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Protein

25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial

Gene

CYP27B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D3) to 1-alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), and of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) to 1-alpha,24,25-trihydroxyvitamin D3 (1alpha,24,25(OH)3D3). Is also active with 25-hydroxy-24-oxo-vitamin D3. Plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.1 Publication

Catalytic activityi

Calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitriol + 2 oxidized adrenodoxin + H2O.1 Publication
Secalciferol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitetrol + 2 oxidized adrenodoxin + H2O.1 Publication

Cofactori

hemeBy similarity

Kineticsi

  1. KM=2.7 µM for 25-hydroxyvitamin D31 Publication
  2. KM=1.1 µM for 24,25-dihydroxyvitamin D31 Publication
  1. Vmax=3.9 pmol/min/mg enzyme with 25-hydroxyvitamin D3 as substrate1 Publication
  2. Vmax=3.2 pmol/min/mg enzyme with 24,25-dihydroxyvitamin D3 as substrate1 Publication

Pathwayi: cholecalciferol biosynthesis

This protein is involved in the pathway cholecalciferol biosynthesis, which is part of Hormone biosynthesis.
View all proteins of this organism that are known to be involved in the pathway cholecalciferol biosynthesis and in Hormone biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi455Iron (heme axial ligand)By similarity1

GO - Molecular functioni

GO - Biological processi

  • bone mineralization Source: BHF-UCL
  • calcitriol biosynthetic process from calciol Source: BHF-UCL
  • calcium ion homeostasis Source: BHF-UCL
  • calcium ion transport Source: BHF-UCL
  • decidualization Source: BHF-UCL
  • G1 to G0 transition Source: BHF-UCL
  • negative regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • positive regulation of keratinocyte differentiation Source: BHF-UCL
  • positive regulation of vitamin D 24-hydroxylase activity Source: BHF-UCL
  • positive regulation of vitamin D receptor signaling pathway Source: BHF-UCL
  • regulation of bone mineralization Source: BHF-UCL
  • response to estrogen Source: BHF-UCL
  • response to interferon-gamma Source: BHF-UCL
  • response to lipopolysaccharide Source: BHF-UCL
  • response to vitamin D Source: BHF-UCL
  • vitamin D catabolic process Source: Ensembl
  • vitamin D metabolic process Source: BHF-UCL
  • vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciZFISH:HS03361-MONOMER.
BRENDAi1.14.13.13. 2681.
ReactomeiR-HSA-196791. Vitamin D (calciferol) metabolism.
R-HSA-211916. Vitamins.
UniPathwayiUPA00955.

Chemistry databases

SwissLipidsiSLP:000001478.

Names & Taxonomyi

Protein namesi
Recommended name:
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (EC:1.14.15.181 Publication)
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 namesi
Name:CYP27B1
Synonyms:CYP1ALPHA, CYP27B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:2606. CYP27B1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • mitochondrial outer membrane Source: Reactome
  • mitochondrion Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Rickets vitamin D-dependent 1A (VDDR1A)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:264700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01696965Q → H in VDDR1A. 1 Publication1
Natural variantiVAR_016952107R → H in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934604dbSNPEnsembl.1
Natural variantiVAR_016953125G → E in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934605dbSNPEnsembl.1
Natural variantiVAR_016954189E → G in VDDR1A; 22% of wild-type activity. 1 PublicationCorresponds to variant rs118204012dbSNPEnsembl.1
Natural variantiVAR_016967189E → K in VDDR1A; 11% of wild-type activity. 1 Publication1
Natural variantiVAR_016955321T → R in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204007dbSNPEnsembl.1
Natural variantiVAR_016970323S → Y in VDDR1A. 1 Publication1
Natural variantiVAR_016956335R → P in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934606dbSNPEnsembl.1
Natural variantiVAR_016957343L → F in VDDR1A; 2.3% of wild-type activity. 1 PublicationCorresponds to variant rs118204011dbSNPEnsembl.1
Natural variantiVAR_016958382P → S in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934607dbSNPEnsembl.1
Natural variantiVAR_016968389R → C in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204010dbSNPEnsembl.1
Natural variantiVAR_016960389R → G in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204010dbSNPEnsembl.1
Natural variantiVAR_016959389R → H in VDDR1A; complete loss of activity. 2 PublicationsCorresponds to variant rs118204009dbSNPEnsembl.1
Natural variantiVAR_016961409T → I in VDDR1A. 2 PublicationsCorresponds to variant rs118204008dbSNPEnsembl.1
Natural variantiVAR_016971429R → P in VDDR1A. 1 Publication1
Natural variantiVAR_016972453R → C in VDDR1A. 1 PublicationCorresponds to variant rs767480544dbSNPEnsembl.1
Natural variantiVAR_016973478V → G in VDDR1A. 1 Publication1
Natural variantiVAR_016974497P → R in VDDR1A. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1594.
MalaCardsiCYP27B1.
MIMi264700. phenotype.
OpenTargetsiENSG00000111012.
Orphaneti289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBiPA27099.

Chemistry databases

ChEMBLiCHEMBL5993.
DrugBankiDB01436. Alfacalcidol.
DB00146. Calcidiol.
DB01285. Corticotropin.
DB00153. Ergocalciferol.
GuidetoPHARMACOLOGYi1370.

Polymorphism and mutation databases

BioMutaiCYP27B1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000003622? – 50825-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Proteomic databases

PaxDbiO15528.
PeptideAtlasiO15528.
PRIDEiO15528.
TopDownProteomicsiO15528.

PTM databases

PhosphoSitePlusiO15528.

Expressioni

Tissue specificityi

Kidney.

Gene expression databases

BgeeiENSG00000111012.
CleanExiHS_CYP27B1.
ExpressionAtlasiO15528. baseline and differential.
GenevisibleiO15528. HS.

Organism-specific databases

HPAiHPA043358.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000228606.

Chemistry databases

BindingDBiO15528.

Structurei

3D structure databases

ProteinModelPortaliO15528.
SMRiO15528.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0159. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000119243.
HOGENOMiHOG000253961.
HOVERGENiHBG106909.
InParanoidiO15528.
KOiK07438.
OMAiHRQRACG.
OrthoDBiEOG091G0MI3.
PhylomeDBiO15528.
TreeFamiTF105094.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O15528-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTQTLKYASR VFHRVRWAPE LGASLGYREY HSARRSLADI PGPSTPSFLA
60 70 80 90 100
ELFCKGGLSR LHELQVQGAA HFGPVWLASF GTVRTVYVAA PALVEELLRQ
110 120 130 140 150
EGPRPERCSF SPWTEHRRCR QRACGLLTAE GEEWQRLRSL LAPLLLRPQA
160 170 180 190 200
AARYAGTLNN VVCDLVRRLR RQRGRGTGPP ALVRDVAGEF YKFGLEGIAA
210 220 230 240 250
VLLGSRLGCL EAQVPPDTET FIRAVGSVFV STLLTMAMPH WLRHLVPGPW
260 270 280 290 300
GRLCRDWDQM FAFAQRHVER REAEAAMRNG GQPEKDLESG AHLTHFLFRE
310 320 330 340 350
ELPAQSILGN VTELLLAGVD TVSNTLSWAL YELSRHPEVQ TALHSEITAA
360 370 380 390 400
LSPGSSAYPS ATVLSQLPLL KAVVKEVLRL YPVVPGNSRV PDKDIHVGDY
410 420 430 440 450
IIPKNTLVTL CHYATSRDPA QFPEPNSFRP ARWLGEGPTP HPFASLPFGF
460 470 480 490 500
GKRSCMGRRL AELELQMALA QILTHFEVQP EPGAAPVRPK TRTVLVPERS

INLQFLDR
Length:508
Mass (Da):56,504
Last modified:January 1, 1998 - v1
Checksum:i7F0611EFAD1B5C1C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti320D → N in BAG37458 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01696965Q → H in VDDR1A. 1 Publication1
Natural variantiVAR_016952107R → H in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934604dbSNPEnsembl.1
Natural variantiVAR_016953125G → E in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934605dbSNPEnsembl.1
Natural variantiVAR_018841166V → L.1 PublicationCorresponds to variant rs8176344dbSNPEnsembl.1
Natural variantiVAR_016954189E → G in VDDR1A; 22% of wild-type activity. 1 PublicationCorresponds to variant rs118204012dbSNPEnsembl.1
Natural variantiVAR_016967189E → K in VDDR1A; 11% of wild-type activity. 1 Publication1
Natural variantiVAR_016955321T → R in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204007dbSNPEnsembl.1
Natural variantiVAR_016970323S → Y in VDDR1A. 1 Publication1
Natural variantiVAR_016956335R → P in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934606dbSNPEnsembl.1
Natural variantiVAR_016957343L → F in VDDR1A; 2.3% of wild-type activity. 1 PublicationCorresponds to variant rs118204011dbSNPEnsembl.1
Natural variantiVAR_016958382P → S in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs28934607dbSNPEnsembl.1
Natural variantiVAR_016968389R → C in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204010dbSNPEnsembl.1
Natural variantiVAR_016960389R → G in VDDR1A; complete loss of activity. 1 PublicationCorresponds to variant rs118204010dbSNPEnsembl.1
Natural variantiVAR_016959389R → H in VDDR1A; complete loss of activity. 2 PublicationsCorresponds to variant rs118204009dbSNPEnsembl.1
Natural variantiVAR_016961409T → I in VDDR1A. 2 PublicationsCorresponds to variant rs118204008dbSNPEnsembl.1
Natural variantiVAR_016971429R → P in VDDR1A. 1 Publication1
Natural variantiVAR_016972453R → C in VDDR1A. 1 PublicationCorresponds to variant rs767480544dbSNPEnsembl.1
Natural variantiVAR_016973478V → G in VDDR1A. 1 Publication1
Natural variantiVAR_016974497P → R in VDDR1A. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8954.1.
PIRiJC5713.
RefSeqiNP_000776.1. NM_000785.3.
UniGeneiHs.524528.

Genome annotation databases

EnsembliENST00000228606; ENSP00000228606; ENSG00000111012.
GeneIDi1594.
KEGGihsa:1594.
UCSCiuc001spz.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8954.1.
PIRiJC5713.
RefSeqiNP_000776.1. NM_000785.3.
UniGeneiHs.524528.

3D structure databases

ProteinModelPortaliO15528.
SMRiO15528.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000228606.

Chemistry databases

BindingDBiO15528.
ChEMBLiCHEMBL5993.
DrugBankiDB01436. Alfacalcidol.
DB00146. Calcidiol.
DB01285. Corticotropin.
DB00153. Ergocalciferol.
GuidetoPHARMACOLOGYi1370.
SwissLipidsiSLP:000001478.

PTM databases

PhosphoSitePlusiO15528.

Polymorphism and mutation databases

BioMutaiCYP27B1.

Proteomic databases

PaxDbiO15528.
PeptideAtlasiO15528.
PRIDEiO15528.
TopDownProteomicsiO15528.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000228606; ENSP00000228606; ENSG00000111012.
GeneIDi1594.
KEGGihsa:1594.
UCSCiuc001spz.2. human.

Organism-specific databases

CTDi1594.
DisGeNETi1594.
GeneCardsiCYP27B1.
H-InvDBHIX0171662.
HGNCiHGNC:2606. CYP27B1.
HPAiHPA043358.
MalaCardsiCYP27B1.
MIMi264700. phenotype.
609506. gene.
neXtProtiNX_O15528.
OpenTargetsiENSG00000111012.
Orphaneti289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBiPA27099.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0159. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000119243.
HOGENOMiHOG000253961.
HOVERGENiHBG106909.
InParanoidiO15528.
KOiK07438.
OMAiHRQRACG.
OrthoDBiEOG091G0MI3.
PhylomeDBiO15528.
TreeFamiTF105094.

Enzyme and pathway databases

UniPathwayiUPA00955.
BioCyciZFISH:HS03361-MONOMER.
BRENDAi1.14.13.13. 2681.
ReactomeiR-HSA-196791. Vitamin D (calciferol) metabolism.
R-HSA-211916. Vitamins.

Miscellaneous databases

GeneWikii25-Hydroxyvitamin_D3_1-alpha-hydroxylase.
GenomeRNAii1594.
PROiO15528.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111012.
CleanExiHS_CYP27B1.
ExpressionAtlasiO15528. baseline and differential.
GenevisibleiO15528. HS.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCP27B_HUMAN
AccessioniPrimary (citable) accession number: O15528
Secondary accession number(s): B2RC61, Q548T3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.