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1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (24-OHase) (Vitamin D(3) 24-hydroxylase) (EC 1.14.15.16) (Cytochrome P450 24A1) (Cytochrome P450-CC24)

 CP24A_RAT               Reviewed;         514 AA.
Q09128; Q498V4; Q63685;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
13-NOV-2019, entry version 134.
RecName: Full=1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial;
Short=24-OHase;
Short=Vitamin D(3) 24-hydroxylase;
EC=1.14.15.16 {ECO:0000269|PubMed:2026586};
AltName: Full=Cytochrome P450 24A1;
AltName: Full=Cytochrome P450-CC24;
Flags: Precursor;
Name=Cyp24a1; Synonyms=Cyp24;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 36-43.
TISSUE=Kidney;
PubMed=1991512; DOI=10.1016/0014-5793(91)80115-j;
Ohyama Y., Noshiro M., Okuda K.;
"Cloning and expression of cDNA encoding 25-hydroxyvitamin D3 24-
hydroxylase.";
FEBS Lett. 278:195-198(1991).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=8418863; DOI=10.1021/bi00052a011;
Ohyama Y., Noshiro M., Eggertsen G., Gotoh O., Kato Y., Bjoerkhem I.,
Okuda K.;
"Structural characterization of the gene encoding rat 25-
hydroxyvitamin D3 24-hydroxylase.";
Biochemistry 32:76-82(1993).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Kidney;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-86.
PubMed=8036172; DOI=10.1093/nar/22.12.2410;
Hahn C.N., Kerry D.M., Omdahl J.L., May B.K.;
"Identification of a vitamin D responsive element in the promoter of
the rat cytochrome P450(24) gene.";
Nucleic Acids Res. 22:2410-2416(1994).
[5]
PROTEIN SEQUENCE OF 36-43, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE
SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=2026586;
Ohyama Y., Okuda K.;
"Isolation and characterization of a cytochrome P-450 from rat kidney
mitochondria that catalyzes the 24-hydroxylation of 25-hydroxyvitamin
D3.";
J. Biol. Chem. 266:8690-8695(1991).
[6]
SUBSTRATE SPECIFICITY.
PubMed=15574355; DOI=10.2741/1514;
Sakaki T., Kagawa N., Yamamoto K., Inouye K.;
"Metabolism of vitamin D3 by cytochromes P450.";
Front. Biosci. 10:119-134(2005).
[7]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 34-514 IN COMPLEX WITH HEME,
AND COFACTOR.
PubMed=19961857; DOI=10.1016/j.jmb.2009.11.057;
Annalora A.J., Goodin D.B., Hong W.X., Zhang Q., Johnson E.F.,
Stout C.D.;
"Crystal structure of CYP24A1, a mitochondrial cytochrome P450
involved in vitamin D metabolism.";
J. Mol. Biol. 396:441-451(2010).
-!- FUNCTION: Has a role in maintaining calcium homeostasis. Catalyzes
the adrenodoxin-dependent 24-hydroxylation of calcidiol (25-
hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin
D(3)). The enzyme can perform up to 6 rounds of hydroxylation of
calcitriol leading to calcitroic acid.
{ECO:0000269|PubMed:2026586}.
-!- CATALYTIC ACTIVITY:
Reaction=calcitriol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
calcitetrol + H2O + 2 oxidized [adrenodoxin];
Xref=Rhea:RHEA:24964, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
ChEBI:CHEBI:17823, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
ChEBI:CHEBI:47799; EC=1.14.15.16;
Evidence={ECO:0000269|PubMed:2026586};
-!- CATALYTIC ACTIVITY:
Reaction=calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = H2O +
2 oxidized [adrenodoxin] + secalciferol; Xref=Rhea:RHEA:24968,
Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17933,
ChEBI:CHEBI:28818, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
EC=1.14.15.16; Evidence={ECO:0000269|PubMed:2026586};
-!- COFACTOR:
Name=heme; Xref=ChEBI:CHEBI:30413;
Evidence={ECO:0000269|PubMed:19961857};
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=2.8 uM for calcidiol {ECO:0000269|PubMed:2026586};
pH dependence:
Optimum pH is 7.7. {ECO:0000269|PubMed:2026586};
-!- SUBCELLULAR LOCATION: Mitochondrion.
-!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; X59506; CAA42093.1; -; mRNA.
EMBL; L04618; AAA42340.1; -; Genomic_DNA.
EMBL; L04608; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04609; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04610; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04611; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04612; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04613; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04614; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04615; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04616; AAA42340.1; JOINED; Genomic_DNA.
EMBL; L04617; AAA42340.1; JOINED; Genomic_DNA.
EMBL; BC100059; AAI00060.1; -; mRNA.
