Reviewed,
UniProtKB/Swiss-Prot O15528 (CP27B_HUMAN)
Last modified
July 7, 2009.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
| ||||
| 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 |
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 | |
| Subcellular location | |
| 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. |
Ontologies
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 VDDR I. Ref.7 | VAR_016969 | |||||
| Natural variant | 107 | 1 | R → H in VDDR I; complete loss of activity. Ref.6 | VAR_016952 | |||||
| Natural variant | 125 | 1 | G → E in VDDR I; complete loss of activity. Ref.6 | VAR_016953 | |||||
| Natural variant | 166 | 1 | V → L: dbSNP rs8176344. Ref.5 | VAR_018841 | |||||
| Natural variant | 189 | 1 | E → G in VDDR I; 22% of wild-type activity. Ref.7 Ref.10 | VAR_016954 | |||||
| Natural variant | 189 | 1 | E → K in VDDR I; 11% of wild-type activity. Ref.7 Ref.10 | VAR_016967 | |||||
| Natural variant | 321 | 1 | T → R in VDDR I; complete loss of activity. Ref.9 | VAR_016955 | |||||
| Natural variant | 323 | 1 | S → Y in VDDR I. Ref.8 | VAR_016970 | |||||
| Natural variant | 335 | 1 | R → P in VDDR I; complete loss of activity. Ref.6 | VAR_016956 | |||||
| Natural variant | 343 | 1 | L → F in VDDR I; 2.3% of wild-type activity. Ref.10 | VAR_016957 | |||||
| Natural variant | 382 | 1 | P → S in VDDR I; complete loss of activity. Ref.6 | VAR_016958 | |||||
| Natural variant | 389 | 1 | R → C in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9 | VAR_016968 | |||||
| Natural variant | 389 | 1 | R → G in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9 | VAR_016960 | |||||
| Natural variant | 389 | 1 | R → H in VDDR I; complete loss of activity. Ref.7 Ref.10 Ref.9 | VAR_016959 | |||||
| Natural variant | 409 | 1 | T → I in VDDR I. Ref.7 Ref.10 | VAR_016961 | |||||
| Natural variant | 429 | 1 | R → P in VDDR I. Ref.7 | VAR_016971 | |||||
| Natural variant | 453 | 1 | R → C in VDDR I. Ref.7 | VAR_016972 | |||||
| Natural variant | 478 | 1 | V → G in VDDR I. Ref.8 | VAR_016973 | |||||
| Natural variant | 497 | 1 | P → R in VDDR I. Ref.7 | VAR_016974 | |||||
Sequences
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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. |
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... |
Entry information
| Entry name | CP27B_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O15528 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


