O15528 (CP27B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
EC=1.14.13.13

Alternative name(s):
25-OHD-1 alpha-hydroxylase
25-hydroxyvitamin D(3) 1-alpha-hydroxylase
Short name=VD3 1A hydroxylase
Calcidiol 1-monooxygenase
Cytochrome P450 subfamily XXVIIB polypeptide 1
Cytochrome P450C1 alpha
Cytochrome P450VD1-alpha
Cytochrome p450 27B1

Gene names

Name:	CYP27B1
Synonyms:	CYP1ALPHA, CYP27B

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	508 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	Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.
Catalytic activity	Calcidiol + NADPH + O2 = calcitriol + NADP+ + H2O.
Cofactor	Heme group By similarity.
Pathway	Hormone biosynthesis; cholecalciferol biosynthesis.
Subcellular location	Mitochondrion membrane.
Tissue specificity	Kidney.
Involvement in disease	Rickets vitamin D-dependent 1A (VDDR1A) [MIM:264700]: A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Membrane 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	G1 to G0 transition Inferred from mutant phenotype PubMed 12496369. Source: BHF-UCL bone mineralization Inferred from expression pattern PubMed 17023519. Source: BHF-UCL calcium ion homeostasis Inferred from mutant phenotype Ref.3. Source: BHF-UCL calcium ion transport Inferred from sequence or structural similarity. Source: BHF-UCL decidualization Inferred from expression pattern PubMed 16720713. Source: BHF-UCL negative regulation of calcidiol 1-monooxygenase activity Inferred from direct assay PubMed 16549446PubMed 17426122. Source: BHF-UCL negative regulation of cell growth Inferred from mutant phenotype PubMed 12496369. Source: BHF-UCL negative regulation of cell proliferation Inferred from direct assay PubMed 16549446. Source: BHF-UCL positive regulation of keratinocyte differentiation Inferred from mutant phenotype PubMed 12496369. Source: BHF-UCL positive regulation of vitamin D 24-hydroxylase activity Inferred from direct assay PubMed 16549446. Source: BHF-UCL positive regulation of vitamin D receptor signaling pathway Inferred from direct assay PubMed 16549446. Source: BHF-UCL regulation of bone mineralization Inferred from mutant phenotype Ref.3. Source: BHF-UCL response to estrogen stimulus Inferred from expression pattern PubMed 15795327. Source: BHF-UCL response to interferon-gamma Inferred from direct assay PubMed 9282826. Source: BHF-UCL response to lipopolysaccharide Inferred from expression pattern PubMed 12855575. Source: BHF-UCL response to tumor necrosis factor Inferred from expression pattern PubMed 1690216. Source: BHF-UCL response to vitamin D Inferred from expression pattern PubMed 16549446PubMed 17426122. Source: BHF-UCL vitamin D biosynthetic process Inferred from direct assay PubMed 16549446. Source: BHF-UCL vitamin D catabolic process Inferred from electronic annotation. Source: Compara xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial outer membrane Traceable author statement. Source: Reactome
Molecular_function	calcidiol 1-monooxygenase activity Inferred from direct assay PubMed 15795327PubMed 16549446PubMed 17023519Ref.3. Source: BHF-UCL electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 508		25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial		PRO_0000003622
Sites
	Metal binding	455	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	65	1	Q → H in VDDR1A. Ref.7		VAR_016969
	Natural variant	107	1	R → H in VDDR1A; complete loss of activity. Ref.6 Corresponds to variant rs28934604 [ dbSNP | Ensembl ].		VAR_016952
	Natural variant	125	1	G → E in VDDR1A; complete loss of activity. Ref.6 Corresponds to variant rs28934605 [ dbSNP | Ensembl ].		VAR_016953
	Natural variant	166	1	V → L. Ref.5 Corresponds to variant rs8176344 [ dbSNP | Ensembl ].		VAR_018841
	Natural variant	189	1	E → G in VDDR1A; 22% of wild-type activity. Ref.10		VAR_016954
	Natural variant	189	1	E → K in VDDR1A; 11% of wild-type activity. Ref.7		VAR_016967
	Natural variant	321	1	T → R in VDDR1A; complete loss of activity. Ref.9		VAR_016955
	Natural variant	323	1	S → Y in VDDR1A. Ref.8		VAR_016970
	Natural variant	335	1	R → P in VDDR1A; complete loss of activity. Ref.6 Corresponds to variant rs28934606 [ dbSNP | Ensembl ].		VAR_016956
	Natural variant	343	1	L → F in VDDR1A; 2.3% of wild-type activity. Ref.10		VAR_016957
	Natural variant	382	1	P → S in VDDR1A; complete loss of activity. Ref.6 Corresponds to variant rs28934607 [ dbSNP | Ensembl ].		VAR_016958
	Natural variant	389	1	R → C in VDDR1A; complete loss of activity. Ref.9		VAR_016968
	Natural variant	389	1	R → G in VDDR1A; complete loss of activity. Ref.10		VAR_016960
	Natural variant	389	1	R → H in VDDR1A; complete loss of activity. Ref.7 Ref.10		VAR_016959
	Natural variant	409	1	T → I in VDDR1A. Ref.7 Ref.10		VAR_016961
	Natural variant	429	1	R → P in VDDR1A. Ref.7		VAR_016971
	Natural variant	453	1	R → C in VDDR1A. Ref.7		VAR_016972
	Natural variant	478	1	V → G in VDDR1A. Ref.8		VAR_016973
	Natural variant	497	1	P → R in VDDR1A. Ref.7		VAR_016974