EMBL; Z28351; CAA82206.1; -; Genomic_DNA.
PIR; A45228; A45228.
RefSeq; NP_963966.1; NM_201635.3.
PDB; 3K9V; X-ray; 2.50 A; A/B=34-514.
PDB; 3K9Y; X-ray; 2.80 A; A/B=34-514.
PDBsum; 3K9V; -.
PDBsum; 3K9Y; -.
SMR; Q09128; -.
STRING; 10116.ENSRNOP00000043298; -.
BindingDB; Q09128; -.
ChEMBL; CHEMBL3748; -.
DrugCentral; Q09128; -.
SwissLipids; SLP:000001482; -.
PaxDb; Q09128; -.
PRIDE; Q09128; -.
Ensembl; ENSRNOT00000046011; ENSRNOP00000043298; ENSRNOG00000013062.
GeneID; 25279; -.
KEGG; rno:25279; -.
CTD; 1591; -.
RGD; 2462; Cyp24a1.
eggNOG; KOG0159; Eukaryota.
eggNOG; COG2124; LUCA.
GeneTree; ENSGT00950000182905; -.
HOGENOM; HOG000276540; -.
InParanoid; Q09128; -.
KO; K07436; -.
OMA; HIGAPCL; -.
OrthoDB; 1273535at2759; -.
PhylomeDB; Q09128; -.
TreeFam; TF105094; -.
BioCyc; MetaCyc:MONOMER-14357; -.
Reactome; R-RNO-196791; Vitamin D (calciferol) metabolism.
Reactome; R-RNO-211916; Vitamins.
SABIO-RK; Q09128; -.
EvolutionaryTrace; Q09128; -.
PRO; PR:Q09128; -.
Proteomes; UP000002494; Chromosome 3.
Bgee; ENSRNOG00000013062; Expressed in 2 organ(s), highest expression level in adult mammalian kidney.
GO; GO:0005739; C:mitochondrion; TAS:RGD.
GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
GO; GO:0030342; F:1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity; TAS:BHF-UCL.
GO; GO:0008403; F:25-hydroxycholecalciferol-24-hydroxylase activity; IDA:RGD.
GO; GO:0020037; F:heme binding; IEA:InterPro.
GO; GO:0005506; F:iron ion binding; IEA:InterPro.
GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
GO; GO:0042369; P:vitamin D catabolic process; TAS:RGD.
GO; GO:0042359; P:vitamin D metabolic process; IDA:RGD.
Gene3D; 1.10.630.10; -; 1.
InterPro; IPR001128; Cyt_P450.
InterPro; IPR017972; Cyt_P450_CS.
InterPro; IPR002949; Cyt_P450_E_CYP24A_mit.
InterPro; IPR036396; Cyt_P450_sf.
Pfam; PF00067; p450; 1.
PRINTS; PR01238; MITP450CC24.
PRINTS; PR00385; P450.
SUPFAM; SSF48264; SSF48264; 1.
PROSITE; PS00086; CYTOCHROME_P450; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Direct protein sequencing; Heme;
Iron; Metal-binding; Mitochondrion; Monooxygenase; Oxidoreductase;
Reference proteome; Transit peptide.
TRANSIT 1 35 Mitochondrion.
{ECO:0000269|PubMed:1991512,
ECO:0000269|PubMed:2026586}.
CHAIN 36 514 1,25-dihydroxyvitamin D(3) 24-
hydroxylase, mitochondrial.
/FTId=PRO_0000003617.
METAL 462 462 Iron (heme axial ligand).
HELIX 55 57 {ECO:0000244|PDB:3K9V}.
TURN 65 67 {ECO:0000244|PDB:3K9V}.
HELIX 70 75 {ECO:0000244|PDB:3K9V}.
HELIX 79 81 {ECO:0000244|PDB:3K9V}.
HELIX 82 93 {ECO:0000244|PDB:3K9V}.
STRAND 95 101 {ECO:0000244|PDB:3K9V}.
STRAND 104 109 {ECO:0000244|PDB:3K9V}.
HELIX 112 120 {ECO:0000244|PDB:3K9V}.
HELIX 132 141 {ECO:0000244|PDB:3K9V}.
TURN 147 149 {ECO:0000244|PDB:3K9V}.
HELIX 152 166 {ECO:0000244|PDB:3K9V}.
HELIX 169 172 {ECO:0000244|PDB:3K9V}.
HELIX 173 175 {ECO:0000244|PDB:3K9V}.
HELIX 176 193 {ECO:0000244|PDB:3K9V}.
STRAND 196 198 {ECO:0000244|PDB:3K9Y}.
HELIX 203 220 {ECO:0000244|PDB:3K9V}.
