Q07973 (CP24A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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.7
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing 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 PubMed 17023519. Source: BHF-UCL vitamin D catabolic process Non-traceable author statement PubMed 16720713. Source: BHF-UCL vitamin D receptor signaling pathway Inferred from expression pattern PubMed 17426122. 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 25-hydroxycholecalciferol-24-hydroxylase activity Inferred from electronic annotation. Source: Compara electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Traceable author statement Ref.1. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 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.

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
	Alternative sequence	413 – 478	66	Missing in isoform 2.		VSP_043101
	Natural variant	143	1	Missing in HCAI; complete loss of function. Ref.7		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.7		VAR_066409
	Natural variant	322	1	E → K in HCAI; complete loss of function. Ref.7		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.7		VAR_066411
	Natural variant	409	1	L → S in HCAI; retains small but measurable levels of activity. Ref.7 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.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 18, 2001. Version 2. Checksum: 8862F63771981195	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
	Isoform 2 [UniParc]. Checksum: 7A4DF62B195B6F9B	FASTA	448	51,207
	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 KGIVRKYDIQ 430 440 ATDNEPVEML HSGTLVPSRE LPIAFCQR

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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. , 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].
[3]	"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).
[4]	"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.
[5]	"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).
[6]	"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.
[7]	"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. 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.
IPI	IPI00020586. IPI00656023.
PIR	A47436. I55488.
RefSeq	NP_000773.2. NM_000782.4. NP_001122387.1. NM_001128915.1.
UniGene	Hs.89663.
3D structure databases
ProteinModelPortal	Q07973.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000216862.
PTM databases
PhosphoSite	Q07973.
Polymorphism databases
DMDM	19862747.
Proteomic databases
PaxDb	Q07973.
PRIDE	Q07973.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216862; ENSP00000216862; ENSG00000019186. ENST00000395955; ENSP00000379285; 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.
Orphanet	300547. Autosomal recessive infantile hypercalcemia.
PharmGKB	PA27097.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000276540.
HOVERGEN	HBG099053.
InParanoid	Q07973.
KO	K07436.
OMA	EILWKGG.
OrthoDB	EOG4PC9RZ.
PhylomeDB	Q07973.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones.
SABIO-RK	Q07973.
Gene expression databases
ArrayExpress	Q07973.
Bgee	Q07973.
CleanEx	HS_CYP24A1.
Genevestigator	Q07973.
GermOnline	ENSG00000019186. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
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
BindingDB	Q07973.
ChEMBL	CHEMBL4521.
DrugBank	DB00146. Calcidiol. DB00136. Calcitriol. DB00169. Cholecalciferol. DB00153. Ergocalciferol. DB00910. Paricalcitol.
GenomeRNAi	1591.
NextBio	6538.
SOURCE	Search...

Entry information

Entry name

CP24A_HUMAN

Accession

Primary (citable) accession number: Q07973
Secondary accession number(s): Q15807, Q32ML3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 18, 2001
Last modified:	May 1, 2013
This is version 116 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.