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Protein

Vitamin D 25-hydroxylase

Gene

CYP2R1

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

Functioni

Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D2 and D3.3 Publications

Catalytic activityi

Calciol + O2 + NADPH = calcidiol + NADP+ H2O.3 Publications

Cofactori

hemeBy similarity

Kineticsi

  1. KM=0.67 µM for vitamin D22 Publications
  2. KM=0.45 µM for vitamin D32 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei250 – 2501Substrate; via carbonyl oxygen
Metal bindingi448 – 4481Iron (heme axial ligand)

GO - Molecular functioni

  1. heme binding Source: GO_Central
  2. iron ion binding Source: InterPro
  3. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: GO_Central
  4. oxygen binding Source: GO_Central
  5. steroid hydroxylase activity Source: GO_Central
  6. vitamin D3 25-hydroxylase activity Source: Ensembl

GO - Biological processi

  1. exogenous drug catabolic process Source: GO_Central
  2. organic acid metabolic process Source: GO_Central
  3. oxidation-reduction process Source: GO_Central
  4. small molecule metabolic process Source: Reactome
  5. steroid metabolic process Source: Reactome
  6. vitamin D metabolic process Source: Reactome
  7. vitamin metabolic process Source: Reactome
  8. xenobiotic metabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS17721-MONOMER.
BRENDAi1.14.13.159. 2681.
ReactomeiREACT_13450. Vitamins.
REACT_13523. Vitamin D (calciferol) metabolism.
REACT_268491. Defective CYP2R1 causes Rickets vitamin D-dependent 1B (VDDR1B).
SABIO-RKQ6VVX0.

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin D 25-hydroxylase (EC:1.14.13.159)
Alternative name(s):
Cytochrome P450 2R1
Gene namesi
Name:CYP2R1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:20580. CYP2R1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. endoplasmic reticulum membrane Source: Reactome
  3. intracellular membrane-bounded organelle Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Rickets vitamin D-dependent 1B (VDDR1B)1 Publication

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. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activity and low levels of 25-hydroxyvitamin D.

See also OMIM:600081
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti99 – 991L → P in VDDR1B; complete loss of activity. 1 Publication
Corresponds to variant rs61495246 [ dbSNP | Ensembl ].
VAR_021534

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi600081. phenotype.
Orphaneti289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBiPA134986407.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 501501Vitamin D 25-hydroxylasePRO_0000051778Add
BLAST

Proteomic databases

MaxQBiQ6VVX0.
PaxDbiQ6VVX0.
PRIDEiQ6VVX0.

Expressioni

Gene expression databases

BgeeiQ6VVX0.
CleanExiHS_CYP2R1.
ExpressionAtlasiQ6VVX0. baseline and differential.
GenevestigatoriQ6VVX0.

Organism-specific databases

HPAiHPA042949.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000334592.

Structurei

Secondary structure

1
501
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni47 – 493Combined sources
Helixi52 – 576Combined sources
Helixi62 – 7312Combined sources
Beta strandi75 – 817Combined sources
Beta strandi84 – 918Combined sources
Helixi92 – 998Combined sources
Turni100 – 1067Combined sources
Helixi113 – 1197Combined sources
Helixi131 – 14616Combined sources
Turni147 – 1504Combined sources
Helixi154 – 17017Combined sources
Turni171 – 1744Combined sources
Helixi180 – 19617Combined sources
Helixi205 – 22016Combined sources
Helixi224 – 2318Combined sources
Helixi233 – 2375Combined sources
Beta strandi239 – 2413Combined sources
Helixi242 – 26524Combined sources
Helixi276 – 28611Combined sources
Turni287 – 2893Combined sources
Helixi297 – 32832Combined sources
Helixi330 – 34314Combined sources
Beta strandi346 – 3483Combined sources
Helixi352 – 3576Combined sources
Helixi359 – 37214Combined sources
Beta strandi387 – 3893Combined sources
Beta strandi392 – 3943Combined sources
Beta strandi399 – 4035Combined sources
Helixi404 – 4085Combined sources
Turni411 – 4133Combined sources
Beta strandi414 – 4163Combined sources
Helixi422 – 4254Combined sources
Helixi451 – 46818Combined sources
Beta strandi469 – 4724Combined sources
Helixi474 – 4763Combined sources
Beta strandi485 – 4884Combined sources
Beta strandi496 – 5005Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C6GX-ray2.80A/B32-501[»]
3CZHX-ray2.30A/B32-501[»]
3DL9X-ray2.72A/B32-501[»]
ProteinModelPortaliQ6VVX0.
SMRiQ6VVX0. Positions 49-501.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6VVX0.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118775.
HOGENOMiHOG000036991.
HOVERGENiHBG015789.
InParanoidiQ6VVX0.
KOiK07419.
OMAiIMGPNGK.
PhylomeDBiQ6VVX0.
TreeFamiTF352043.

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.

Q6VVX0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWKLWRAEEG AAALGGALFL LLFALGVRQL LKQRRPMGFP PGPPGLPFIG
60 70 80 90 100
NIYSLAASSE LPHVYMRKQS QVYGEIFSLD LGGISTVVLN GYDVVKECLV
110 120 130 140 150
HQSEIFADRP CLPLFMKMTK MGGLLNSRYG RGWVDHRRLA VNSFRYFGYG
160 170 180 190 200
QKSFESKILE ETKFFNDAIE TYKGRPFDFK QLITNAVSNI TNLIIFGERF
210 220 230 240 250
TYEDTDFQHM IELFSENVEL AASASVFLYN AFPWIGILPF GKHQQLFRNA
260 270 280 290 300
AVVYDFLSRL IEKASVNRKP QLPQHFVDAY LDEMDQGKND PSSTFSKENL
310 320 330 340 350
IFSVGELIIA GTETTTNVLR WAILFMALYP NIQGQVQKEI DLIMGPNGKP
360 370 380 390 400
SWDDKCKMPY TEAVLHEVLR FCNIVPLGIF HATSEDAVVR GYSIPKGTTV
410 420 430 440 450
ITNLYSVHFD EKYWRDPEVF HPERFLDSSG YFAKKEALVP FSLGRRHCLG
460 470 480 490 500
EHLARMEMFL FFTALLQRFH LHFPHELVPD LKPRLGMTLQ PQPYLICAER

R
Length:501
Mass (Da):57,359
Last modified:July 5, 2004 - v1
Checksum:iF05E5245C580C29E
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti99 – 991L → P in VDDR1B; complete loss of activity. 1 Publication
Corresponds to variant rs61495246 [ dbSNP | Ensembl ].
VAR_021534

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY323817 mRNA. Translation: AAQ23114.1.
BC104907 mRNA. Translation: AAI04908.1.
BC104909 mRNA. Translation: AAI04910.1.
AY800276 Genomic DNA. Translation: AAV65814.1.
CCDSiCCDS7818.1.
RefSeqiNP_078790.2. NM_024514.4.
UniGeneiHs.371427.

Genome annotation databases

EnsembliENST00000334636; ENSP00000334592; ENSG00000186104.
GeneIDi120227.
KEGGihsa:120227.
UCSCiuc001mlp.3. human.

Polymorphism databases

DMDMi62286619.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY323817 mRNA. Translation: AAQ23114.1.
BC104907 mRNA. Translation: AAI04908.1.
BC104909 mRNA. Translation: AAI04910.1.
AY800276 Genomic DNA. Translation: AAV65814.1.
CCDSiCCDS7818.1.
RefSeqiNP_078790.2. NM_024514.4.
UniGeneiHs.371427.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C6GX-ray2.80A/B32-501[»]
3CZHX-ray2.30A/B32-501[»]
3DL9X-ray2.72A/B32-501[»]
ProteinModelPortaliQ6VVX0.
SMRiQ6VVX0. Positions 49-501.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000334592.

Chemistry

DrugBankiDB00169. Cholecalciferol.
DB00153. Ergocalciferol.

Polymorphism databases

DMDMi62286619.

Proteomic databases

MaxQBiQ6VVX0.
PaxDbiQ6VVX0.
PRIDEiQ6VVX0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000334636; ENSP00000334592; ENSG00000186104.
GeneIDi120227.
KEGGihsa:120227.
UCSCiuc001mlp.3. human.

Organism-specific databases

CTDi120227.
GeneCardsiGC11M014856.
HGNCiHGNC:20580. CYP2R1.
HPAiHPA042949.
MIMi600081. phenotype.
608713. gene.
neXtProtiNX_Q6VVX0.
Orphaneti289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBiPA134986407.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118775.
HOGENOMiHOG000036991.
HOVERGENiHBG015789.
InParanoidiQ6VVX0.
KOiK07419.
OMAiIMGPNGK.
PhylomeDBiQ6VVX0.
TreeFamiTF352043.

Enzyme and pathway databases

BioCyciMetaCyc:HS17721-MONOMER.
BRENDAi1.14.13.159. 2681.
ReactomeiREACT_13450. Vitamins.
REACT_13523. Vitamin D (calciferol) metabolism.
REACT_268491. Defective CYP2R1 causes Rickets vitamin D-dependent 1B (VDDR1B).
SABIO-RKQ6VVX0.

Miscellaneous databases

EvolutionaryTraceiQ6VVX0.
GeneWikiiCYP2R1.
GenomeRNAii120227.
NextBioi80549.
PROiQ6VVX0.
SOURCEiSearch...

Gene expression databases

BgeeiQ6VVX0.
CleanExiHS_CYP2R1.
ExpressionAtlasiQ6VVX0. baseline and differential.
GenevestigatoriQ6VVX0.

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...

Publicationsi

« Hide 'large scale' publications
  1. "De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxylase."
    Cheng J.B., Motola D.L., Mangelsdorf D.J., Russell D.W.
    J. Biol. Chem. 278:38084-38093(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
  3. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.
  4. "Human CYP2R1 gene 5'-flanking region."
    Tsuruga E., Bell N.H., Reddy S.V.
    Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
  5. "Structural analysis of CYP2R1 in complex with vitamin D3."
    Strushkevich N., Usanov S.A., Plotnikov A.N., Jones G., Park H.-W.
    J. Mol. Biol. 380:95-106(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 32-501 IN COMPLEX WITH VITAMIN D3 AND HEME, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
  6. "Crystal structure of CYP2R1 in complexes with 1-alpha-hydroxy-vitamin D2 and with vitamin D2."
    Structural genomics consortium (SGC)
    Submitted (JAN-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.72 ANGSTROMS) OF 32-501 IN COMPLEXES WITH HEME; VITAMIN D2 AND 1-ALPHA-HYDROXY-VITAMIN D2.
  7. "Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase."
    Cheng J.B., Levine M.A., Bell N.H., Mangelsdorf D.J., Russell D.W.
    Proc. Natl. Acad. Sci. U.S.A. 101:7711-7715(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VDDR1B PRO-99.

Entry informationi

Entry nameiCP2R1_HUMAN
AccessioniPrimary (citable) accession number: Q6VVX0
Secondary accession number(s): Q2M3H3, Q5RT65
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: July 5, 2004
Last modified: April 1, 2015
This is version 108 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.