Vitamin D 25-hydroxylase
Details
- Name
- Vitamin D 25-hydroxylase
- Kind
- protein
- Synonyms
- 1.14.14.24
- Cytochrome P450 2R1
- Gene Name
- CYP2R1
- UniProtKB Entry
- Q6VVX0Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0018963|Vitamin D 25-hydroxylase MWKLWRAEEGAAALGGALFLLLFALGVRQLLKQRRPMGFPPGPPGLPFIGNIYSLAASSE LPHVYMRKQSQVYGEIFSLDLGGISTVVLNGYDVVKECLVHQSEIFADRPCLPLFMKMTK MGGLLNSRYGRGWVDHRRLAVNSFRYFGYGQKSFESKILEETKFFNDAIETYKGRPFDFK QLITNAVSNITNLIIFGERFTYEDTDFQHMIELFSENVELAASASVFLYNAFPWIGILPF GKHQQLFRNAAVVYDFLSRLIEKASVNRKPQLPQHFVDAYLDEMDQGKNDPSSTFSKENL IFSVGELIIAGTETTTNVLRWAILFMALYPNIQGQVQKEIDLIMGPNGKPSWDDKCKMPY TEAVLHEVLRFCNIVPLGIFHATSEDAVVRGYSIPKGTTVITNLYSVHFDEKYWRDPEVF HPERFLDSSGYFAKKEALVPFSLGRRHCLGEHLARMEMFLFFTALLQRFHLHFPHELVPD LKPRLGMTLQPQPYLICAERR
- Number of residues
- 501
- Molecular Weight
- 57358.82
- Theoretical pI
- 7.67
- GO Classification
- FunctionsD3 vitamins binding / protein homodimerization activityProcessescalcitriol biosynthetic process from calciol
- General Function
- A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol) (PubMed:12867411, PubMed:15465040, PubMed:18511070). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives (PubMed:15465040, PubMed:18511070). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:12867411, PubMed:15465040, PubMed:18511070)
- Specific Function
- D3 vitamins binding
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- 1-26
- Transmembrane Regions
- Not Available
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0018964|Vitamin D 25-hydroxylase (CYP2R1) ATGTGGAAGCTTTGGAGAGCTGAAGAGGGCGCGGCGGCGCTCGGCGGCGCGCTCTTCCTG CTGCTCTTCGCGCTAGGGGTCCGCCAGCTGCTGAAGCAGAGGCGGCCGATGGGCTTCCCC CCGGGGCCGCCGGGGCTGCCATTTATCGGCAACATCTATTCCCTGGCAGCCTCATCCGAG CTTCCCCATGTCTACATGAGAAAGCAGAGCCAGGTGTACGGAGAGATCTTCAGTTTAGAT CTTGGAGGCATATCAACTGTGGTTCTAAATGGCTATGATGTAGTAAAGGAATGCCTTGTT CATCAAAGCGAAATTTTTGCAGACAGACCATGCCTTCCTTTATTCATGAAGATGACAAAA ATGGGAGGCTTACTCAATTCCAGATATGGCCGAGGATGGGTTGATCACAGACGATTAGCT GTAAACAGTTTTCGATATTTTGGATATGGCCAAAAGTCTTTTGAATCTAAAATCTTGGAA GAAACCAAATTTTTCAATGATGCTATTGAAACATACAAAGGTAGACCTTTTGACTTTAAA CAGTTAATAACGAATGCTGTTTCAAACATAACCAATCTGATCATTTTTGGAGAACGATTC ACTTATGAAGACACCGATTTTCAGCACATGATTGAGTTATTTAGTGAAAATGTGGAACTA GCTGCCAGTGCCTCAGTCTTCTTGTATAATGCCTTTCCATGGATTGGCATCCTGCCTTTT GGAAAACATCAACAGCTGTTTAGAAATGCAGCTGTAGTCTATGATTTTCTCTCCAGACTC ATTGAAAAAGCTTCAGTCAACAGAAAGCCTCAGCTACCTCAGCATTTTGTTGATGCTTAT TTAGATGAGATGGATCAAGGTAAAAATGACCCATCATCTACTTTCTCCAAAGAAAACCTA ATTTTCTCAGTGGGTGAACTCATCATTGCTGGAACTGAAACTACAACCAATGTGCTACGG TGGGCGATTCTTTTCATGGCCCTTTATCCTAATATTCAAGGACAAGTTCAGAAAGAGATT GATTTAATTATGGGCCCTAATGGGAAGCCTTCTTGGGACGACAAATGCAAAATGCCTTAT ACTGAGGCAGTTTTGCATGAAGTTTTAAGATTCTGTAATATAGTTCCATTAGGGATTTTC CATGCAACCTCTGAAGATGCAGTTGTACGTGGTTATTCCATTCCTAAAGGCACAACAGTA ATTACAAATCTTTATTCTGTACACTTTGATGAAAAGTACTGGAGAGACCCAGAAGTGTTC CATCCTGAGCGATTTCTGGACAGCAGTGGATATTTTGCCAAGAAGGAAGCTTTGGTTCCT TTTTCCCTAGGAAGAAGACATTGTCTTGGAGAACACTTGGCTCGGATGGAAATGTTCTTG TTTTTTACAGCATTGCTTCAGAGGTTTCATTTGCATTTTCCACATGAACTAGTTCCAGAT CTGAAGCCCAGGTTAGGCATGACATTGCAGCCCCAACCCTACCTCATCTGTGCTGAAAGA CGCTGA
- Chromosome Location
- 11
- Locus
- 11p15.2
- External Identifiers
Resource Link UniProtKB ID Q6VVX0 UniProtKB Entry Name CP2R1_HUMAN GenBank Protein ID 33591222 GenBank Gene ID AY323817 GeneCard ID CYP2R1 GenAtlas ID CYP2R1 HGNC ID HGNC:20580 PDB ID(s) 3C6G, 3CZH, 3DL9 KEGG ID hsa:120227 NCBI Gene ID 120227 - General References
- Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW: De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003 Sep 26;278(39):38084-93. Epub 2003 Jul 16. [Article]
- Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K: Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun. 2004 Nov 5;324(1):451-7. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW: Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008 Jun 27;380(1):95-106. doi: 10.1016/j.jmb.2008.03.065. Epub 2008 Apr 8. [Article]
- Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW: Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5. Epub 2004 May 5. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Ergocalciferol approved, nutraceutical no enzyme substrate Details Cholecalciferol approved, nutraceutical unknown enzyme substrate Details Vitamin D approved, nutraceutical, vet_approved yes enzyme substrate Details