ID CP24A_HUMAN Reviewed; 514 AA. AC Q07973; Q15807; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 18-OCT-2001, sequence version 2. DT 28-JUN-2011, entry version 99. DE RecName: Full=1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial; DE Short=24-OHase; DE Short=Vitamin D(3) 24-hydroxylase; DE EC=1.14.13.n4; DE AltName: Full=Cytochrome P450 24A1; DE AltName: Full=Cytochrome P450-CC24; DE Flags: Precursor; GN Name=CYP24A1; Synonyms=CYP24; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=93281615; 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- RT hydroxylase cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 90:4543-4547(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=21638749; 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., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA 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., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104. RX MEDLINE=95359195; PubMed=7632726; RA Chen K.-S., DeLuca H.F.; RT "Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase RT gene promoter and identification of two vitamin D-responsive RT elements."; RL Biochim. Biophys. Acta 1263:1-9(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 258-514. RX MEDLINE=94091187; PubMed=8266831; RA Labuda M., Lemieux N., Tihy F., Prinster C., Glorieux F.H.; RT "Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps RT to a different chromosomal location than that of pseudovitamin D- RT deficient rickets."; RL J. Bone Miner. Res. 8:1397-1406(1993). RN [5] RP 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). CC -!- FUNCTION: Has a role in maintaining calcium homeostasis. Catalyzes CC the NADPH-dependent 24-hydroxylation of calcidiol (25- CC hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin CC D(3)). The enzyme can perform up to 6 rounds of hydroxylation of CC calcitriol leading to calcitroic acid. It also shows 23- CC hydroxylating activity leading to 1-alpha,25-dihydroxyvitamin CC D(3)-26,23-lactone as end product. CC -!- CATALYTIC ACTIVITY: Calcitriol + NADPH + O(2) = calcitetrol + CC NADP(+) + H(2)O. CC -!- CATALYTIC ACTIVITY: Calcidiol + NADPH + O(2) = secalciferol + CC NADP(+) + H(2)O. CC -!- COFACTOR: Heme group (By similarity). CC -!- SUBCELLULAR LOCATION: Mitochondrion. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. 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; AL138805; CAB91829.1; -; Genomic_DNA. DR EMBL; U60669; AAB03776.1; ALT_SEQ; Genomic_DNA. DR EMBL; S67623; AAB29308.1; -; mRNA. DR IPI; IPI00020586; -. DR PIR; A47436; A47436. DR PIR; I55488; I55488. DR RefSeq; NP_000773.2; NM_000782.4. DR UniGene; Hs.89663; -. DR ProteinModelPortal; Q07973; -. DR SMR; Q07973; 51-514. DR STRING; Q07973; -. DR PhosphoSite; Q07973; -. DR PRIDE; Q07973; -. DR Ensembl; ENST00000216862; ENSP00000216862; ENSG00000019186. DR GeneID; 1591; -. DR KEGG; hsa:1591; -. DR UCSC; uc002xwv.2; human. DR CTD; 1591; -. DR GeneCards; GC20M049516; -. DR HGNC; HGNC:2602; CYP24A1. DR HPA; HPA022261; -. DR MIM; 126065; gene. DR neXtProt; NX_Q07973; -. DR PharmGKB; PA27097; -. DR eggNOG; prNOG09369; -. DR GeneTree; ENSGT00550000074304; -. DR HOGENOM; HBG443701; -. DR HOVERGEN; HBG099053; -. DR InParanoid; Q07973; -. DR OMA; EYHKKYG; -. DR OrthoDB; EOG4PC9RZ; -. DR PhylomeDB; Q07973; -. DR Reactome; REACT_11193; Metabolism of vitamins and cofactors. DR Reactome; REACT_13433; Biological oxidations. DR Reactome; REACT_15314; Hormone biosynthesis. DR Reactome; REACT_22258; Metabolism of lipids and lipoproteins. DR DrugBank; DB00146; Calcidiol. DR DrugBank; DB00136; Calcitriol. DR DrugBank; DB00169; Cholecalciferol. DR DrugBank; DB00153; Ergocalciferol. DR DrugBank; DB00910; Paricalcitol. DR NextBio; 6538; -. DR ArrayExpress; Q07973; -. DR Bgee; Q07973; -. DR CleanEx; HS_CYP24A1; -. DR Genevestigator; Q07973; -. DR GermOnline; ENSG00000019186; Homo sapiens. DR GO; GO:0005743; C:mitochondrial inner membrane; EXP:Reactome. DR GO; GO:0030342; F:1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity; IDA:UniProtKB. DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro. DR GO; GO:0020037; F:heme binding; TAS:UniProtKB. DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH as one donor, and incorporation of one atom of oxygen; IEA:EC. DR GO; GO:0042446; P:hormone biosynthetic process; TAS:Reactome. DR GO; GO:0001649; P:osteoblast differentiation; IEP:BHF-UCL. DR GO; GO:0042369; P:vitamin D catabolic process; NAS:BHF-UCL. DR GO; GO:0070561; P:vitamin D receptor signaling pathway; IEP:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR Gene3D; G3DSA:1.10.630.10; Cyt_P450; 1. 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 2: Evidence at transcript level; KW Complete proteome; Heme; Iron; Metal-binding; Mitochondrion; KW Monooxygenase; NADP; Oxidoreductase; Polymorphism; Transit peptide. FT TRANSIT 1 35 Mitochondrion (By similarity). FT CHAIN 36 514 1,25-dihydroxyvitamin D(3) 24- FT hydroxylase, mitochondrial. FT /FTId=PRO_0000003615. FT METAL 462 462 Iron (heme axial ligand) (Potential). FT VARIANT 157 157 R -> Q (in dbSNP:rs35051736). FT /FTId=VAR_048464. FT VARIANT 374 374 M -> T (in dbSNP:rs6022990). FT /FTId=VAR_048465. FT VARIANT 409 409 L -> S (in dbSNP:rs6068812). FT /FTId=VAR_048466. FT CONFLICT 68 68 G -> A (in Ref. 1; AAA62379/AAB03776). FT CONFLICT 124 125 AY -> V (in Ref. 1; AAA62379). FT CONFLICT 270 270 D -> G (in Ref. 1; AAA62379). FT CONFLICT 365 365 V -> R (in Ref. 1; AAA62379). FT CONFLICT 368 368 A -> E (in Ref. 1; AAA62379). FT CONFLICT 390 390 S -> G (in Ref. 1; AAA62379). FT CONFLICT 511 511 F -> S (in Ref. 4; AAB29308). 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 //