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Q07973

- CP24A_HUMAN

UniProt

Q07973 - CP24A_HUMAN

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Protein
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Gene
CYP24A1, CYP24
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

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

Cofactori

Heme group By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi462 – 4621Iron (heme axial ligand) By similarity

GO - Molecular functioni

  1. 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity Source: UniProtKB
  2. 25-hydroxycholecalciferol-24-hydroxylase activity Source: Ensembl
  3. heme binding Source: UniProtKB
  4. iron ion binding Source: InterPro
  5. oxidoreductase activity Source: UniProtKB

GO - Biological processi

  1. osteoblast differentiation Source: BHF-UCL
  2. oxidation-reduction process Source: UniProtKB
  3. response to vitamin D Source: BHF-UCL
  4. small molecule metabolic process Source: Reactome
  5. steroid metabolic process Source: Reactome
  6. vitamin D catabolic process Source: BHF-UCL
  7. vitamin D metabolic process Source: Reactome
  8. vitamin D receptor signaling pathway Source: BHF-UCL
  9. vitamin metabolic process Source: Reactome
  10. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00395-MONOMER.
ReactomeiREACT_13450. Vitamins.
REACT_13523. Vitamin D (calciferol) metabolism.
SABIO-RKQ07973.

Names & Taxonomyi

Protein namesi
Recommended name:
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (EC:1.14.13.126)
Short name:
24-OHase
Short name:
Vitamin D(3) 24-hydroxylase
Alternative name(s):
Cytochrome P450 24A1
Cytochrome P450-CC24
Gene namesi
Name:CYP24A1
Synonyms:CYP24
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:2602. CYP24A1.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial inner membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431Missing in HCAI; complete loss of function. 1 Publication
VAR_066408
Natural varianti159 – 1591R → Q in HCAI; complete loss of function. 1 Publication
VAR_066409
Natural varianti322 – 3221E → K in HCAI; complete loss of function. 1 Publication
VAR_066410
Natural varianti396 – 3961R → W in HCAI; complete loss of function. 1 Publication
Corresponds to variant rs114368325 [ dbSNP | Ensembl ].
VAR_066411
Natural varianti409 – 4091L → S in HCAI; retains small but measurable levels of activity. 1 Publication
Corresponds to variant rs6068812 [ dbSNP | Ensembl ].
VAR_048466

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi143880. phenotype.
Orphaneti300547. Autosomal recessive infantile hypercalcemia.
PharmGKBiPA27097.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3535Mitochondrion By similarity
Add
BLAST
Chaini36 – 5144791,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
PRO_0000003615Add
BLAST

Proteomic databases

MaxQBiQ07973.
PaxDbiQ07973.
PRIDEiQ07973.

PTM databases

PhosphoSiteiQ07973.

Expressioni

Gene expression databases

ArrayExpressiQ07973.
BgeeiQ07973.
CleanExiHS_CYP24A1.
GenevestigatoriQ07973.

Organism-specific databases

HPAiHPA022261.

Interactioni

Protein-protein interaction databases

BioGridi107963. 2 interactions.
IntActiQ07973. 1 interaction.
MINTiMINT-6773699.
STRINGi9606.ENSP00000216862.

Structurei

3D structure databases

ProteinModelPortaliQ07973.
SMRiQ07973. Positions 51-514.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG2124.
HOGENOMiHOG000276540.
HOVERGENiHBG099053.
InParanoidiQ07973.
KOiK07436.
OMAiQHDTLAE.
OrthoDBiEOG7ZGX4B.
PhylomeDBiQ07973.
TreeFamiTF105094.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q07973-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MSSPISKSRS LAAFLQQLRS PRQPPRLVTS TAYTSPQPRE VPVCPLTAGG    50
ETQNAAALPG PTSWPLLGSL LQILWKGGLK KQHDTLVEYH KKYGKIFRMK 100
LGSFESVHLG SPCLLEALYR TESAYPQRLE IKPWKAYRDY RKEGYGLLIL 150
EGEDWQRVRS AFQKKLMKPG EVMKLDNKIN EVLADFMGRI DELCDERGHV 200
EDLYSELNKW SFESICLVLY EKRFGLLQKN AGDEAVNFIM AIKTMMSTFG 250
RMMVTPVELH KSLNTKVWQD HTLAWDTIFK SVKACIDNRL EKYSQQPSAD 300
FLCDIYHQNR LSKKELYAAV TELQLAAVET TANSLMWILY NLSRNPQVQQ 350
KLLKEIQSVL PENQVPRAED LRNMPYLKAC LKESMRLTPS VPFTTRTLDK 400
ATVLGEYALP KGTVLMLNTQ VLGSSEDNFE DSSQFRPERW LQEKEKINPF 450
AHLPFGVGKR MCIGRRLAEL QLHLALCWIV RKYDIQATDN EPVEMLHSGT 500
LVPSRELPIA FCQR 514
Length:514
Mass (Da):58,875
Last modified:October 18, 2001 - v2
Checksum:i8862F63771981195
GO
Isoform 2 (identifier: Q07973-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     413-478: Missing.

Note: No experimental confirmation available.

Show »
Length:448
Mass (Da):51,207
Checksum:i7A4DF62B195B6F9B
GO
Isoform 3 (identifier: Q07973-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:372
Mass (Da):43,051
Checksum:i943689E132C4FE3B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431Missing in HCAI; complete loss of function. 1 Publication
VAR_066408
Natural varianti157 – 1571R → Q.
Corresponds to variant rs35051736 [ dbSNP | Ensembl ].
VAR_048464
Natural varianti159 – 1591R → Q in HCAI; complete loss of function. 1 Publication
VAR_066409
Natural varianti322 – 3221E → K in HCAI; complete loss of function. 1 Publication
VAR_066410
Natural varianti374 – 3741M → T.
Corresponds to variant rs6022990 [ dbSNP | Ensembl ].
VAR_048465
Natural varianti396 – 3961R → W in HCAI; complete loss of function. 1 Publication
Corresponds to variant rs114368325 [ dbSNP | Ensembl ].
VAR_066411
Natural varianti409 – 4091L → S in HCAI; retains small but measurable levels of activity. 1 Publication
Corresponds to variant rs6068812 [ dbSNP | Ensembl ].
VAR_048466

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 88MSSPISKS → MYSCFSHR in isoform 3.
VSP_053367
Alternative sequencei9 – 150142Missing in isoform 3.
VSP_053368Add
BLAST
Alternative sequencei413 – 47866Missing in isoform 2.
VSP_043101Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681G → A in AAA62379. 1 Publication
Sequence conflicti68 – 681G → A in AAB03776. 1 Publication
Sequence conflicti124 – 1252AY → V in AAA62379. 1 Publication
Sequence conflicti270 – 2701D → G in AAA62379. 1 Publication
Sequence conflicti365 – 3651V → R in AAA62379. 1 Publication
Sequence conflicti368 – 3681A → E in AAA62379. 1 Publication
Sequence conflicti390 – 3901S → G in AAA62379. 1 Publication
Sequence conflicti511 – 5111F → S in AAB29308. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS33491.1. [Q07973-1]
CCDS46616.1. [Q07973-2]
PIRiA47436.
I55488.
RefSeqiNP_000773.2. NM_000782.4. [Q07973-1]
NP_001122387.1. NM_001128915.1. [Q07973-2]
XP_005260361.1. XM_005260304.2. [Q07973-1]
UniGeneiHs.89663.

Genome annotation databases

EnsembliENST00000216862; ENSP00000216862; ENSG00000019186. [Q07973-1]
ENST00000395954; ENSP00000379284; ENSG00000019186. [Q07973-3]
ENST00000395955; ENSP00000379285; ENSG00000019186. [Q07973-2]
GeneIDi1591.
KEGGihsa:1591.
UCSCiuc002xwv.2. human. [Q07973-1]
uc002xww.2. human. [Q07973-2]

Polymorphism databases

DMDMi19862747.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS33491.1. [Q07973-1 ]
CCDS46616.1. [Q07973-2 ]
PIRi A47436.
I55488.
RefSeqi NP_000773.2. NM_000782.4. [Q07973-1 ]
NP_001122387.1. NM_001128915.1. [Q07973-2 ]
XP_005260361.1. XM_005260304.2. [Q07973-1 ]
UniGenei Hs.89663.

3D structure databases

ProteinModelPortali Q07973.
SMRi Q07973. Positions 51-514.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107963. 2 interactions.
IntActi Q07973. 1 interaction.
MINTi MINT-6773699.
STRINGi 9606.ENSP00000216862.

Chemistry

BindingDBi Q07973.
ChEMBLi CHEMBL4521.
DrugBanki DB00146. Calcidiol.
DB00136. Calcitriol.
DB00169. Cholecalciferol.
DB00153. Ergocalciferol.
DB00910. Paricalcitol.

PTM databases

PhosphoSitei Q07973.

Polymorphism databases

DMDMi 19862747.

Proteomic databases

MaxQBi Q07973.
PaxDbi Q07973.
PRIDEi Q07973.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000216862 ; ENSP00000216862 ; ENSG00000019186 . [Q07973-1 ]
ENST00000395954 ; ENSP00000379284 ; ENSG00000019186 . [Q07973-3 ]
ENST00000395955 ; ENSP00000379285 ; ENSG00000019186 . [Q07973-2 ]
GeneIDi 1591.
KEGGi hsa:1591.
UCSCi uc002xwv.2. human. [Q07973-1 ]
uc002xww.2. human. [Q07973-2 ]

Organism-specific databases

CTDi 1591.
GeneCardsi GC20M052769.
HGNCi HGNC:2602. CYP24A1.
HPAi HPA022261.
MIMi 126065. gene.
143880. phenotype.
neXtProti NX_Q07973.
Orphaneti 300547. Autosomal recessive infantile hypercalcemia.
PharmGKBi PA27097.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
HOGENOMi HOG000276540.
HOVERGENi HBG099053.
InParanoidi Q07973.
KOi K07436.
OMAi QHDTLAE.
OrthoDBi EOG7ZGX4B.
PhylomeDBi Q07973.
TreeFami TF105094.

Enzyme and pathway databases

BioCyci MetaCyc:HS00395-MONOMER.
Reactomei REACT_13450. Vitamins.
REACT_13523. Vitamin D (calciferol) metabolism.
SABIO-RK Q07973.

Miscellaneous databases

GeneWikii CYP24A1.
GenomeRNAii 1591.
NextBioi 6538.
PROi Q07973.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q07973.
Bgeei Q07973.
CleanExi HS_CYP24A1.
Genevestigatori Q07973.

Family and domain databases

Gene3Di 1.10.630.10. 1 hit.
InterProi IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiCP24A_HUMAN
AccessioniPrimary (citable) accession number: Q07973
Secondary accession number(s): Q15807, Q32ML3, Q5I2W7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 18, 2001
Last modified: September 3, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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