CP24A_HUMAN
ID CP24A_HUMAN Reviewed; 514 AA.
AC Q07973; Q15807; Q32ML3; Q5I2W7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial {ECO:0000303|PubMed:8506296};
DE Short=24-OHase;
DE Short=Vitamin D(3) 24-hydroxylase;
DE EC=1.14.15.16 {ECO:0000269|PubMed:15574355, ECO:0000269|PubMed:16617161, ECO:0000269|PubMed:21675912, ECO:0000269|PubMed:24893882, ECO:0000269|PubMed:8679605};
DE AltName: Full=Cytochrome P450 24A1;
DE AltName: Full=Cytochrome P450-CC24;
DE Flags: Precursor;
GN Name=CYP24A1 {ECO:0000312|HGNC:HGNC:2602}; Synonyms=CYP24;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8506296; DOI=10.1073/pnas.90.10.4543;
RA Chen K.-S., Prahl J.M., Deluca H.F.;
RT "Isolation and expression of human 1,25-dihydroxyvitamin D3 24-hydroxylase
RT cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:4543-4547(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=15788398; DOI=10.1074/jbc.m414522200;
RA Ren S., Nguyen L., Wu S., Encinas C., Adams J.S., Hewison M.;
RT "Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for
RT the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis.";
RL J. Biol. Chem. 280:20604-20611(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104.
RX PubMed=7632726; DOI=10.1016/0167-4781(95)00060-t;
RA Chen K.-S., DeLuca H.F.;
RT "Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene
RT promoter and identification of two vitamin D-responsive elements.";
RL Biochim. Biophys. Acta 1263:1-9(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 258-514 (ISOFORM 1).
RX PubMed=8266831; DOI=10.1002/jbmr.5650081114;
RA Labuda M., Lemieux N., Tihy F., Prinster C., Glorieux F.H.;
RT "Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps to a
RT different chromosomal location than that of pseudovitamin D-deficient
RT rickets.";
RL J. Bone Miner. Res. 8:1397-1406(1993).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8679605; DOI=10.1021/bi960658i;
RA Beckman M.J., Tadikonda P., Werner E., Prahl J., Yamada S., DeLuca H.F.;
RT "Human 25-hydroxyvitamin D3-24-hydroxylase, a multicatalytic enzyme.";
RL Biochemistry 35:8465-8472(1996).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11012668; DOI=10.1046/j.1432-1327.2000.01680.x;
RA Sakaki T., Sawada N., Komai K., Shiozawa S., Yamada S., Yamamoto K.,
RA Ohyama Y., Inouye K.;
RT "Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24.";
RL Eur. J. Biochem. 267:6158-6165(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=15574355; DOI=10.2741/1514;
RA Sakaki T., Kagawa N., Yamamoto K., Inouye K.;
RT "Metabolism of vitamin D3 by cytochromes P450.";
RL Front. Biosci. 10:119-134(2005).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16617161; DOI=10.1124/mol.106.023275;
RA Hamamoto H., Kusudo T., Urushino N., Masuno H., Yamamoto K., Yamada S.,
RA Kamakura M., Ohta M., Inouye K., Sakaki T.;
RT "Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-
RT directed mutagenesis: amino acid residues responsible for species-based
RT difference of CYP24A1 between humans and rats.";
RL Mol. Pharmacol. 70:120-128(2006).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24893882; DOI=10.1111/febs.12862;
RA Tieu E.W., Tang E.K., Tuckey R.C.;
RT "Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-
RT oxidation pathway.";
RL FEBS J. 281:3280-3296(2014).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25727742; DOI=10.1016/j.jsbmb.2015.02.010;
RA Tieu E.W., Li W., Chen J., Kim T.K., Ma D., Slominski A.T., Tuckey R.C.;
RT "Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat
RT and human CYP24A1.";
RL J. Steroid Biochem. Mol. Biol. 149:153-165(2015).
RN [13]
RP FUNCTION.
RX PubMed=29461981; DOI=10.1172/jci98680;
RA Roizen J.D., Li D., O'Lear L., Javaid M.K., Shaw N.J., Ebeling P.R.,
RA Nguyen H.H., Rodda C.P., Thummel K.E., Thacher T.D., Hakonarson H.,
RA Levine M.A.;
RT "CYP3A4 mutation causes vitamin D-dependent rickets type 3.";
RL J. Clin. Invest. 128:1913-1918(2018).
