25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial precursor

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Reviewed, UniProtKB/Swiss-Prot O15528 (CP27B_HUMAN)

Last modified July 7, 2009. Version 90. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
    EC=1.14.13.13
Alternative name(s):
    Cytochrome P450 subfamily XXVIIB polypeptide 1
    Cytochrome p450 27B1
    Calcidiol 1-monooxygenase
    25-OHD-1 alpha-hydroxylase
    25-hydroxyvitamin D(3) 1-alpha-hydroxylase
      Short name=VD3 1A hydroxylase
    P450C1 alpha
    P450VD1-alpha

Gene names

Name:	CYP27B1
Synonyms:	CYP1ALPHA, CYP27B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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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.

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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	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.
Sequence similarities	Belongs to the cytochrome P450 family.

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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
Gene Ontology (GO)
Biological process	G1 to G0 transition Inferred from mutant phenotype. Source: UniProtKB bone mineralization Inferred from expression pattern. Source: UniProtKB calcium ion homeostasis Ref.3 Inferred from mutant phenotype. Source: UniProtKB calcium ion transport Inferred from sequence or structural similarity. Source: UniProtKB decidualization Inferred from expression pattern. Source: UniProtKB negative regulation of calcidiol 1-monooxygenase activity Inferred from direct assay. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell proliferation Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of keratinocyte differentiation Inferred from mutant phenotype. Source: UniProtKB positive regulation of vitamin D receptor signaling pathway Inferred from direct assay. Source: UniProtKB regulation of bone mineralization Ref.3 Inferred from mutant phenotype. Source: UniProtKB response to estrogen stimulus Inferred from expression pattern. Source: UniProtKB response to interferon-gamma Inferred from direct assay. Source: UniProtKB response to lipopolysaccharide Inferred from expression pattern. Source: UniProtKB response to tumor necrosis factor Inferred from expression pattern. Source: UniProtKB response to vitamin D Inferred from expression pattern. Source: UniProtKB vitamin D biosynthetic process Inferred from direct assay. Source: UniProtKB
Cellular component	mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcidiol 1-monooxygenase activity Ref.3 Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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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

Iron (heme axial ligand) By similarity

Natural variations

Natural variant

Q → H in VDDR I. Ref.7

VAR_016969

Natural variant

107

R → H in VDDR I; complete loss of activity. Ref.6

VAR_016952

Natural variant

125

G → E in VDDR I; complete loss of activity. Ref.6

VAR_016953

Natural variant

166

V → L: dbSNP rs8176344. Ref.5

VAR_018841

Natural variant

189

E → G in VDDR I; 22% of wild-type activity. Ref.7 Ref.10

VAR_016954

Natural variant

189

E → K in VDDR I; 11% of wild-type activity. Ref.7 Ref.10

VAR_016967

Natural variant

321

T → R in VDDR I; complete loss of activity. Ref.9

VAR_016955

Natural variant

323

S → Y in VDDR I. Ref.8

VAR_016970

Natural variant

335

R → P in VDDR I; complete loss of activity. Ref.6

VAR_016956

Natural variant

343

L → F in VDDR I; 2.3% of wild-type activity. Ref.10

VAR_016957

Natural variant

382

P → S in VDDR I; complete loss of activity. Ref.6

VAR_016958

Natural variant

389

R → C in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9

VAR_016968

Natural variant

389

R → G in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9

VAR_016960

Natural variant

389

R → H in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9

VAR_016959

Natural variant

409

T → I in VDDR I. Ref.7 Ref.10

VAR_016961

Natural variant

429

R → P in VDDR I. Ref.7

VAR_016971

Natural variant

453

R → C in VDDR I. Ref.7

VAR_016972

Natural variant

478

V → G in VDDR I. Ref.8

VAR_016973

Natural variant

497

P → R in VDDR I. Ref.7

VAR_016974

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Sequences

Sequence

Length

Mass (Da)

Tools

O15528-1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 7F0611EFAD1B5C1C
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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

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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: 9428799] [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: 9344864] [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: 9415400] [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: 9486994] [Abstract] Cited for: VARIANTS VDDR I 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: 9837822] [Abstract] Cited for: VARIANTS VDDR I 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: 10320521] [Abstract] Cited for: VARIANTS VDDR I 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: 10566658] [Abstract] Cited for: VARIANTS VDDR I 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: 12050193] [Abstract] Cited for: VARIANTS VDDR I GLY-189; PHE-343; GLY-389; HIS-389 AND ILE-409.
+	Additional computationally mapped references.

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Web resources

GeneReviews

NIEHS-SNPs

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Cross-references

Sequence databases
	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.
UniGene	Hs.524528
3D structure databases
HSSP	HSSP built from PDB template 1JPZ based on UniProtKB P14779.
ModBase	Search...
Proteomic databases
PRIDE	O15528.
Genome annotation databases
Ensembl	ENSG00000111012. Homo sapiens. [Contig view]
GeneID	1594.
KEGG	hsa:1594.
UCSC	uc001spz.1. human.
Organism-specific databases
GeneCards	GC12M056442.
H-InvDB	HIX0036659.
HGNC	HGNC:2606. CYP27B1.
MIM	264700. phenotype. 609506. gene.
Orphanet	437. Vitamin D resistant rickets.
PharmGKB	PA27099.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O15528.
HOVERGEN	O15528.
OMA	O15528. PNSFRPA.
Enzyme and pathway databases
BRENDA	1.14.13.13. 247.
Reactome	REACT_13433. Biological oxidations. REACT_15314. Hormone biosynthesis.
Gene expression databases
ArrayExpress	O15528.
Bgee	O15528.
CleanEx	HS_CYP27B1.
GermOnline	ENSG00000111012. 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. DB00153. Ergocalciferol.
NextBio	6552.
SOURCE	Search...

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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:	July 7, 2009
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 12

Human chromosome 12: 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Sites

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents