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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

    GO - Biological processi

    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

    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.

    Chemistry

    DrugBankiDB00169. Cholecalciferol.
    DB00153. Ergocalciferol.

    Polymorphism and mutation databases

    BioMutaiCYP2R1.
    DMDMi62286619.

    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.
    GenevisibleiQ6VVX0. HS.

    Organism-specific databases

    HPAiHPA042949.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    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.

    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...

    Chemistry

    DrugBankiDB00169. Cholecalciferol.
    DB00153. Ergocalciferol.

    Polymorphism and mutation databases

    BioMutaiCYP2R1.
    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.
    GenevisibleiQ6VVX0. 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...

    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(2003) [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(2004) [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 (OCT-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(2008) [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 (FEB-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(2004) [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: June 24, 2015
    This is version 111 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.