RN [14]
RP VARIANTS HCINF1 GLU-143 DEL; GLN-159; LYS-322; TRP-396 AND SER-409,
RP CHARACTERIZATION OF VARIANTS HCINF1 GLU-143 DEL; GLN-159; LYS-322; TRP-396
RP AND SER-409, AND CATALYTIC ACTIVITY.
RX PubMed=21675912; DOI=10.1056/nejmoa1103864;
RA Schlingmann K.P., Kaufmann M., Weber S., Irwin A., Goos C., John U.,
RA Misselwitz J., Klaus G., Kuwertz-Broking E., Fehrenbach H., Wingen A.M.,
RA Guran T., Hoenderop J.G., Bindels R.J., Prosser D.E., Jones G., Konrad M.;
RT "Mutations in CYP24A1 and idiopathic infantile hypercalcemia.";
RL N. Engl. J. Med. 365:410-421(2011).
CC -!- FUNCTION: A cytochrome P450 monooxygenase with a key role in vitamin D
CC catabolism and calcium homeostasis. Via C24- and C23-oxidation
CC pathways, catalyzes the inactivation of both the vitamin D precursor
CC calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol
CC (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:24893882, PubMed:15574355,
CC PubMed:8679605, PubMed:11012668, PubMed:16617161, PubMed:29461981).
CC With initial hydroxylation at C-24 (via C24-oxidation pathway),
CC performs a sequential 6-step oxidation of calcitriol leading to the
CC formation of the biliary metabolite calcitroic acid (PubMed:24893882,
CC PubMed:15574355). With initial hydroxylation at C-23 (via C23-oxidation
CC pathway), catalyzes sequential oxidation of calcidiol leading to the
CC formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668,
CC PubMed:8679605). Preferentially hydroxylates at C-25 other vitamin D
CC active metabolites, such as CYP11A1-derived secosteroids 20S-
CC hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol
CC (PubMed:25727742). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via FDXR/adrenodoxin
CC reductase and FDX1/adrenodoxin (PubMed:8679605).
CC {ECO:0000269|PubMed:11012668, ECO:0000269|PubMed:15574355,
CC ECO:0000269|PubMed:16617161, ECO:0000269|PubMed:24893882,
CC ECO:0000269|PubMed:25727742, ECO:0000269|PubMed:29461981,
CC ECO:0000269|PubMed:8679605}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcitriol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC calcitetrol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:24964,
CC Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17823,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47799;
CC EC=1.14.15.16; Evidence={ECO:0000269|PubMed:15574355,
CC ECO:0000269|PubMed:16617161, ECO:0000269|PubMed:21675912,
CC ECO:0000269|PubMed:24893882, ECO:0000269|PubMed:8679605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24965;
CC Evidence={ECO:0000305|PubMed:21675912};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcitetrol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (1S)-
CC 1,25-dihydroxy-24-oxocalciol + 2 H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:24972, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47799,
CC ChEBI:CHEBI:47812; EC=1.14.15.16;
CC Evidence={ECO:0000269|PubMed:16617161, ECO:0000269|PubMed:21675912,
CC ECO:0000269|PubMed:24893882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24973;
CC Evidence={ECO:0000305|PubMed:21675912};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1S)-1,25-dihydroxy-24-oxocalciol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (1S)-1,23,25-trihydroxy-24-oxocalciol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:24976, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:47812, ChEBI:CHEBI:47813; EC=1.14.15.16;
CC Evidence={ECO:0000269|PubMed:16617161, ECO:0000269|PubMed:21675912,
CC ECO:0000269|PubMed:24893882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24977;
CC Evidence={ECO:0000305|PubMed:21675912};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1S)-1,23-dihydroxy-24,25,26,27-tetranorcalciol + 2 H(+) + O2
CC + 2 reduced [adrenodoxin] = (1S)-1-hydroxy-23-oxo-24,25,26,27-
CC tetranorcalciol + 2 H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:24984, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47818,
CC ChEBI:CHEBI:47820; EC=1.14.15.16;
CC Evidence={ECO:0000269|PubMed:21675912, ECO:0000269|PubMed:24893882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24985;
CC Evidence={ECO:0000305|PubMed:21675912};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + H(+) + O2
CC + 2 reduced [adrenodoxin] = calcitroate + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:24988, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47820,
CC ChEBI:CHEBI:58715; EC=1.14.15.16;
CC Evidence={ECO:0000269|PubMed:21675912, ECO:0000269|PubMed:24893882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24989;
CC Evidence={ECO:0000305|PubMed:21675912};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcitriol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC 1alpha,23S,25-trihydroxycholecalciferol + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:49192, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17823, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:90970; Evidence={ECO:0000269|PubMed:16617161,
CC ECO:0000269|PubMed:24893882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49193;
CC Evidence={ECO:0000305|PubMed:16617161};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = H2O + 2
CC oxidized [adrenodoxin] + secalciferol; Xref=Rhea:RHEA:24968,
CC Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17933,
CC ChEBI:CHEBI:28818, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
CC EC=1.14.15.16; Evidence={ECO:0000269|PubMed:11012668,
CC ECO:0000269|PubMed:15574355, ECO:0000269|PubMed:24893882,
CC ECO:0000269|PubMed:8679605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24969;
CC Evidence={ECO:0000305|PubMed:8679605};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + O2 + 2 reduced [adrenodoxin] + secalciferol = 25-
CC hydroxy-24-oxocalciol + 2 H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:49196, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28818, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:47805; Evidence={ECO:0000269|PubMed:11012668,
CC ECO:0000269|PubMed:24893882, ECO:0000269|PubMed:8679605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49197;
CC Evidence={ECO:0000305|PubMed:8679605};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=25-hydroxy-24-oxocalciol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 23S,25-dihydroxy-24-oxocholecalciferol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:49268, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:47805, ChEBI:CHEBI:90980;
CC Evidence={ECO:0000269|PubMed:11012668, ECO:0000269|PubMed:24893882,
CC ECO:0000269|PubMed:8679605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49269;
CC Evidence={ECO:0000305|PubMed:8679605};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (23S)-
CC 23,25-dihydroxycalciol + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:46616, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17933, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:47214; Evidence={ECO:0000269|PubMed:11012668,
CC ECO:0000269|PubMed:24893882, ECO:0000269|PubMed:8679605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46617;
CC Evidence={ECO:0000305|PubMed:8679605};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20S-hydroxycholecalciferol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 20S,25-dihydroxycholecalciferol + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:49212, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:90983,
CC ChEBI:CHEBI:90984; Evidence={ECO:0000269|PubMed:25727742};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49213;
CC Evidence={ECO:0000305|PubMed:25727742};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20S-hydroxycholecalciferol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 20S,24R-dihydroxycholecalciferol + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:49204, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:90983,
CC ChEBI:CHEBI:90985; Evidence={ECO:0000269|PubMed:25727742};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49205;
CC Evidence={ECO:0000305|PubMed:25727742};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20S,23-dihydroxycholecalciferol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 20S,23,25-trihydroxycholecalciferol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:49396, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:91306, ChEBI:CHEBI:91308;
CC Evidence={ECO:0000269|PubMed:25727742};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49397;
CC Evidence={ECO:0000305|PubMed:25727742};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 uM for calcidiol {ECO:0000269|PubMed:11012668};
CC KM=0.072 uM for calcitriol {ECO:0000269|PubMed:11012668};
CC KM=0.35 uM for calcitriol {ECO:0000269|PubMed:16617161};
CC Vmax=0.088 mol/min/mol enzyme toward calcidiol
CC {ECO:0000269|PubMed:11012668};
CC Vmax=0.066 mol/min/mol enzyme toward calcitriol
CC {ECO:0000269|PubMed:11012668};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q09128}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q07973-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q07973-2; Sequence=VSP_043101;
CC Name=3; Synonyms=CYP24-SV;
CC IsoId=Q07973-3; Sequence=VSP_053367, VSP_053368;
CC -!- DISEASE: Hypercalcemia, infantile, 1 (HCINF1) [MIM:143880]: A disorder
CC characterized by abnormally high level of calcium in the blood, failure
CC to thrive, vomiting, dehydration, and nephrocalcinosis.
CC {ECO:0000269|PubMed:21675912}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Specifically expressed in macrophages.
CC Lacks the transit peptide. May be a dominant negative-acting isoform
CC possibly by sequestering vitamin D metabolites. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; L13286; AAA62379.1; -; mRNA.
DR EMBL; AY858838; AAW50795.1; -; mRNA.
DR EMBL; AL138805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109083; AAI09084.1; -; mRNA.
DR EMBL; BC109084; AAI09085.1; -; mRNA.
DR EMBL; U60669; AAB03776.1; ALT_SEQ; Genomic_DNA.
DR EMBL; S67623; AAB29308.1; -; mRNA.
DR CCDS; CCDS33491.1; -. [Q07973-1]
DR CCDS; CCDS46616.1; -. [Q07973-2]
DR PIR; A47436; A47436.
DR PIR; I55488; I55488.
