1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Details
- Name
- 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
- Kind
- protein
- Synonyms
- 1.14.15.16
- 24-OHase
- CYP24
- Cytochrome P450 24A1
- Cytochrome P450-CC24
- Vitamin D(3) 24-hydroxylase
- Gene Name
- CYP24A1
- UniProtKB Entry
- Q07973Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0004416|1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial MSSPISKSRSLAAFLQQLRSPRQPPRLVTSTAYTSPQPREVPVCPLTAGGETQNAAALPG PTSWPLLGSLLQILWKGGLKKQHDTLVEYHKKYGKIFRMKLGSFESVHLGSPCLLEALYR TESAYPQRLEIKPWKAYRDYRKEGYGLLILEGEDWQRVRSAFQKKLMKPGEVMKLDNKIN EVLADFMGRIDELCDERGHVEDLYSELNKWSFESICLVLYEKRFGLLQKNAGDEAVNFIM AIKTMMSTFGRMMVTPVELHKSLNTKVWQDHTLAWDTIFKSVKACIDNRLEKYSQQPSAD FLCDIYHQNRLSKKELYAAVTELQLAAVETTANSLMWILYNLSRNPQVQQKLLKEIQSVL PENQVPRAEDLRNMPYLKACLKESMRLTPSVPFTTRTLDKATVLGEYALPKGTVLMLNTQ VLGSSEDNFEDSSQFRPERWLQEKEKINPFAHLPFGVGKRMCIGRRLAELQLHLALCWIV RKYDIQATDNEPVEMLHSGTLVPSRELPIAFCQR
- Number of residues
- 514
- Molecular Weight
- 58874.695
- Theoretical pI
- 8.99
- GO Classification
- Functions1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity / 25-hydroxycholecalciferol-23-hydroxylase activity / vitamin D 25-hydroxylase activity
- General Function
- A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:11012668, PubMed:15574355, PubMed:16617161, PubMed:24893882, PubMed:29461981, PubMed:8679605). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:15574355, PubMed:24893882). With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668, PubMed:8679605). Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742). 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 FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:8679605)
- Specific Function
- 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion
- Gene sequence
>lcl|BSEQ0016728|1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) ATGAGCTCCCCCATCAGCAAGAGCCGCTCGCTTGCCGCCTTCCTGCAGCAGCTGCGCAGT CCGAGGCAGCCCCCGAGACTGGTGACATCTACGGCGTACACGTCCCCTCAGCCGCGAGAG GTGCCAGTCTGCCCGCTGACAGCTGGTGGCGAGACTCAGAACGCGGCCGCCCTGCCGGGC CCCACCAGCTGGCCACTGCTGGGCAGCCTGCTGCAGATTCTCTGGAAAGGGGGTCTCAAG AAACAGCACGACACCCTGGTGGAGTACCACAAGAAGTATGGCAAGATTTTCCGCATGAAG TTGGGTTCCTTTGAGTCGGTGCACCTGGGCTCGCCATGCCTGCTGGAAGCGCTGTACCGC ACCGAGAGCGCGTACCCGCAGCGGCTGGAGATCAAACCGTGGAAGGCCTATCGCGACTAC CGCAAAGAAGGCTACGGGCTGCTGATCCTGGAAGGGGAAGACTGGCAGCGGGTCCGGAGT GCCTTTCAAAAGAAACTAATGAAACCAGGGGAAGTGATGAAGCTGGACAACAAAATCAAT GAGGTCTTGGCCGATTTTATGGGCAGAATAGATGAGCTCTGTGATGAAAGAGGCCACGTT GAAGACTTGTACAGCGAACTGAACAAATGGTCGTTTGAAAGTATCTGCCTCGTGTTGTAT GAGAAGAGATTTGGGCTTCTCCAGAAGAATGCAGGGGATGAAGCTGTGAACTTCATCATG GCCATCAAAACAATGATGAGCACGTTTGGGAGGATGATGGTCACTCCAGTCGAGCTGCAC AAGAGCCTCAACACCAAGGTCTGGCAGGACCACACTCTGGCCTGGGACACCATTTTCAAA TCAGTCAAAGCTTGTATCGACAACCGGTTAGAGAAGTATTCTCAGCAGCCTAGTGCAGAT TTCCTTTGTGACATTTATCACCAGAATCGGCTTTCAAAGAAAGAATTGTATGCTGCTGTC ACAGAGCTCCAGCTGGCTGCGGTGGAAACGACAGCAAACAGTCTAATGTGGATTCTCTAC AATTTATCCCGTAATCCCCAAGTGCAACAAAAGCTTCTTAAGGAAATTCAAAGTGTATTA CCTGAGAATCAGGTGCCACGGGCAGAAGATTTGAGGAATATGCCGTATTTAAAAGCCTGT CTGAAAGAATCTATGAGGCTTACGCCGAGTGTACCATTTACAACTCGGACTCTTGACAAG GCAACAGTTCTGGGTGAATATGCTTTACCCAAAGGAACAGTGCTCATGCTAAATACCCAG GTGTTGGGATCCAGTGAAGACAATTTTGAAGATTCAAGTCAGTTTAGACCTGAACGTTGG CTTCAGGAGAAGGAAAAAATTAATCCTTTTGCGCATCTTCCATTTGGCGTTGGAAAAAGA ATGTGCATTGGTCGCCGATTAGCAGAGCTTCAACTGCATTTGGCTCTTTGTTGGATTGTC CGCAAATACGACATCCAGGCCACAGACAATGAGCCTGTTGAGATGCTACACTCAGGCACC CTGGTGCCCAGCCGGGAACTCCCCATCGCGTTTTGCCAGCGATAA
- Chromosome Location
- 20
- Locus
- 20q13.2
- External Identifiers
Resource Link UniProtKB ID Q07973 UniProtKB Entry Name CP24A_HUMAN GenBank Protein ID 306704 GenBank Gene ID L13286 GeneCard ID CYP24A1 GenAtlas ID CYP24A1 HGNC ID HGNC:2602 KEGG ID hsa:1591 IUPHAR/Guide To Pharmacology ID 1365 NCBI Gene ID 1591 - General References
- Chen KS, Prahl JM, DeLuca HF: Isolation and expression of human 1,25-dihydroxyvitamin D3 24-hydroxylase cDNA. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4543-7. [Article]
- Ren S, Nguyen L, Wu S, Encinas C, Adams JS, Hewison M: Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis. J Biol Chem. 2005 May 27;280(21):20604-11. Epub 2005 Mar 23. [Article]
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- Chen KS, DeLuca HF: Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements. Biochim Biophys Acta. 1995 Jul 25;1263(1):1-9. [Article]
- Labuda M, Lemieux N, Tihy F, Prinster C, Glorieux FH: Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps to a different chromosomal location than that of pseudovitamin D-deficient rickets. J Bone Miner Res. 1993 Nov;8(11):1397-406. [Article]
- Sakaki T, Kagawa N, Yamamoto K, Inouye K: Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. Print 2005 Jan 1. [Article]
- Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Broking E, Fehrenbach H, Wingen AM, Guran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M: Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011 Aug 4;365(5):410-21. doi: 10.1056/NEJMoa1103864. Epub 2011 Jun 15. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details CTA018 investigational unknown target Details Calcitriol approved, nutraceutical unknown enzyme substrateinducer Details Ergocalciferol approved, nutraceutical no enzyme substrate Details Paricalcitol approved, investigational unknown enzyme substrate Details Calcifediol approved, nutraceutical unknown enzyme substrate Details Calcipotriol approved unknown enzyme substrate Details Corticotropin approved, investigational, vet_approved unknown enzyme inducer Details