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O15528 (CP27B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.10 Ref.11 Ref.12 Ref.13 Ref.14

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1 to G0 transition

Inferred from mutant phenotype Ref.4. Source: BHF-UCL

bone mineralization

Inferred from expression pattern PubMed 17023519. Source: BHF-UCL

calcitriol biosynthetic process from calciol

Inferred from direct assay PubMed 15795327PubMed 16549446PubMed 17023519Ref.3. Source: BHF-UCL

calcium ion homeostasis

Inferred from mutant phenotype Ref.3. Source: BHF-UCL

calcium ion transport

Inferred from electronic annotation. Source: Ensembl

decidualization

Inferred from expression pattern PubMed 16720713. Source: BHF-UCL

negative regulation of calcidiol 1-monooxygenase activity

Inferred from direct assay PubMed 16549446. Source: BHF-UCL

negative regulation of cell growth

Inferred from mutant phenotype Ref.4. 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 Ref.4. 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

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 direct assay PubMed 12855575. Source: BHF-UCL

response to vitamin D

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement. Source: Reactome

vitamin D catabolic process

Inferred from electronic annotation. Source: Ensembl

vitamin D metabolic process

Inferred from direct assay Ref.3. Source: BHF-UCL

vitamin metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15589699PubMed 16720713. Source: BHF-UCL

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncalcidiol 1-monooxygenase activity

Inferred from electronic annotation. Source: Ensembl

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-KW

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 50825-hydroxyvitamin D-1 alpha hydroxylase, mitochondrialPRO_0000003622

Sites

Metal binding4551Iron (heme axial ligand) By similarity

Natural variations

Natural variant651Q → H in VDDR1A. Ref.11
VAR_016969
Natural variant1071R → H in VDDR1A; complete loss of activity. Ref.10
Corresponds to variant rs28934604 [ dbSNP | Ensembl ].
VAR_016952
Natural variant1251G → E in VDDR1A; complete loss of activity. Ref.10
Corresponds to variant rs28934605 [ dbSNP | Ensembl ].
VAR_016953
Natural variant1661V → L. Ref.6
Corresponds to variant rs8176344 [ dbSNP | Ensembl ].
VAR_018841
Natural variant1891E → G in VDDR1A; 22% of wild-type activity. Ref.14
VAR_016954
Natural variant1891E → K in VDDR1A; 11% of wild-type activity. Ref.11
VAR_016967
Natural variant3211T → R in VDDR1A; complete loss of activity. Ref.13
VAR_016955
Natural variant3231S → Y in VDDR1A. Ref.12
VAR_016970
Natural variant3351R → P in VDDR1A; complete loss of activity. Ref.10
Corresponds to variant rs28934606 [ dbSNP | Ensembl ].
VAR_016956
Natural variant3431L → F in VDDR1A; 2.3% of wild-type activity. Ref.14
VAR_016957
Natural variant3821P → S in VDDR1A; complete loss of activity. Ref.10
Corresponds to variant rs28934607 [ dbSNP | Ensembl ].
VAR_016958
Natural variant3891R → C in VDDR1A; complete loss of activity. Ref.13
VAR_016968
Natural variant3891R → G in VDDR1A; complete loss of activity. Ref.14
VAR_016960
Natural variant3891R → H in VDDR1A; complete loss of activity. Ref.11 Ref.14
VAR_016959
Natural variant4091T → I in VDDR1A. Ref.11 Ref.14
VAR_016961
Natural variant4291R → P in VDDR1A. Ref.11
VAR_016971
Natural variant4531R → C in VDDR1A. Ref.11
VAR_016972
Natural variant4781V → G in VDDR1A. Ref.12
VAR_016973
Natural variant4971P → R in VDDR1A. Ref.11
VAR_016974

Experimental info

Sequence conflict3201D → N in BAG37458. Ref.7

Sequences

Sequence LengthMass (Da)Tools
O15528 [UniParc].

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

FASTA50856,504
        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 

« Hide

References

« Hide 'large scale' 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 1alpha-hydroxylase gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in an autocrine fashion."
Huang D.C., Papavasiliou V., Rhim J.S., Horst R.L., Kremer R.
Mol. Cancer Res. 1:56-67(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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].
[6]NIEHS SNPs program
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-166.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[8]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.

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.
AF256213 Genomic DNA. Translation: AAG00416.1.
AF246895 mRNA. Translation: AAF64299.1.
AY288916 Genomic DNA. Translation: AAP31972.1.
AK314953 mRNA. Translation: BAG37458.1.
CH471054 Genomic DNA. Translation: EAW97067.1.
BC136386 mRNA. Translation: AAI36387.1.
PIRJC5713.
RefSeqNP_000776.1. NM_000785.3.
UniGeneHs.524528.

3D structure databases

ProteinModelPortalO15528.
SMRO15528. Positions 35-505.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000228606.

Chemistry

BindingDBO15528.
ChEMBLCHEMBL5993.
DrugBankDB00146. Calcidiol.
DB00136. Calcitriol.
DB00153. Ergocalciferol.

PTM databases

PhosphoSiteO15528.

Proteomic databases

PaxDbO15528.
PRIDEO15528.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228606; ENSP00000228606; ENSG00000111012.
GeneID1594.
KEGGhsa:1594.
UCSCuc001spz.1. human.

Organism-specific databases

CTD1594.
GeneCardsGC12M058156.
H-InvDBHIX0171662.
HGNCHGNC:2606. CYP27B1.
HPAHPA043358.
MIM264700. phenotype.
609506. gene.
neXtProtNX_O15528.
Orphanet289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBPA27099.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000253961.
HOVERGENHBG106909.
InParanoidO15528.
KOK07438.
OMALHSEITA.
OrthoDBEOG7ZGX4B.
PhylomeDBO15528.
TreeFamTF105094.

Enzyme and pathway databases

BRENDA1.14.13.13. 2681.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
UniPathwayUPA00955.

Gene expression databases

ArrayExpressO15528.
BgeeO15528.
CleanExHS_CYP27B1.
GenevestigatorO15528.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWiki25-Hydroxyvitamin_D3_1-alpha-hydroxylase.
GenomeRNAi1594.
NextBio35468145.
PROO15528.
SOURCESearch...

Entry information

Entry nameCP27B_HUMAN
AccessionPrimary (citable) accession number: O15528
Secondary accession number(s): B2RC61, Q548T3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM