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Q6VVX0 (CP2R1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vitamin D 25-hydroxylase

EC=1.14.13.159
Alternative name(s):
Cytochrome P450 2R1
Gene names
Name:CYP2R1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length501 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D2 and D3. Ref.1 Ref.2 Ref.5

Catalytic activity

Calciol + O2 + NADPH = calcidiol + NADP+ H2O. Ref.1 Ref.2 Ref.5

Cofactor

Heme group By similarity.

Subunit structure

Homodimer. Ref.5

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the cytochrome P450 family.

Biophysicochemical properties

Kinetic parameters:

KM=0.67 µM for vitamin D2 Ref.2 Ref.5

KM=0.45 µM for vitamin D3

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 501501Vitamin D 25-hydroxylase
PRO_0000051778

Sites

Metal binding4481Iron (heme axial ligand)
Binding site2501Substrate; via carbonyl oxygen

Natural variations

Natural variant991L → P in VDDR1B; complete loss of activity. Ref.7
Corresponds to variant rs61495246 [ dbSNP | Ensembl ].
VAR_021534

Secondary structure

.................................................................. 501
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q6VVX0 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: F05E5245C580C29E

FASTA50157,359
        10         20         30         40         50         60 
MWKLWRAEEG AAALGGALFL LLFALGVRQL LKQRRPMGFP PGPPGLPFIG NIYSLAASSE 

        70         80         90        100        110        120 
LPHVYMRKQS QVYGEIFSLD LGGISTVVLN GYDVVKECLV HQSEIFADRP CLPLFMKMTK 

       130        140        150        160        170        180 
MGGLLNSRYG RGWVDHRRLA VNSFRYFGYG QKSFESKILE ETKFFNDAIE TYKGRPFDFK 

       190        200        210        220        230        240 
QLITNAVSNI TNLIIFGERF TYEDTDFQHM IELFSENVEL AASASVFLYN AFPWIGILPF 

       250        260        270        280        290        300 
GKHQQLFRNA AVVYDFLSRL IEKASVNRKP QLPQHFVDAY LDEMDQGKND PSSTFSKENL 

       310        320        330        340        350        360 
IFSVGELIIA GTETTTNVLR WAILFMALYP NIQGQVQKEI DLIMGPNGKP SWDDKCKMPY 

       370        380        390        400        410        420 
TEAVLHEVLR FCNIVPLGIF HATSEDAVVR GYSIPKGTTV ITNLYSVHFD EKYWRDPEVF 

       430        440        450        460        470        480 
HPERFLDSSG YFAKKEALVP FSLGRRHCLG EHLARMEMFL FFTALLQRFH LHFPHELVPD 

       490        500 
LKPRLGMTLQ PQPYLICAER R 

« Hide

References

« Hide 'large scale' references
[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]"Metabolism of vitamin D by human microsomal CYP2R1."
Shinkyo R., Sakaki T., Kamakura M., Ohta M., Inouye K.
Biochem. Biophys. Res. Commun. 324:451-457(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY323817 mRNA. Translation: AAQ23114.1.
BC104907 mRNA. Translation: AAI04908.1.
BC104909 mRNA. Translation: AAI04910.1.
AY800276 Genomic DNA. Translation: AAV65814.1.
CCDSCCDS7818.1.
RefSeqNP_078790.2. NM_024514.4.
UniGeneHs.371427.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3C6GX-ray2.80A/B32-501[»]
3CZHX-ray2.30A/B32-501[»]
3DL9X-ray2.72A/B32-501[»]
ProteinModelPortalQ6VVX0.
SMRQ6VVX0. Positions 49-501.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000334592.

Chemistry

DrugBankDB00169. Cholecalciferol.
DB00153. Ergocalciferol.

Polymorphism databases

DMDM62286619.

Proteomic databases

MaxQBQ6VVX0.
PaxDbQ6VVX0.
PRIDEQ6VVX0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334636; ENSP00000334592; ENSG00000186104.
ENST00000572354; ENSP00000461178; ENSG00000262968.
GeneID120227.
KEGGhsa:120227.
UCSCuc001mlp.3. human.

Organism-specific databases

CTD120227.
GeneCardsGC11M014856.
HGNCHGNC:20580. CYP2R1.
HPAHPA042949.
MIM600081. phenotype.
608713. gene.
neXtProtNX_Q6VVX0.
Orphanet289157. Hypocalcemic vitamin D-dependent rickets.
PharmGKBPA134986407.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000036991.
HOVERGENHBG015789.
InParanoidQ6VVX0.
KOK07419.
OMAIMGPNGK.
PhylomeDBQ6VVX0.
TreeFamTF352043.

Enzyme and pathway databases

BioCycMetaCyc:HS17721-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
SABIO-RKQ6VVX0.

Gene expression databases

ArrayExpressQ6VVX0.
BgeeQ6VVX0.
CleanExHS_CYP2R1.
GenevestigatorQ6VVX0.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ6VVX0.
GeneWikiCYP2R1.
GenomeRNAi120227.
NextBio80549.
PROQ6VVX0.
SOURCESearch...

Entry information

Entry nameCP2R1_HUMAN
AccessionPrimary (citable) accession number: Q6VVX0
Secondary accession number(s): Q2M3H3, Q5RT65
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM