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Identification
HMDB Protein ID HMDBP12699
Secondary Accession Numbers None
Name 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Synonyms
  1. 24-OHase
  2. Vitamin D(3) 24-hydroxylase
  3. Cytochrome P450 24A1
  4. Cytochrome P450-CC24
Gene Name CYP24A1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24-oxidation pathway, 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:2026586, PubMed:16617161, PubMed:10231362). 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:10231362, PubMed:16617161). Hydroxylates at C-24 or 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:2026586).
Pathways
  • MicroRNAs in cancer
  • Parathyroid hormone synthesis, secretion and action
  • Steroid biosynthesis
Reactions Not Available
GO Classification
Biological Process
fatty acid omega-oxidation
vitamin D metabolic process
osteoblast differentiation
vitamin D catabolic process
response to vitamin D
Cellular Component
mitochondrion
nucleoplasm
Molecular Function
vitamin D 24-hydroxylase activity
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
25-hydroxycholecalciferol-23-hydroxylase activity
vitamin D 25-hydroxylase activity
iron ion binding
1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity
25-hydroxycholecalciferol-24-hydroxylase activity
heme binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 514
Molecular Weight 59447.565
Theoretical pI 9.103
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q09128
UniProtKB/Swiss-Prot Entry Name CP24A_RAT
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. 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. [PubMed:15574355 ]
  3. Ohyama Y, Noshiro M, Okuda K: Cloning and expression of cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase. FEBS Lett. 1991 Jan 28;278(2):195-8. doi: 10.1016/0014-5793(91)80115-j. [PubMed:1991512 ]
  4. Ohyama Y, Noshiro M, Eggertsen G, Gotoh O, Kato Y, Bjorkhem I, Okuda K: Structural characterization of the gene encoding rat 25-hydroxyvitamin D3 24-hydroxylase. Biochemistry. 1993 Jan 12;32(1):76-82. doi: 10.1021/bi00052a011. [PubMed:8418863 ]
  5. Hahn CN, Kerry DM, Omdahl JL, May BK: Identification of a vitamin D responsive element in the promoter of the rat cytochrome P450(24) gene. Nucleic Acids Res. 1994 Jun 25;22(12):2410-6. doi: 10.1093/nar/22.12.2410. [PubMed:8036172 ]
  6. Ohyama Y, Okuda K: Isolation and characterization of a cytochrome P-450 from rat kidney mitochondria that catalyzes the 24-hydroxylation of 25-hydroxyvitamin D3. J Biol Chem. 1991 May 15;266(14):8690-5. [PubMed:2026586 ]
  7. Sakaki T, Sawada N, Nonaka Y, Ohyama Y, Inouye K: Metabolic studies using recombinant escherichia coli cells producing rat mitochondrial CYP24 CYP24 can convert 1alpha,25-dihydroxyvitamin D3 to calcitroic acid. Eur J Biochem. 1999 May;262(1):43-8. doi: 10.1046/j.1432-1327.1999.00375.x. [PubMed:10231362 ]
  8. Tieu EW, Li W, Chen J, Kim TK, Ma D, Slominski AT, Tuckey RC: Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1. J Steroid Biochem Mol Biol. 2015 May;149:153-65. doi: 10.1016/j.jsbmb.2015.02.010. Epub 2015 Feb 26. [PubMed:25727742 ]
  9. Annalora AJ, Goodin DB, Hong WX, Zhang Q, Johnson EF, Stout CD: Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in vitamin D metabolism. J Mol Biol. 2010 Feb 19;396(2):441-51. doi: 10.1016/j.jmb.2009.11.057. Epub 2009 Dec 1. [PubMed:19961857 ]