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
Functions
1-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
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
ResourceLink
UniProtKB IDQ07973
UniProtKB Entry NameCP24A_HUMAN
GenBank Protein ID306704
GenBank Gene IDL13286
GeneCard IDCYP24A1
GenAtlas IDCYP24A1
HGNC IDHGNC:2602
KEGG IDhsa:1591
IUPHAR/Guide To Pharmacology ID1365
NCBI Gene ID1591
General References
  1. 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]
  2. 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]
  3. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
  4. 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. [Article]
  5. 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]
  6. 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]
  7. 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]
  8. 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
DrugDrug groupPharmacological action?TypeActionsDetails
CTA018investigationalunknowntargetDetails
Calcitriolapproved, nutraceuticalunknownenzymesubstrateinducerDetails
Ergocalciferolapproved, nutraceuticalnoenzymesubstrateDetails
Paricalcitolapproved, investigationalunknownenzymesubstrateDetails
Calcifediolapproved, nutraceuticalunknownenzymesubstrateDetails
CalcipotriolapprovedunknownenzymesubstrateDetails
Corticotropinapproved, investigational, vet_approvedunknownenzymeinducerDetails