGCCCAGT TTCCTTCTAGGACACCTCCCCTGCTTTTGGAAAAAGGATGAGGTTGGTGGCCGTGTGCTC CAAGATGTGTTTTTGGATTGGGCTAAGAAGTATGGACCTGTTGTGCGGGTCAACGTCTTC CACAAAACCTCAGTCATCGTCACGAGTCCTGAGTCGGTTAAGAAGTTCCTGATGTCAACC AAGTACAACAAGGACTCCAAGATGTACCGTGCGCTCCAGACTGTGTTTGGTGAGAGACTC TTCGGCCAAGGCTTGGTGTCCGAATGCAACTATGAGCGCTGGCACAAGCAGCGGAGAGTC ATAGACCTGGCCTTCAGCCGGAGCTCCTTGGTTAGCTTAATGGAAACATTCAACGAGAAG GCTGAGCAGCTGGTGGAGATTCTAGAAGCCAAGGCAGATGGGCAGACCCCAGTGTCCATG CAGGACATGCTGACCTACACCGCCATGGACATCCTGGCCAAGGCAGCTTTTGGGATGGAG ACCAGTATGCTGCTGGGTGCCCAGAAGCCTCTGTCCCAGGCAGTGAAACTTATGTTGGAG GGAATCACTGCGTCCCGCAACACTCTGGCAAAGTTCCTGCCAGGGAAGAGGAAGCAGCTC CGGGAGGTCCGGGAGAGCATTCGCTTCCTGCGCCAGGTGGGCAGGGACTGGGTCCAGCGC CGCCGGGAAGCCCTGAAGAGGGGCGAGGAGGTTCCTGCCGACATCCTCACACAGATTCTG AAAGCTGAAGAGGGAGCCCAGGACGACGAGGGTCTGCTGGACAACTTCGTCACCTTCTTC ATTGCTGGTCACGAGACCTCTGCCAACCACTTGGCGTTCACAGTGATGGAGCTGTCTCGC CAGCCAGAGATCGTGGCAAGGCTGCAGGCCGAGGTGGATGAGGTCATTGGTTCTAAGAGG TACCTGGATTTCGAGGACCTGGGGAGACTGCAGTACCTGTCCCAGGTCCTCAAAGAGTCG CTGAGGCTGTACCCACCAGCATGGGGCACCTTTCGCCTGCTGGAAGAGGAGACCTTGATT GATGGGGTCAGAGTCCCCGGCAACACCCCGCTCTTGTTCAGCACCTATGTCATGGGGCGG ATGGACACATACTTTGAGGACCCGCTGACTTTCAACCCCGATCGCTTCGGCCCTGGAGCA CCCAAGCCACGGTTCACCTACTTCCCCTTCTCCCTGGGCCACCGCTCCTGCATCGGGCAG CAGTTTGCTCAGATGGAGGTGAAGGTGGTCATGGCAAAGCTGCTGCAGAGGCTGGAGTTC CGGCTGGTGCCCGGGCAGCGCTTCGGGCTGCAGGAGCAGGCCACACTCAAGCCACTGGAC CCCGTGCTGTGCACCCTGCGGCCCCGCGGCTGGCAGCCCGCACCCCCACCACCCCCCTGC TGA
- Chromosome Location
- 14
- Locus
- 14q32.2
- External Identifiers
Resource Link UniProtKB ID Q9Y6A2 UniProtKB Entry Name CP46A_HUMAN GeneCard ID CYP46A1 HGNC ID HGNC:2641 PDB ID(s) 2Q9F, 2Q9G, 3MDM, 3MDR, 3MDT, 3MDV, 4ENH, 4FIA, 4J14, 7LRL, 7LS3, 7LS4, 7N3L, 7N3M, 7N6F KEGG ID hsa:10858 IUPHAR/Guide To Pharmacology ID 1373 NCBI Gene ID 10858 - General References
- Not Available
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Soticlestat investigational yes target inhibitor Details