EC 1.14.13.13
Cytochrome P450 subfamily XXVIIB polypeptide 1
Cytochrome p450 27B1
Calcidiol 1-monooxygenase
25-OHD-1 alpha-hydroxylase
25-hydroxyvitamin D(3) 1-alpha-hydroxylase
VD3 1A hydroxylase
P450C1 alpha
P450VD1-alpha

Gene name

	Name:	CYP27B1
	Synonyms:	CYP1ALPHA, CYP27B

From

Homo sapiens (Human)

[TaxID: 9606]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1089/dna.1997.16.1499; PubMed=9428799 [NCBI, ExPASy, EBI, Israel, Japan] Fu G.K., Portale A.P., Miller W.L.; "Complete structure of the human gene for the vitamin D 1alpha-hydroxylase, P450c1alpha."; DNA Cell Biol. 16:1499-1507(1997).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. TISSUE=Kidney; DOI=10.1006/bbrc.1997.7508; PubMed=9344864 [NCBI, ExPASy, EBI, Israel, Japan] Monkawa T., Yoshida T., Wakino S., Shinki T., Anazawa H., Deluca H.F., Suda T., Hayashi M., Saruta T.; "Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1 alpha-hydroxylase."; Biochem. Biophys. Res. Commun. 239:527-533(1997).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1210/me.11.13.1961; PubMed=9415400 [NCBI, ExPASy, EBI, Israel, Japan] Fu G.K., Lin D., Zhang Y.H., Bikle D.D., Shackleton C.H., Miller W.L., Portale A.A.; "Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1."; Mol. Endocrinol. 11:1961-1970(1997).
[4]	NUCLEOTIDE SEQUENCE [MRNA]. Huang D.C., Papavasiliou J., Rhim J., Kremer R.; "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."; Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-166. NIEHS SNPs program; Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
[6]	VARIANTS VDDR I HIS-107; GLU-125; PRO-335 AND SER-382. DOI=10.1056/NEJM199803053381004; PubMed=9486994 [NCBI, ExPASy, EBI, Israel, Japan] Kitanaka S., Takeyama K., Murayama A., Sato T., Okumura K., Nogami M., Hasegawa Y., Niimi H., Yanagisawa J., Tanaka T., Kato S.; "Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets."; N. Engl. J. Med. 338:653-661(1998).
[7]	VARIANTS VDDR I HIS-65; LYS-189; HIS-389; ILE-409; PRO-429; CYS-453 AND ARG-497. DOI=10.1086/302156; PubMed=9837822 [NCBI, ExPASy, EBI, Israel, Japan] Wang J.T., Lin C.-J., Burridge S.M., Fu G.K., Labuda M., Portale A.A., Miller W.L.; "Genetics of vitamin D 1-alpha-hydroxylase deficiency in 17 families."; Am. J. Hum. Genet. 63:1694-1702(1998).
[8]	VARIANTS VDDR I TYR-323 AND GLY-478. DOI=10.1359/jbmr.1999.14.5.730; PubMed=10320521 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "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."; J. Bone Miner. Res. 14:730-739(1999).
[9]	VARIANTS VDDR I ARG-321 AND CYS-389. DOI=10.1210/jc.84.11.4111; PubMed=10566658 [NCBI, ExPASy, EBI, Israel, Japan] Kitanaka S., Murayama A., Sakaki T., Inouye K., Seino Y., Fukumoto S., Shima M., Yukizane S., Takayanagi M., Niimi H., Takeyama K., Kato S.; "No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation."; J. Clin. Endocrinol. Metab. 84:4111-4117(1999).
[10]	VARIANTS VDDR I GLY-189; PHE-343; GLY-389; HIS-389 AND ILE-409. DOI=10.1210/jc.87.6.2424; PubMed=12050193 [NCBI, ExPASy, EBI, Israel, Japan] Wang X., Zhang M.Y., Miller W.L., Portale A.A.; "Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer partial enzyme activity in vitro."; J. Clin. Endocrinol. Metab. 87:2424-2430(2002).

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.
DISEASE: Defects in CYP27B1 are a cause of vitamin D-dependent rickets type 1 (VDDR-1) [MIM:264700]; also known as pseudovitamin D deficiency rickets (PDDR). VDDR-1 is an autosomal recessive disease characterized by muscle weakness and early onset of rickets with hypocalcemia.
SIMILARITY: Belongs to the cytochrome P450 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CYP27B1";.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cyp27b1/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF027152; AAC51854.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB005038; BAA23416.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB005989; BAA22656.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB005990; BAA22657.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006987; BAA23418.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF020192; AAC51853.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF246895; AAF64299.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY288916; AAP31972.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00007313; -.

JC5713; JC5713.

NP_000776.1; -.

3D structure databases

HSSP

P14779; 1JPZ. [HSSP ENTRY / PDB]

ModBase

O15528.

Enzyme and pathway databases

BRENDA

1.14.13.13; 247.

Reactome

REACT_13433; Biological oxidations.
REACT_13523; Vitamin D (calciferol) metabolism.

Organism-specific databases

GC12M056442; -.

HIX0036659; -.

HGNC:2606; CYP27B1.

264700; phenotype. [NCBI / EBI]
609506; gene. [NCBI / EBI]

Orphanet

437; Vitamin D resistant rickets.

PharmGKB

PA27099; -.

Gene expression databases

O15528; -.

O15528; -.

HS_CYP27B1; -.

ENSG00000111012; Homo sapiens.