STRAND 226 228 {ECO:0000244|PDB:3K9V}.
HELIX 236 246 {ECO:0000244|PDB:3K9V}.
HELIX 249 252 {ECO:0000244|PDB:3K9V}.
STRAND 253 255 {ECO:0000244|PDB:3K9V}.
HELIX 257 263 {ECO:0000244|PDB:3K9V}.
HELIX 266 292 {ECO:0000244|PDB:3K9V}.
TURN 293 295 {ECO:0000244|PDB:3K9V}.
HELIX 301 308 {ECO:0000244|PDB:3K9V}.
HELIX 313 343 {ECO:0000244|PDB:3K9V}.
HELIX 346 359 {ECO:0000244|PDB:3K9V}.
HELIX 368 373 {ECO:0000244|PDB:3K9V}.
HELIX 375 387 {ECO:0000244|PDB:3K9V}.
STRAND 393 397 {ECO:0000244|PDB:3K9V}.
STRAND 402 404 {ECO:0000244|PDB:3K9V}.
STRAND 407 409 {ECO:0000244|PDB:3K9V}.
STRAND 414 418 {ECO:0000244|PDB:3K9V}.
HELIX 421 424 {ECO:0000244|PDB:3K9V}.
TURN 426 428 {ECO:0000244|PDB:3K9V}.
STRAND 432 434 {ECO:0000244|PDB:3K9Y}.
HELIX 437 440 {ECO:0000244|PDB:3K9V}.
HELIX 449 451 {ECO:0000244|PDB:3K9V}.
HELIX 465 482 {ECO:0000244|PDB:3K9V}.
STRAND 483 488 {ECO:0000244|PDB:3K9V}.
STRAND 495 506 {ECO:0000244|PDB:3K9V}.
STRAND 509 513 {ECO:0000244|PDB:3K9V}.
SEQUENCE 514 AA; 59448 MW; 2E5CC1CCBA3C2B91 CRC64;
MSCPIDKRRT LIAFLRRLRD LGQPPRSVTS KASASRAPKE VPLCPLMTDG ETRNVTSLPG
PTNWPLLGSL LEIFWKGGLK KQHDTLAEYH KKYGQIFRMK LGSFDSVHLG SPSLLEALYR
TESAHPQRLE IKPWKAYRDH RNEAYGLMIL EGQEWQRVRS AFQKKLMKPV EIMKLDKKIN
EVLADFLERM DELCDERGRI PDLYSELNKW SFESICLVLY EKRFGLLQKE TEEEALTFIT
AIKTMMSTFG KMMVTPVELH KRLNTKVWQA HTLAWDTIFK SVKPCIDNRL QRYSQQPGAD
FLCDIYQQDH LSKKELYAAV TELQLAAVET TANSLMWILY NLSRNPQAQR RLLQEVQSVL
PDNQTPRAED LRNMPYLKAC LKESMRLTPS VPFTTRTLDK PTVLGEYALP KGTVLTLNTQ
VLGSSEDNFE DSHKFRPERW LQKEKKINPF AHLPFGIGKR MCIGRRLAEL QLHLALCWII
QKYDIVATDN EPVEMLHLGI LVPSRELPIA FRPR


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[CYP11B2] Cytochrome P450 11B2, mitochondrial (Aldosterone synthase) (ALDOS) (Aldosterone-synthesizing enzyme) (CYPXIB2) (Corticosterone 18-monooxygenase, CYP11B2) (EC 1.14.15.5) (Cytochrome P-450Aldo) (Cytochrome P-450C18) (Steroid 11-beta-hydroxylase, CYP11B2) (EC 1.14.15.4) (Steroid 18-hydroxylase)
[CYP11B1 S11BH] Cytochrome P450 11B1, mitochondrial (CYPXIB1) (Cytochrome P-450c11) (Cytochrome P450C11) (Steroid 11-beta-hydroxylase, CYP11B1) (EC 1.14.15.4)
[Cyp1a2 Cyp1a-2] Cytochrome P450 1A2 (EC 1.14.14.1) (CYPIA2) (Cholesterol 25-hydroxylase) (Cytochrome P-448) (Cytochrome P-450d) (Cytochrome P450-D) (Hydroperoxy icosatetraenoate dehydratase) (EC 4.2.1.152)
[Cyp11b2 Cyp11b-2] Cytochrome P450 11B2, mitochondrial (Aldosterone synthase) (ALDOS) (Aldosterone-synthesizing enzyme) (CYPXIB2) (Corticosterone 18-monooxygenase, CYP11B2) (EC 1.14.15.5) (Cytochrome P-450Aldo) (Cytochrome P-450C18) (Cytochrome P450C11) (Steroid 11-beta-hydroxylase, CYP11B2) (EC 1.14.15.4) (Steroid 18-hydroxylase)
[CYP2A6 CYP2A3] Cytochrome P450 2A6 (EC 1.14.13.-) (1,4-cineole 2-exo-monooxygenase) (CYPIIA6) (Coumarin 7-hydroxylase) (Cytochrome P450 IIA3) (Cytochrome P450(I))