Sequences

	Sequence		Length	Mass (Da)
	O15528 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 7F0611EFAD1B5C1C	FASTA	508	56,504
	10 20 30 40 50 60 MTQTLKYASR VFHRVRWAPE LGASLGYREY HSARRSLADI PGPSTPSFLA ELFCKGGLSR 70 80 90 100 110 120 LHELQVQGAA HFGPVWLASF GTVRTVYVAA PALVEELLRQ EGPRPERCSF SPWTEHRRCR 130 140 150 160 170 180 QRACGLLTAE GEEWQRLRSL LAPLLLRPQA AARYAGTLNN VVCDLVRRLR RQRGRGTGPP 190 200 210 220 230 240 ALVRDVAGEF YKFGLEGIAA VLLGSRLGCL EAQVPPDTET FIRAVGSVFV STLLTMAMPH 250 260 270 280 290 300 WLRHLVPGPW GRLCRDWDQM FAFAQRHVER REAEAAMRNG GQPEKDLESG AHLTHFLFRE 310 320 330 340 350 360 ELPAQSILGN VTELLLAGVD TVSNTLSWAL YELSRHPEVQ TALHSEITAA LSPGSSAYPS 370 380 390 400 410 420 ATVLSQLPLL KAVVKEVLRL YPVVPGNSRV PDKDIHVGDY IIPKNTLVTL CHYATSRDPA 430 440 450 460 470 480 QFPEPNSFRP ARWLGEGPTP HPFASLPFGF GKRSCMGRRL AELELQMALA QILTHFEVQP 490 500 EPGAAPVRPK TRTVLVPERS INLQFLDR

