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Q07973 (CP24A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Short name=24-OHase
Short name=Vitamin D(3) 24-hydroxylase
EC=1.14.13.126
Alternative name(s):
Cytochrome P450 24A1
Cytochrome P450-CC24
Gene names
Name:CYP24A1
Synonyms:CYP24
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length514 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of calcidiol (25-hydroxyvitamin D3) and calcitriol (1-alpha,25-dihydroxyvitamin D3). The enzyme can perform up to 6 rounds of hydroxylation of calcitriol leading to calcitroic acid. It also shows 23-hydroxylating activity leading to 1-alpha,25-dihydroxyvitamin D(3)-26,23-lactone as end product.

Catalytic activity

Calcitriol + NADPH + O2 = calcitetrol + NADP+ + H2O.

Calcidiol + NADPH + O2 = secalciferol + NADP+ + H2O.

Cofactor

Heme group By similarity.

Subcellular location

Mitochondrion.

Involvement in disease

Hypercalcemia infantile (HCAI) [MIM:143880]: A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processosteoblast differentiation

Inferred from expression pattern PubMed 17023519. Source: BHF-UCL

oxidation-reduction process

Inferred from direct assay Ref.1. Source: UniProtKB

response to vitamin D

Inferred from direct assay PubMed 16720713. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement. Source: Reactome

vitamin D catabolic process

Non-traceable author statement PubMed 16720713. Source: BHF-UCL

vitamin D metabolic process

Traceable author statement. Source: Reactome

vitamin D receptor signaling pathway

Non-traceable author statement PubMed 16720713. Source: BHF-UCL

vitamin metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Traceable author statement. Source: Reactome

   Molecular_function1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity

Inferred from direct assay Ref.1. Source: UniProtKB

25-hydroxycholecalciferol-24-hydroxylase activity

Inferred from electronic annotation. Source: Ensembl

heme binding

Traceable author statement Ref.1. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity

Non-traceable author statement Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q07973-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q07973-2)

The sequence of this isoform differs from the canonical sequence as follows:
     413-478: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q07973-3)

Also known as: CYP24-SV;

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MSSPISKS → MYSCFSHR
     9-150: Missing.
Note: Specifically expressed in macrophages. Lacks the transit peptide. May be a dominant negative-acting isoform possibly by sequestering vitamin D metabolites.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3535Mitochondrion By similarity
Chain36 – 5144791,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
PRO_0000003615

Sites

Metal binding4621Iron (heme axial ligand) By similarity

Natural variations

Alternative sequence1 – 88MSSPISKS → MYSCFSHR in isoform 3.
VSP_053367
Alternative sequence9 – 150142Missing in isoform 3.
VSP_053368
Alternative sequence413 – 47866Missing in isoform 2.
VSP_043101
Natural variant1431Missing in HCAI; complete loss of function. Ref.8
VAR_066408
Natural variant1571R → Q.
Corresponds to variant rs35051736 [ dbSNP | Ensembl ].
VAR_048464
Natural variant1591R → Q in HCAI; complete loss of function. Ref.8
VAR_066409
Natural variant3221E → K in HCAI; complete loss of function. Ref.8
VAR_066410
Natural variant3741M → T.
Corresponds to variant rs6022990 [ dbSNP | Ensembl ].
VAR_048465
Natural variant3961R → W in HCAI; complete loss of function. Ref.8
Corresponds to variant rs114368325 [ dbSNP | Ensembl ].
VAR_066411
Natural variant4091L → S in HCAI; retains small but measurable levels of activity. Ref.8
Corresponds to variant rs6068812 [ dbSNP | Ensembl ].
VAR_048466

Experimental info

Sequence conflict681G → A in AAA62379. Ref.1
Sequence conflict681G → A in AAB03776. Ref.1
Sequence conflict124 – 1252AY → V in AAA62379. Ref.1
Sequence conflict2701D → G in AAA62379. Ref.1
Sequence conflict3651V → R in AAA62379. Ref.1
Sequence conflict3681A → E in AAA62379. Ref.1
Sequence conflict3901S → G in AAA62379. Ref.1
Sequence conflict5111F → S in AAB29308. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 18, 2001. Version 2.
Checksum: 8862F63771981195

FASTA51458,875
        10         20         30         40         50         60 
MSSPISKSRS LAAFLQQLRS PRQPPRLVTS TAYTSPQPRE VPVCPLTAGG ETQNAAALPG 

        70         80         90        100        110        120 
PTSWPLLGSL LQILWKGGLK KQHDTLVEYH KKYGKIFRMK LGSFESVHLG SPCLLEALYR 

       130        140        150        160        170        180 
TESAYPQRLE IKPWKAYRDY RKEGYGLLIL EGEDWQRVRS AFQKKLMKPG EVMKLDNKIN 

       190        200        210        220        230        240 
EVLADFMGRI DELCDERGHV EDLYSELNKW SFESICLVLY EKRFGLLQKN AGDEAVNFIM 

       250        260        270        280        290        300 
AIKTMMSTFG RMMVTPVELH KSLNTKVWQD HTLAWDTIFK SVKACIDNRL EKYSQQPSAD 

       310        320        330        340        350        360 
FLCDIYHQNR LSKKELYAAV TELQLAAVET TANSLMWILY NLSRNPQVQQ KLLKEIQSVL 

       370        380        390        400        410        420 
PENQVPRAED LRNMPYLKAC LKESMRLTPS VPFTTRTLDK ATVLGEYALP KGTVLMLNTQ 

       430        440        450        460        470        480 
VLGSSEDNFE DSSQFRPERW LQEKEKINPF AHLPFGVGKR MCIGRRLAEL QLHLALCWIV 

       490        500        510 
RKYDIQATDN EPVEMLHSGT LVPSRELPIA FCQR 

« Hide

Isoform 2 [UniParc].