[CYP4F2] Cytochrome P450 4F2 (EC 1.14.14.1) (20-hydroxyeicosatetraenoic acid synthase) (20-HETE synthase) (Arachidonic acid omega-hydroxylase) (CYPIVF2) (Cytochrome P450-LTB-omega) (Docosahexaenoic acid omega-hydroxylase) (EC 1.14.14.79) (Leukotriene-B(4) 20-monooxygenase 1) (Leukotriene-B(4) omega-hydroxylase 1) (EC 1.14.14.94) (Phylloquinone omega-hydroxylase CYP4F2) (EC 1.14.14.78)
[Cyp11b2 Cyp11b-2] Cytochrome P450 11B2, mitochondrial (Aldosterone synthase) (ALDOS) (Aldosterone-synthesizing enzyme) (CYPXIB2) (Corticosterone 18-monooxygenase, CYP11B2) (EC 1.14.15.5) (Cytochrome P-450Aldo) (Cytochrome P-450C18) (Cytochrome P450-Aldo-1) (Steroid 11-beta-hydroxylase, CYP11B2) (EC 1.14.15.4) (Steroid 18-hydroxylase)
[vdh] Vitamin D(3) 25-hydroxylase (EC 1.14.15.15) (Cytochrome P450)
[Cyp2d4 Cyp2d-18 Cyp2d-4 Cyp2d18] Cytochrome P450 2D4 (EC 1.14.14.1) (CYPIID18) (CYPIID4) (Cytochrome P450 2D-29) (Cytochrome P450 2D-35) (Cytochrome P450 2D18) (Cytochrome P450-CMF3) (Cytochrome P450-DB4) (Debrisoquine 4-hydroxylase)
[Cyp1a2 Cyp1a-2] Cytochrome P450 1A2 (EC 1.14.14.1) (CYPIA2) (Cholesterol 25-hydroxylase) (Cytochrome P450-P2) (Cytochrome P450-P3) (Hydroperoxy icosatetraenoate dehydratase) (EC 4.2.1.152)
[Cyp2a4 Cyp2a-4] Cytochrome P450 2A4 (EC 1.14.14.1) (CYPIIA4) (Cytochrome P450-15-alpha) (Cytochrome P450-IIA3.1) (Testosterone 15-alpha-hydroxylase)
[CYP21 CYP21A1 CYP21A2] Steroid 21-hydroxylase (EC 1.14.14.16) (21-OHase) (Cytochrome P-450c21) (Cytochrome P450 21) (Cytochrome P450 XXI) (Cytochrome P450-C21)
[Cyp11b1 Cyp11b-1] Cytochrome P450 11B1, mitochondrial (CYPXIB1) (Cytochrome P450(11 beta)-DS) (Cytochrome P450C11) (Steroid 11-beta-hydroxylase, CYP11B1) (EC 1.14.15.4)
[CYP17A1 CYP17 S17AH] Steroid 17-alpha-hydroxylase/17,20 lyase (EC 1.14.14.19) (17-alpha-hydroxyprogesterone aldolase) (EC 1.14.14.32) (CYPXVII) (Cytochrome P450 17A1) (Cytochrome P450-C17) (Cytochrome P450c17) (Steroid 17-alpha-monooxygenase)
[CYP2C19] Cytochrome P450 2C19 (EC 1.14.14.1) ((R)-limonene 6-monooxygenase) (EC 1.14.14.53) ((S)-limonene 6-monooxygenase) (EC 1.14.14.51) ((S)-limonene 7-monooxygenase) (EC 1.14.14.52) (CYPIIC17) (CYPIIC19) (Cytochrome P450-11A) (Cytochrome P450-254C) (Fenbendazole monooxygenase (4'-hydroxylating)) (EC 1.14.14.75) (Mephenytoin 4-hydroxylase)
[Cyp2a5 Cyp2a-5] Cytochrome P450 2A5 (EC 1.14.14.1) (CYPIIA5) (Coumarin 7-hydroxylase) (Cytochrome P450-15-COH) (Cytochrome P450-IIA3.2)
[Cyp2d1 Cyp2d-1 Cyp2d9] Cytochrome P450 2D1 (EC 1.14.14.1) (CYPIID1) (Cytochrome P450-CMF1A) (Cytochrome P450-DB1) (Cytochrome P450-UT-7) (Debrisoquine 4-hydroxylase)

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