References

[1]	"Complete structure of the human gene for the vitamin D 1alpha-hydroxylase, P450c1alpha." Fu G.K., Portale A.P., Miller W.L. DNA Cell Biol. 16:1499-1507(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1 alpha-hydroxylase." Monkawa T., Yoshida T., Wakino S., Shinki T., Anazawa H., Deluca H.F., Suda T., Hayashi M., Saruta T. Biochem. Biophys. Res. Commun. 239:527-533(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Kidney.
[3]	"Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1." Fu G.K., Lin D., Zhang Y.H., Bikle D.D., Shackleton C.H., Miller W.L., Portale A.A. Mol. Endocrinol. 11:1961-1970(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Targeted disruption of the 25-hydroxyvitamin D3 1 a-hydroxylase gene in a Ras-transformed human keratinocyte cell line: evidence for an autocrine growth regulatory function of 1 alpha, 25-dihydroxyvitamin D3 in vitro and in vivo." Huang D.C., Papavasiliou J., Rhim J., Kremer R. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	NIEHS SNPs program Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-166.
[6]	"Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets." Kitanaka S., Takeyama K., Murayama A., Sato T., Okumura K., Nogami M., Hasegawa Y., Niimi H., Yanagisawa J., Tanaka T., Kato S. N. Engl. J. Med. 338:653-661(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VDDR1A HIS-107; GLU-125; PRO-335 AND SER-382.
[7]	"Genetics of vitamin D 1-alpha-hydroxylase deficiency in 17 families." Wang J.T., Lin C.-J., Burridge S.M., Fu G.K., Labuda M., Portale A.A., Miller W.L. Am. J. Hum. Genet. 63:1694-1702(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VDDR1A HIS-65; LYS-189; HIS-389; ILE-409; PRO-429; CYS-453 AND ARG-497.
[8]	"Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages." Smith S.J., Rucka A.K., Berry J.L., Davies M., Mylchreest S., Paterson C.R., Heath D.A., Tassabehji M., Read A.P., Mee A.P., Mawer E.B. J. Bone Miner. Res. 14:730-739(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VDDR1A TYR-323 AND GLY-478.
[9]	"No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation." Kitanaka S., Murayama A., Sakaki T., Inouye K., Seino Y., Fukumoto S., Shima M., Yukizane S., Takayanagi M., Niimi H., Takeyama K., Kato S. J. Clin. Endocrinol. Metab. 84:4111-4117(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VDDR1A ARG-321 AND CYS-389.
[10]	"Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer partial enzyme activity in vitro." Wang X., Zhang M.Y., Miller W.L., Portale A.A. J. Clin. Endocrinol. Metab. 87:2424-2430(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VDDR1A GLY-189; PHE-343; GLY-389; HIS-389 AND ILE-409.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF027152 Genomic DNA. Translation: AAC51854.1. AB005038 mRNA. Translation: BAA23416.1. AB005989 mRNA. Translation: BAA22656.1. AB005990 Genomic DNA. Translation: BAA22657.1. AB006987 Genomic DNA. Translation: BAA23418.1. AF020192 mRNA. Translation: AAC51853.1. AF246895 mRNA. Translation: AAF64299.1. AY288916 Genomic DNA. Translation: AAP31972.1.
IPI	IPI00007313.
PIR	JC5713.
RefSeq	NP_000776.1. NM_000785.3.
UniGene	Hs.524528.
3D structure databases
ProteinModelPortal	O15528.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000228606.
PTM databases
PhosphoSite	O15528.
Proteomic databases
PaxDb	O15528.
PRIDE	O15528.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000228606; ENSP00000228606; ENSG00000111012.
GeneID	1594.
KEGG	hsa:1594.
UCSC	uc001spz.1. human.
Organism-specific databases
CTD	1594.
GeneCards	GC12M058156.
H-InvDB	HIX0171662.
HGNC	HGNC:2606. CYP27B1.
MIM	264700. phenotype. 609506. gene.
neXtProt	NX_O15528.
Orphanet	289157. Hypocalcemic vitamin D dependent rickets.
PharmGKB	PA27099.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000253961.
HOVERGEN	HBG106909.
InParanoid	O15528.
KO	K07438.
OMA	PWTEHRR.
OrthoDB	EOG4NS3BB.
PhylomeDB	O15528.
Enzyme and pathway databases
BRENDA	1.14.13.13. 2681.
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones.
UniPathway	UPA00955.
Gene expression databases
ArrayExpress	O15528.
Bgee	O15528.
CleanEx	HS_CYP27B1.
Genevestigator	O15528.
GermOnline	ENSG00000111012. 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	O15528.
ChEMBL	CHEMBL5993.
DrugBank	DB00146. Calcidiol. DB00136. Calcitriol. DB00153. Ergocalciferol.
GenomeRNAi	1594.
NextBio	6552.
SOURCE	Search...

Entry information

Entry name

CP27B_HUMAN

Accession

Primary (citable) accession number: O15528

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 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.