Checksum: 7A4DF62B195B6F9B
Show »

FASTA44851,207
Isoform 3 (CYP24-SV) [UniParc].

Checksum: 943689E132C4FE3B
Show »

FASTA37243,051

References

« Hide 'large scale' references
[1]"Isolation and expression of human 1,25-dihydroxyvitamin D3 24-hydroxylase cDNA."
Chen K.-S., Prahl J.M., Deluca H.F.
Proc. Natl. Acad. Sci. U.S.A. 90:4543-4547(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis."
Ren S., Nguyen L., Wu S., Encinas C., Adams J.S., Hewison M.
J. Biol. Chem. 280:20604-20611(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]"Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements."
Chen K.-S., DeLuca H.F.
Biochim. Biophys. Acta 1263:1-9(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104.
[6]"Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps to a different chromosomal location than that of pseudovitamin D-deficient rickets."
Labuda M., Lemieux N., Tihy F., Prinster C., Glorieux F.H.
J. Bone Miner. Res. 8:1397-1406(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 258-514 (ISOFORM 1).
[7]"Metabolism of vitamin D3 by cytochromes P450."
Sakaki T., Kagawa N., Yamamoto K., Inouye K.
Front. Biosci. 10:119-134(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE SPECIFICITY.
[8]"Mutations in CYP24A1 and idiopathic infantile hypercalcemia."
Schlingmann K.P., Kaufmann M., Weber S., Irwin A., Goos C., John U., Misselwitz J., Klaus G., Kuwertz-Broking E., Fehrenbach H., Wingen A.M., Guran T., Hoenderop J.G., Bindels R.J., Prosser D.E., Jones G., Konrad M.
N. Engl. J. Med. 365:410-421(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HCAI GLU-143 DEL; GLN-159; LYS-322; TRP-396 AND SER-409, CHARACTERIZATION OF VARIANTS HCAI GLU-143 DEL; GLN-159; LYS-322; TRP-396 AND SER-409.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L13286 mRNA. Translation: AAA62379.1.
AY858838 mRNA. Translation: AAW50795.1.
AL138805 Genomic DNA. Translation: CAB91829.1.
AL138805 Genomic DNA. Translation: CAM27343.1.
BC109083 mRNA. Translation: AAI09084.1.
BC109084 mRNA. Translation: AAI09085.1.
U60669 Genomic DNA. Translation: AAB03776.1. Sequence problems.
S67623 mRNA. Translation: AAB29308.1.
PIRA47436.
I55488.
RefSeqNP_000773.2. NM_000782.4.
NP_001122387.1. NM_001128915.1.
XP_005260361.1. XM_005260304.2.
UniGeneHs.89663.

3D structure databases

ProteinModelPortalQ07973.
SMRQ07973. Positions 51-514.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107963. 2 interactions.
IntActQ07973. 1 interaction.
MINTMINT-6773699.
STRING9606.ENSP00000216862.

Chemistry

BindingDBQ07973.
ChEMBLCHEMBL4521.
DrugBankDB00146. Calcidiol.
DB00136. Calcitriol.
DB00169. Cholecalciferol.
DB00153. Ergocalciferol.
DB00910. Paricalcitol.

PTM databases

PhosphoSiteQ07973.

Polymorphism databases

DMDM19862747.

Proteomic databases

PaxDbQ07973.
PRIDEQ07973.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216862; ENSP00000216862; ENSG00000019186. [Q07973-1]
ENST00000395954; ENSP00000379284; ENSG00000019186. [Q07973-3]
ENST00000395955; ENSP00000379285; ENSG00000019186. [Q07973-2]
GeneID1591.
KEGGhsa:1591.
UCSCuc002xwv.2. human. [Q07973-1]
uc002xww.2. human. [Q07973-2]

Organism-specific databases

CTD1591.
GeneCardsGC20M052769.
HGNCHGNC:2602. CYP24A1.
HPAHPA022261.
MIM126065. gene.
143880. phenotype.
neXtProtNX_Q07973.
Orphanet300547. Autosomal recessive infantile hypercalcemia.
PharmGKBPA27097.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000276540.
HOVERGENHBG099053.
InParanoidQ07973.
KOK07436.
OMAQHDTLAE.
OrthoDBEOG7ZGX4B.
PhylomeDBQ07973.
TreeFamTF105094.

Enzyme and pathway databases

BioCycMetaCyc:HS00395-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
SABIO-RKQ07973.

Gene expression databases

ArrayExpressQ07973.
BgeeQ07973.
CleanExHS_CYP24A1.
GenevestigatorQ07973.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCYP24A1.
GenomeRNAi1591.
NextBio6538.
PROQ07973.
SOURCESearch...

Entry information

Entry nameCP24A_HUMAN
AccessionPrimary (citable) accession number: Q07973
Secondary accession number(s): Q15807, Q32ML3, Q5I2W7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 18, 2001
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM