1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial precursor

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Q07973 (CP24A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 104. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names 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

Name:	CYP24A1
Synonyms:	CYP24

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	Mitochondrion.
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 process Non-traceable author statement. Source: BHF-UCL vitamin D receptor signaling pathway Inferred from expression pattern. Source: BHF-UCL xenobiotic metabolic process Traceable 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 activity Inferred from electronic annotation. Source: InterPro heme binding Traceable 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

Mitochondrion By similarity

Chain

36 – 514

479

1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

PRO_0000003615

Sites

Metal binding

462

Iron (heme axial ligand) Potential

Natural variations

Natural variant

143

Missing in HCAI; complete loss of function.

VAR_066408

Natural variant

157

R → Q.
Corresponds to variant rs35051736 [ dbSNP | Ensembl ].

VAR_048464

Natural variant

159

R → Q in HCAI; complete loss of function. Ref.6

VAR_066409

Natural variant

322

E → K in HCAI; complete loss of function. Ref.6

VAR_066410

Natural variant

374

M → T.
Corresponds to variant rs6022990 [ dbSNP | Ensembl ].

VAR_048465

Natural variant

396

R → W in HCAI; complete loss of function. Ref.6

VAR_066411

Natural variant

409

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

G → A in AAA62379. Ref.1

Sequence conflict

G → A in AAB03776. Ref.1

Sequence conflict

124 – 125

AY → V in AAA62379. Ref.1

Sequence conflict

270

D → G in AAA62379. Ref.1

Sequence conflict

365

V → R in AAA62379. Ref.1

Sequence conflict

368

A → E in AAA62379. Ref.1

Sequence conflict

390

S → G in AAA62379. Ref.1

Sequence conflict

511

F → S in AAB29308. Ref.4

Sequences

Sequence

Length

Mass (Da)

Tools

Q07973 [UniParc].

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

FASTA

514

58,875

        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

References

	« Hide 'large scale' referencesShow '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

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 18, 2001
Last modified:	January 25, 2012
This is version 104 of the entry and version 2 of the sequence. [Complete history]

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

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents