Reviewed, UniProtKB/Swiss-Prot Q07973 (CP24A_HUMAN)

Names and origin

Protein names

Recommended name:
    1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
      Short name=Vitamin D(3) 24-hydroxylase
      Short name=24-OHase
    EC=1.14.13.n4
Alternative name(s):
    Cytochrome P450 24A1
    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 transcript 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.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Gene Ontology (GO)
Biological process	osteoblast differentiation Inferred from expression pattern. Source: UniProtKB oxidation reduction Ref.1 Ref.3 Inferred from direct assay. Source: UniProtKB vitamin D catabolic process Non-traceable author statement. Source: UniProtKB vitamin D receptor signaling pathway Non-traceable author statement. Source: UniProtKB
Cellular component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity Ref.1 Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Ref.1 Traceable author statement. Source: UniProtKB oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH as one donor, and incorporation of one atom of oxygen Inferred from electronic annotation. Source: EC
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	157	1	R → Q: dbSNP rs35051736.		VAR_048464
	Natural variant	374	1	M → T: dbSNP rs6022990.		VAR_048465
	Natural variant	409	1	L → S: dbSNP rs6068812.		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

	Sequence		Length	Mass (Da)
	Q07973-1 [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

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. , 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: 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.89663
3D structure databases
HSSP	HSSP built from PDB template 1JPZ based on UniProtKB P14779.
ModBase	Search...
PTM databases
PhosphoSite	Q07973.
Proteomic databases
PRIDE	Q07973.
Genome annotation databases
Ensembl	ENSG00000019186. Homo sapiens. [Contig view]
GeneID	1591.
KEGG	hsa:1591.
Organism-specific databases
GeneCards	GC20M052203.
HGNC	HGNC:2602. CYP24A1.
MIM	126065. gene.
PharmGKB	PA27097.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q07973.
HOVERGEN	Q07973.
OMA	Q07973. RFGLLQK.
Enzyme and pathway databases
Reactome	REACT_13433. Biological oxidations. REACT_13523. Vitamin D (calciferol) metabolism.
Gene expression databases
ArrayExpress	Q07973.
Bgee	Q07973.
CleanEx	HS_CYP24A1.
GermOnline	ENSG00000019186. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHER	PTHR19383. Cyt_P450. 1 hit.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	June 16, 2009
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)