CP24A_MOUSE
ID CP24A_MOUSE Reviewed; 514 AA.
AC Q64441;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial;
DE Short=24-OHase;
DE Short=Vitamin D(3) 24-hydroxylase;
DE EC=1.14.15.16 {ECO:0000250|UniProtKB:Q09128};
DE AltName: Full=Cytochrome P450 24A1;
DE AltName: Full=Cytochrome P450-CC24;
DE Flags: Precursor;
GN Name=Cyp24a1 {ECO:0000312|MGI:MGI:88593}; Synonyms=Cyp-24, Cyp24;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=7578252; DOI=10.1016/0167-4781(95)00147-9;
RA Itoh S., Yoshimura T., Iemura O., Yamada E., Tsujikawa K., Kohama Y.,
RA Mimura T.;
RT "Molecular cloning of 25-hydroxyvitamin D-3 24-hydroxylase (Cyp-24) from
RT mouse kidney: its inducibility by vitamin D-3.";
RL Biochim. Biophys. Acta 1264:26-28(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ddY; TISSUE=Kidney;
RX PubMed=9165006; DOI=10.1210/endo.138.6.5170;
RA Akeno N., Saikatsu S., Kawane T., Horiuchi N.;
RT "Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution,
RT and transcriptional regulation by 1alpha,25-dihydroxyvitamin D3.";
RL Endocrinology 138:2233-2240(1997).
RN [3]
RP INDUCTION.
RX PubMed=14528024; DOI=10.1210/me.2003-0048;
RA Tsujikawa H., Kurotaki Y., Fujimori T., Fukuda K., Nabeshima Y.;
RT "Klotho, a gene related to a syndrome resembling human premature aging,
RT functions in a negative regulatory circuit of vitamin D endocrine system.";
RL Mol. Endocrinol. 17:2393-2403(2003).
CC -!- FUNCTION: A cytochrome P450 monooxygenase with a key role in vitamin D
CC catabolism and calcium homeostasis. Via C24-oxidation pathway,
CC catalyzes the inactivation of both the vitamin D precursor calcidiol
CC (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-
CC dihydroxyvitamin D(3)). With initial hydroxylation at C-24 (via C24-
CC oxidation pathway), performs a sequential 6-step oxidation of
CC calcitriol leading to the formation of the biliary metabolite
CC calcitroic acid. Hydroxylates at C-24 or C-25 other vitamin D active
CC metabolites, such as CYP11A1-derived secosteroids 20S-
CC hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol.
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via FDXR/adrenodoxin reductase and
CC FDX1/adrenodoxin. {ECO:0000250|UniProtKB:Q09128}.
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24965;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24973;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24977;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24985;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24989;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24969;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49197;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49269;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49397;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20S,23-dihydroxycholecalciferol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 20S,23,24-trihydroxycholecalciferol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:49392, 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:91307;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49393;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49213;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20S-hydroxycholecalciferol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = 20S,24S-dihydroxycholecalciferol + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:49208, 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:90986; Evidence={ECO:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49209;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
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:0000250|UniProtKB:Q09128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49205;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q09128};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q09128}.
CC -!- INDUCTION: By 1,25-dihydroxyvitamin D(3) in kidney.
CC {ECO:0000269|PubMed:14528024}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D49438; BAA08416.1; -; mRNA.
DR EMBL; D89669; BAA21843.1; -; mRNA.
DR CCDS; CCDS17122.1; -.
DR PIR; S60033; S60033.
DR RefSeq; NP_034126.1; NM_009996.4.
DR AlphaFoldDB; Q64441; -.
DR SMR; Q64441; -.
DR BioGRID; 199006; 14.
DR STRING; 10090.ENSMUSP00000047954; -.
DR iPTMnet; Q64441; -.
DR PhosphoSitePlus; Q64441; -.
DR EPD; Q64441; -.
DR PaxDb; Q64441; -.
DR PRIDE; Q64441; -.
DR ProteomicsDB; 283437; -.
DR Antibodypedia; 13944; 325 antibodies from 36 providers.
DR DNASU; 13081; -.
DR Ensembl; ENSMUST00000038824; ENSMUSP00000047954; ENSMUSG00000038567.
DR GeneID; 13081; -.
DR KEGG; mmu:13081; -.
DR UCSC; uc008ocb.1; mouse.
DR CTD; 1591; -.
DR MGI; MGI:88593; Cyp24a1.
DR VEuPathDB; HostDB:ENSMUSG00000038567; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00950000182905; -.
DR HOGENOM; CLU_001570_28_1_1; -.
DR InParanoid; Q64441; -.
DR OMA; MQHRNVA; -.
DR OrthoDB; 1273535at2759; -.
DR PhylomeDB; Q64441; -.
DR TreeFam; TF105094; -.
DR Reactome; R-MMU-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-MMU-211916; Vitamins.
DR BioGRID-ORCS; 13081; 4 hits in 75 CRISPR screens.
DR PRO; PR:Q64441; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q64441; protein.
DR Bgee; ENSMUSG00000038567; Expressed in right kidney and 15 other tissues.
DR ExpressionAtlas; Q64441; baseline and differential.
DR Genevisible; Q64441; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0062181; F:1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity; ISO:MGI.
DR GO; GO:0030342; F:1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0062180; F:25-hydroxycholecalciferol-23-hydroxylase activity; ISO:MGI.
DR GO; GO:0008403; F:25-hydroxycholecalciferol-24-hydroxylase activity; IMP:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0070576; F:vitamin D 24-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0070643; F:vitamin D 25-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0010430; P:fatty acid omega-oxidation; IBA:GO_Central.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; ISO:MGI.
DR GO; GO:0042369; P:vitamin D catabolic process; ISS:UniProtKB.
DR GO; GO:0042359; P:vitamin D metabolic process; IMP:MGI.
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 2: Evidence at transcript level;
KW Heme; Iron; Lipid metabolism; Metal-binding; Mitochondrion; Monooxygenase;
KW Oxidoreductase; 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_0000003616"
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"
SQ SEQUENCE 514 AA; 59453 MW; 3D38BA9235177A42 CRC64;
MSCPIDKRRP LIAFLRRLRD LGQPPRSVTS KAHVKRAPKE VPLCPLMTDG ETRNVTSLPG
PTNWPLLGSL LEIFWKGGLK KQHDTLAEYH KKYGQIFRMK LGSFDSVHLG SPSLLEALYR
TESAHPQRLE IKPWKAYRDH RNEAYGLMIL EGQEWQRVRS AFQKKLMKPV EIMKLDKKIN
EVLADFMGQI DELRDERGRI QDLYSELNKW SFESICLVLY EKRFGLLQKD TEEEALTFIA
AIKTMMSTFG KMMVTPVELH KRLNTKVWQA HTLAWDTIFK SVKPCIDHRL ERYSQQPGAD
FLCDIYQQDH LSKKELYAAV TELQLAAVET TANSLMWILY NLSRNPQVQQ RLLREIQSVL
PDNQTPRAED VRNMPYLKAC LKESMRLTPS VPFTTRTLDK PTVLGEYTLP KGTVLTLNTQ
VLGSSEDNFE DADKFRPERW LEKEKKINPF AHLPFGVGKR MCIGRRLAEL QLHLALCWII
QKYNIVATDS EPVEMLHLGI LVPSRELPIA FCPR