DR RefSeq; NP_000773.2; NM_000782.4. [Q07973-1]
DR RefSeq; NP_001122387.1; NM_001128915.1. [Q07973-2]
DR RefSeq; XP_005260361.1; XM_005260304.4. [Q07973-1]
DR RefSeq; XP_016883180.1; XM_017027691.1. [Q07973-1]
DR RefSeq; XP_016883181.1; XM_017027692.1. [Q07973-1]
DR RefSeq; XP_016883182.1; XM_017027693.1. [Q07973-2]
DR AlphaFoldDB; Q07973; -.
DR SMR; Q07973; -.
DR BioGRID; 107963; 102.
DR IntAct; Q07973; 6.
DR MINT; Q07973; -.
DR STRING; 9606.ENSP00000216862; -.
DR BindingDB; Q07973; -.
DR ChEMBL; CHEMBL4521; -.
DR DrugBank; DB00146; Calcifediol.
DR DrugBank; DB02300; Calcipotriol.
DR DrugBank; DB00136; Calcitriol.
DR DrugBank; DB01285; Corticotropin.
DR DrugBank; DB05024; CTA018.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00910; Paricalcitol.
DR DrugCentral; Q07973; -.
DR GuidetoPHARMACOLOGY; 1365; -.
DR SwissLipids; SLP:000001269; -.
DR iPTMnet; Q07973; -.
DR PhosphoSitePlus; Q07973; -.
DR BioMuta; CYP24A1; -.
DR DMDM; 19862747; -.
DR jPOST; Q07973; -.
DR MassIVE; Q07973; -.
DR MaxQB; Q07973; -.
DR PaxDb; Q07973; -.
DR PeptideAtlas; Q07973; -.
DR PRIDE; Q07973; -.
DR ProteomicsDB; 58564; -. [Q07973-1]
DR ProteomicsDB; 58565; -. [Q07973-2]
DR ProteomicsDB; 62973; -.
DR Antibodypedia; 13944; 325 antibodies from 36 providers.
DR DNASU; 1591; -.
DR Ensembl; ENST00000216862.8; ENSP00000216862.3; ENSG00000019186.10. [Q07973-1]
DR Ensembl; ENST00000395954.3; ENSP00000379284.3; ENSG00000019186.10. [Q07973-3]
DR Ensembl; ENST00000395955.7; ENSP00000379285.3; ENSG00000019186.10. [Q07973-2]
DR GeneID; 1591; -.
DR KEGG; hsa:1591; -.
DR MANE-Select; ENST00000216862.8; ENSP00000216862.3; NM_000782.5; NP_000773.2.
DR UCSC; uc002xwu.2; human. [Q07973-1]
DR CTD; 1591; -.
DR DisGeNET; 1591; -.
DR GeneCards; CYP24A1; -.
DR HGNC; HGNC:2602; CYP24A1.
DR HPA; ENSG00000019186; Group enriched (endometrium, kidney, lymphoid tissue, placenta, urinary bladder).
DR MalaCards; CYP24A1; -.
DR MIM; 126065; gene.
DR MIM; 143880; phenotype.
DR neXtProt; NX_Q07973; -.
DR OpenTargets; ENSG00000019186; -.
DR Orphanet; 300547; Autosomal recessive infantile hypercalcemia.
DR PharmGKB; PA27097; -.
DR VEuPathDB; HostDB:ENSG00000019186; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00950000182905; -.
DR HOGENOM; CLU_001570_28_1_1; -.
DR InParanoid; Q07973; -.
DR OMA; MQHRNVA; -.
DR OrthoDB; 1273535at2759; -.
DR PhylomeDB; Q07973; -.
DR TreeFam; TF105094; -.
DR BioCyc; MetaCyc:HS00395-MON; -.
DR BRENDA; 1.14.14.24; 2681.
DR BRENDA; 1.14.15.16; 2681.
DR PathwayCommons; Q07973; -.
DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-HSA-211916; Vitamins.
DR Reactome; R-HSA-5579010; Defective CYP24A1 causes HCAI.
DR SABIO-RK; Q07973; -.
DR SignaLink; Q07973; -.
DR SIGNOR; Q07973; -.
DR BioGRID-ORCS; 1591; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; CYP24A1; human.
DR GeneWiki; CYP24A1; -.
DR GenomeRNAi; 1591; -.
DR Pharos; Q07973; Tchem.
DR PRO; PR:Q07973; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q07973; protein.
DR Bgee; ENSG00000019186; Expressed in olfactory segment of nasal mucosa and 110 other tissues.
