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 14-DEC-2022, entry version 195. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ProteomicsDB; 58564; -. [Q07973-1] DR ProteomicsDB; 58565; -. [Q07973-2] DR ProteomicsDB; 62973; -. DR Antibodypedia; 13944; 324 antibodies from 35 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 AGR; HGNC:2602; -. 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; Cytochrome P450; 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 //