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Q6VVX0

- CP2R1_HUMAN

UniProt

Q6VVX0 - CP2R1_HUMAN

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Protein

Vitamin D 25-hydroxylase

Gene

CYP2R1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

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. small molecule metabolic process Source: Reactome
  2. steroid metabolic process Source: Reactome
  3. vitamin D metabolic process Source: Reactome
  4. vitamin metabolic process Source: Reactome
  5. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

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
Complete GO annotation...

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

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 – 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.
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 [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:
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.
GeneTreei ENSGT00760000118775.
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

Bgeei Q6VVX0.
CleanExi HS_CYP2R1.
ExpressionAtlasi Q6VVX0. baseline and differential.
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

« 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: October 29, 2014
This is version 104 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