Ontologies

GO:0031966;	Cellular component: mitochondrial membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0004498;	Molecular function: calcidiol 1-monooxygenase activity (inferred from direct assay from UniProtKB).
GO:0009055;	Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0020037;	Molecular function: heme binding (inferred from electronic annotation from InterPro).
GO:0030282;	Biological process: bone mineralization (inferred from expression pattern from UniProtKB).
GO:0055074;	Biological process: calcium ion homeostasis (inferred from mutant phenotype from UniProtKB).
GO:0006816;	Biological process: calcium ion transport (inferred from sequence or structural similarity from UniProtKB).
GO:0046697;	Biological process: decidualization (inferred from expression pattern from UniProtKB).
GO:0070314;	Biological process: G1 to G0 transition (inferred from mutant phenotype from UniProtKB).
GO:0030308;	Biological process: negative regulation of cell growth (inferred from mutant phenotype from UniProtKB).
GO:0008285;	Biological process: negative regulation of cell proliferation (inferred from direct assay from UniProtKB).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0045618;	Biological process: positive regulation of keratinocyte differentiation (inferred from mutant phenotype from UniProtKB).
GO:0070564;	Biological process: positive regulation of vitamin D receptor signaling pathway (inferred from direct assay from UniProtKB).
GO:0030500;	Biological process: regulation of bone mineralization (inferred from mutant phenotype from UniProtKB).
GO:0043627;	Biological process: response to estrogen stimulus (inferred from expression pattern from UniProtKB).
GO:0034341;	Biological process: response to interferon-gamma (inferred from direct assay from UniProtKB).
GO:0032496;	Biological process: response to lipopolysaccharide (inferred from expression pattern from UniProtKB).
GO:0034612;	Biological process: response to tumor necrosis factor (inferred from expression pattern from UniProtKB).
GO:0033280;	Biological process: response to vitamin D (inferred from expression pattern from UniProtKB).
GO:0042368;	Biological process: vitamin D biosynthetic process (inferred from direct assay from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR001128; Cyt_P450.
IPR017973; Cyt_P450_C.
IPR017972; Cyt_P450_CS.
IPR002401; Cyt_P450_E_grp-I.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.630.10; Cyt_P450; 1.

PANTHER

PTHR19383; Cyt_P450; 1.

Pfam

PF00067; p450; 1.
Pfam graphical view of domain structure.

PRINTS

PR00463; EP450I.
PR00385; P450.

PROSITE

PS00086; CYTOCHROME_P450; 1.

Proteomic databases

PRIDE

O15528; -.

Genome annotation databases

Ensembl

ENSG00000111012; Homo sapiens. [Contig view]

GeneID

1594; -.

KEGG

hsa:1594; -.

Phylogenomic databases

HOGENOM

O15528; -.

HOVERGEN

O15528; -.

OMA

O15528; PNSFRPA.

Other

DrugBank

DB00146; Calcidiol.
DB00136; Calcitriol.
DB00153; Ergocalciferol.

NextBio

6552; -.

SOURCE

CYP27B1; Homo sapiens.

ProtoNet

O15528.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Disease mutation; Heme; Iron; Membrane; Metal-binding; Mitochondrion; Monooxygenase; NADP; Oxidoreductase; Polymorphism; Transit peptide.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`TRANSIT`	`1 ?`		`Mitochondrion (Potential).`
`CHAIN`	`? 508`		`25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial.`	`PRO_0000003622`
`METAL`	`455 455`		`Iron (heme axial ligand) (By similarity).`
`VARIANT`	`65 65`	`1`	`Q -> H (in VDDR I).`	`VAR_016969`
`VARIANT`	`107 107`	`1`	`R -> H (in VDDR I; complete loss of activity).`	`VAR_016952`
`VARIANT`	`125 125`	`1`	`G -> E (in VDDR I; complete loss of activity).`	`VAR_016953`
`VARIANT`	`166 166`	`1`	`V -> L (in dbSNP:rs8176344 [NCBI]).`	`VAR_018841`
`VARIANT`	`189 189`	`1`	`E -> G (in VDDR I; 22% of wild-type activity).`	`VAR_016954`
`VARIANT`	`189 189`	`1`	`E -> K (in VDDR I; 11% of wild-type activity).`	`VAR_016967`
`VARIANT`	`321 321`	`1`	`T -> R (in VDDR I; complete loss of activity).`	`VAR_016955`
`VARIANT`	`323 323`	`1`	`S -> Y (in VDDR I).`	`VAR_016970`
`VARIANT`	`335 335`	`1`	`R -> P (in VDDR I; complete loss of activity).`	`VAR_016956`
`VARIANT`	`343 343`	`1`	`L -> F (in VDDR I; 2.3% of wild-type activity).`	`VAR_016957`
`VARIANT`	`382 382`	`1`	`P -> S (in VDDR I; complete loss of activity).`	`VAR_016958`
`VARIANT`	`389 389`	`1`	`R -> C (in VDDR I; complete loss of activity).`	`VAR_016968`
`VARIANT`	`389 389`	`1`	`R -> G (in VDDR I; complete loss of activity).`	`VAR_016960`
`VARIANT`	`389 389`	`1`	`R -> H (in VDDR I; complete loss of activity).`	`VAR_016959`
`VARIANT`	`409 409`	`1`	`T -> I (in VDDR I).`	`VAR_016961`
`VARIANT`	`429 429`	`1`	`R -> P (in VDDR I).`	`VAR_016971`
`VARIANT`	`453 453`	`1`	`R -> C (in VDDR I).`	`VAR_016972`
`VARIANT`	`478 478`	`1`	`V -> G (in VDDR I).`	`VAR_016973`
`VARIANT`	`497 497`	`1`	`P -> R (in VDDR I).`	`VAR_016974`

Sequence information

Length: 508 AA [This is the length of the unprocessed precursor]

Molecular weight: 56504 Da [This is the MW of the unprocessed precursor]

CRC64: 7F0611EFAD1B5C1C [This is a checksum on the sequence]

        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

O15528 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools