Q07973 (CP24A_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 104.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 514 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence 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 | |
| Involvement in disease | Defects in CYP24A1 are the cause of hypercalcemia infantile (HCAI) [MIM:143880]. HCAI is a disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis. Ref.6 |
| Sequence similarities | Belongs to the cytochrome P450 family. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Mitochondrion |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Domain | Transit peptide |
| Ligand | Heme Iron Metal-binding NADP |
| Molecular function | Monooxygenase Oxidoreductase |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | osteoblast differentiation Inferred from expression pattern. Source: BHF-UCL vitamin D catabolic processNon-traceable author statement. Source: BHF-UCL vitamin D receptor signaling pathwayInferred from expression pattern. Source: BHF-UCL xenobiotic metabolic processTraceable author statement. Source: Reactome |
| Cellular component | mitochondrial inner membrane Traceable author statement. Source: Reactome |
| Molecular function | 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity Inferred from direct assay Ref.1. Source: UniProtKB electron carrier activityInferred from electronic annotation. Source: InterPro heme bindingTraceable author statement Ref.1. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 35 | 35 | Mitochondrion By similarity | ||||||
| Chain | 36 – 514 | 479 | 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial | PRO_0000003615 | |||||
Sites | |||||||||
| Metal binding | 462 | 1 | Iron (heme axial ligand) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 143 | 1 | Missing in HCAI; complete loss of function. | VAR_066408 | |||||
| Natural variant | 157 | 1 | R → Q. Corresponds to variant rs35051736 [ dbSNP | Ensembl ]. | VAR_048464 | |||||
| Natural variant | 159 | 1 | R → Q in HCAI; complete loss of function. Ref.6 | VAR_066409 | |||||
| Natural variant | 322 | 1 | E → K in HCAI; complete loss of function. Ref.6 | VAR_066410 | |||||
| Natural variant | 374 | 1 | M → T. Corresponds to variant rs6022990 [ dbSNP | Ensembl ]. | VAR_048465 | |||||
| Natural variant | 396 | 1 | R → W in HCAI; complete loss of function. Ref.6 | VAR_066411 | |||||
| Natural variant | 409 | 1 | L → S in HCAI; retains small but measurable levels of activity. Ref.6 Corresponds to variant rs6068812 [ dbSNP | Ensembl ]. | VAR_048466 | |||||
Experimental info | |||||||||
| Sequence conflict | 68 | 1 | G → A in AAA62379. Ref.1 | ||||||
| Sequence conflict | 68 | 1 | G → A in AAB03776. Ref.1 | ||||||
| Sequence conflict | 124 – 125 | 2 | AY → V in AAA62379. Ref.1 | ||||||
| Sequence conflict | 270 | 1 | D → G in AAA62379. Ref.1 | ||||||
| Sequence conflict | 365 | 1 | V → R in AAA62379. Ref.1 | ||||||
| Sequence conflict | 368 | 1 | A → E in AAA62379. Ref.1 | ||||||
| Sequence conflict | 390 | 1 | S → G in AAA62379. Ref.1 | ||||||
| Sequence conflict | 511 | 1 | F → S in AAB29308. Ref.4 | ||||||
Sequences
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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: 8506296] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "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. Rogers J.Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "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: 7632726] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104. |
| [4] | "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: 8266831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 258-514. |
| [5] | "Metabolism of vitamin D3 by cytochromes P450." Sakaki T., Kagawa N., Yamamoto K., Inouye K. Front. Biosci. 10:119-134(2005) [PubMed: 15574355] [Abstract] Cited for: SUBSTRATE SPECIFICITY. |
| [6] | "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: 21675912] [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. AL138805 Genomic DNA. Translation: CAB91829.1. U60669 Genomic DNA. Translation: AAB03776.1. Sequence problems. S67623 mRNA. Translation: AAB29308.1. |
| IPI | IPI00020586. |
| PIR | A47436. I55488. |
| RefSeq | NP_000773.2. NM_000782.4. |
| UniGene | Hs.89663. |
3D structure databases | |
| ProteinModelPortal | Q07973. |
| SMR | Q07973. Positions 51-514. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q07973. |
PTM databases | |
| PhosphoSite | Q07973. |
Polymorphism databases | |
| DMDM | 19862747. |
Proteomic databases | |
| PRIDE | Q07973. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000216862; ENSP00000216862; ENSG00000019186. |
| GeneID | 1591. |
| KEGG | hsa:1591. |
| UCSC | uc002xwv.2. human. |
Organism-specific databases | |
| CTD | 1591. |
| GeneCards | GC20M052769. |
| HGNC | HGNC:2602. CYP24A1. |
| HPA | HPA022261. |
| MIM | 126065. gene. 143880. phenotype. |
| neXtProt | NX_Q07973. |
| PharmGKB | PA27097. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG09369. |
| GeneTree | ENSGT00550000074304. |
| HOGENOM | HBG443701. |
| HOVERGEN | HBG099053. |
| InParanoid | Q07973. |
| OMA | EYHKKYG. |
| OrthoDB | EOG4PC9RZ. |
| PhylomeDB | Q07973. |
Enzyme and pathway databases | |
| Reactome | REACT_111217. Metabolism. REACT_15493. Steroid hormones. REACT_22258. Metabolism of lipids and lipoproteins. |
Gene expression databases | |
| ArrayExpress | Q07973. |
| Bgee | Q07973. |
| CleanEx | HS_CYP24A1. |
| Genevestigator | Q07973. |
| GermOnline | ENSG00000019186. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view] |
| Gene3D | G3DSA:1.10.630.10. Cyt_P450. 1 hit. |
| KO | K07436. |
| Pfam | PF00067. p450. 1 hit. [Graphical view] |
| PRINTS | PR00463. EP450I. PR00385. P450. |
| SUPFAM | SSF48264. Cytochrome_P450. 1 hit. |
| PROSITE | PS00086. CYTOCHROME_P450. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| DrugBank | DB00146. Calcidiol. DB00136. Calcitriol. DB00169. Cholecalciferol. DB00153. Ergocalciferol. DB00910. Paricalcitol. |
| NextBio | 6538. |
| SOURCE | Search... |
Entry information
| Entry name | CP24A_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q07973 Secondary accession number(s): Q15807 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 20 Human chromosome 20: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with