DR Genevisible; Q07973; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0062181; F:1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0030342; F:1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0062180; F:25-hydroxycholecalciferol-23-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0008403; F:25-hydroxycholecalciferol-24-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; TAS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0070643; F:vitamin D 25-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0010430; P:fatty acid omega-oxidation; IBA:GO_Central.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:BHF-UCL.
DR GO; GO:0033280; P:response to vitamin D; IDA:BHF-UCL.
DR GO; GO:0042369; P:vitamin D catabolic process; IDA:UniProtKB.
DR GO; GO:0042359; P:vitamin D metabolic process; TAS:Reactome.
DR GO; GO:0070561; P:vitamin D receptor signaling pathway; NAS:BHF-UCL.
DR GO; GO:0006766; P:vitamin metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Heme; Iron; Lipid metabolism;
KW Metal-binding; Mitochondrion; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q09128"
FT CHAIN 36..514
FT /note="1,25-dihydroxyvitamin D(3) 24-hydroxylase,
FT mitochondrial"
FT /id="PRO_0000003615"
FT BINDING 462
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q09128"
FT VAR_SEQ 1..8
FT /note="MSSPISKS -> MYSCFSHR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15788398"
FT /id="VSP_053367"
FT VAR_SEQ 9..150
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15788398"
FT /id="VSP_053368"
FT VAR_SEQ 413..478
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043101"
FT VARIANT 143
FT /note="Missing (in HCINF1; complete loss of function)"
FT /evidence="ECO:0000269|PubMed:21675912"
FT /id="VAR_066408"
FT VARIANT 157
FT /note="R -> Q (in dbSNP:rs35051736)"
FT /id="VAR_048464"
FT VARIANT 159
FT /note="R -> Q (in HCINF1; complete loss of function;
FT dbSNP:rs387907322)"
FT /evidence="ECO:0000269|PubMed:21675912"
FT /id="VAR_066409"
FT VARIANT 322
FT /note="E -> K (in HCINF1; complete loss of function;
FT dbSNP:rs387907324)"
FT /evidence="ECO:0000269|PubMed:21675912"
FT /id="VAR_066410"
FT VARIANT 374
FT /note="M -> T (in dbSNP:rs6022990)"
FT /id="VAR_048465"
FT VARIANT 396
FT /note="R -> W (in HCINF1; complete loss of function;
FT dbSNP:rs114368325)"
FT /evidence="ECO:0000269|PubMed:21675912"
FT /id="VAR_066411"
FT VARIANT 409
FT /note="L -> S (in HCINF1; retains small but measurable
FT levels of activity; dbSNP:rs6068812)"
FT /evidence="ECO:0000269|PubMed:21675912"
FT /id="VAR_048466"
FT CONFLICT 68
FT /note="G -> A (in Ref. 1; AAA62379/AAB03776)"
FT /evidence="ECO:0000305"
FT CONFLICT 124..125
FT /note="AY -> V (in Ref. 1; AAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="D -> G (in Ref. 1; AAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="V -> R (in Ref. 1; AAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="A -> E (in Ref. 1; AAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="S -> G (in Ref. 1; AAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="F -> S (in Ref. 6; AAB29308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 58875 MW; 8862F63771981195 CRC64;
MSSPISKSRS LAAFLQQLRS PRQPPRLVTS TAYTSPQPRE VPVCPLTAGG ETQNAAALPG
PTSWPLLGSL LQILWKGGLK KQHDTLVEYH KKYGKIFRMK LGSFESVHLG SPCLLEALYR
TESAYPQRLE IKPWKAYRDY RKEGYGLLIL EGEDWQRVRS AFQKKLMKPG EVMKLDNKIN
EVLADFMGRI DELCDERGHV EDLYSELNKW SFESICLVLY EKRFGLLQKN AGDEAVNFIM
AIKTMMSTFG RMMVTPVELH KSLNTKVWQD HTLAWDTIFK SVKACIDNRL EKYSQQPSAD
FLCDIYHQNR LSKKELYAAV TELQLAAVET TANSLMWILY NLSRNPQVQQ KLLKEIQSVL
PENQVPRAED LRNMPYLKAC LKESMRLTPS VPFTTRTLDK ATVLGEYALP KGTVLMLNTQ
VLGSSEDNFE DSSQFRPERW LQEKEKINPF AHLPFGVGKR MCIGRRLAEL QLHLALCWIV
RKYDIQATDN EPVEMLHSGT LVPSRELPIA FCQR
