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Q6VVX0

- CP2R1_HUMAN

UniProt

Q6VVX0 - CP2R1_HUMAN

Protein

Vitamin D 25-hydroxylase

Gene

CYP2R1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    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

    Heme group.By 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: InterPro
    2. iron ion binding Source: InterPro
    3. monooxygenase activity Source: UniProtKB-KW
    4. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Source: InterPro
    5. vitamin D3 25-hydroxylase activity Source: Ensembl

    GO - Biological processi

    1. response to cesium ion Source: Ensembl
    2. response to ionizing radiation Source: Ensembl
    3. small molecule metabolic process Source: Reactome
    4. steroid metabolic process Source: Reactome
    5. vitamin D metabolic process Source: Reactome
    6. vitamin metabolic process Source: Reactome
    7. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS17721-MONOMER.
    ReactomeiREACT_13450. Vitamins.
    REACT_13523. Vitamin D (calciferol) metabolism.
    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: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:20580. CYP2R1.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Involvement in diseasei

    Rickets vitamin D-dependent 1B (VDDR1B) [MIM:600081]: 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. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activity and low levels of 25-hydroxyvitamin D.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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

    ArrayExpressiQ6VVX0.
    BgeeiQ6VVX0.
    CleanExiHS_CYP2R1.
    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 – 493
    Helixi52 – 576
    Helixi62 – 7312
    Beta strandi75 – 817
    Beta strandi84 – 918
    Helixi92 – 998
    Turni100 – 1067
    Helixi113 – 1197
    Helixi131 – 14616
    Turni147 – 1504
    Helixi154 – 17017
    Turni171 – 1744
    Helixi180 – 19617
    Helixi205 – 22016
    Helixi224 – 2318
    Helixi233 – 2375
    Beta strandi239 – 2413
    Helixi242 – 26524
    Helixi276 – 28611
    Turni287 – 2893
    Helixi297 – 32832
    Helixi330 – 34314
    Beta strandi346 – 3483
    Helixi352 – 3576
    Helixi359 – 37214
    Beta strandi387 – 3893
    Beta strandi392 – 3943
    Beta strandi399 – 4035
    Helixi404 – 4085
    Turni411 – 4133
    Beta strandi414 – 4163
    Helixi422 – 4254
    Helixi451 – 46818
    Beta strandi469 – 4724
    Helixi474 – 4763
    Beta strandi485 – 4884
    Beta strandi496 – 5005

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MWKLWRAEEG AAALGGALFL LLFALGVRQL LKQRRPMGFP PGPPGLPFIG    50
    NIYSLAASSE LPHVYMRKQS QVYGEIFSLD LGGISTVVLN GYDVVKECLV 100
    HQSEIFADRP CLPLFMKMTK MGGLLNSRYG RGWVDHRRLA VNSFRYFGYG 150
    QKSFESKILE ETKFFNDAIE TYKGRPFDFK QLITNAVSNI TNLIIFGERF 200
    TYEDTDFQHM IELFSENVEL AASASVFLYN AFPWIGILPF GKHQQLFRNA 250
    AVVYDFLSRL IEKASVNRKP QLPQHFVDAY LDEMDQGKND PSSTFSKENL 300
    IFSVGELIIA GTETTTNVLR WAILFMALYP NIQGQVQKEI DLIMGPNGKP 350
    SWDDKCKMPY TEAVLHEVLR FCNIVPLGIF HATSEDAVVR GYSIPKGTTV 400
    ITNLYSVHFD EKYWRDPEVF HPERFLDSSG YFAKKEALVP FSLGRRHCLG 450
    EHLARMEMFL FFTALLQRFH LHFPHELVPD LKPRLGMTLQ PQPYLICAER 500
    R 501
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY323817 mRNA. Translation: AAQ23114.1 .
    BC104907 mRNA. Translation: AAI04908.1 .
    BC104909 mRNA. Translation: AAI04910.1 .
    AY800276 Genomic DNA. Translation: AAV65814.1 .
    CCDSi CCDS7818.1.
    RefSeqi NP_078790.2. NM_024514.4.
    UniGenei Hs.371427.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3C6G X-ray 2.80 A/B 32-501 [» ]
    3CZH X-ray 2.30 A/B 32-501 [» ]
    3DL9 X-ray 2.72 A/B 32-501 [» ]
    ProteinModelPortali Q6VVX0.
    SMRi Q6VVX0. Positions 49-501.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000334592.

    Chemistry

    DrugBanki DB00169. Cholecalciferol.
    DB00153. Ergocalciferol.

    Polymorphism databases

    DMDMi 62286619.

    Proteomic databases

    MaxQBi Q6VVX0.
    PaxDbi Q6VVX0.
    PRIDEi Q6VVX0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000334636 ; ENSP00000334592 ; ENSG00000186104 .
    GeneIDi 120227.
    KEGGi hsa:120227.
    UCSCi uc001mlp.3. human.

    Organism-specific databases

    CTDi 120227.
    GeneCardsi GC11M014856.
    HGNCi HGNC:20580. CYP2R1.
    HPAi HPA042949.
    MIMi 600081. phenotype.
    608713. gene.
    neXtProti NX_Q6VVX0.
    Orphaneti 289157. Hypocalcemic vitamin D-dependent rickets.
    PharmGKBi PA134986407.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000036991.
    HOVERGENi HBG015789.
    InParanoidi Q6VVX0.
    KOi K07419.
    OMAi IMGPNGK.
    PhylomeDBi Q6VVX0.
    TreeFami TF352043.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS17721-MONOMER.
    Reactomei REACT_13450. Vitamins.
    REACT_13523. Vitamin D (calciferol) metabolism.
    SABIO-RK Q6VVX0.

    Miscellaneous databases

    EvolutionaryTracei Q6VVX0.
    GeneWikii CYP2R1.
    GenomeRNAii 120227.
    NextBioi 80549.
    PROi Q6VVX0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q6VVX0.
    Bgeei Q6VVX0.
    CleanExi HS_CYP2R1.
    Genevestigatori Q6VVX0.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 103 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