CP2R1_MOUSE
ID CP2R1_MOUSE Reviewed; 501 AA.
AC Q6VVW9;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Vitamin D 25-hydroxylase;
DE EC=1.14.14.24 {ECO:0000269|PubMed:12867411};
DE AltName: Full=Cytochrome P450 2R1;
GN Name=Cyp2r1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6Jx129SvEv;
RX PubMed=12867411; DOI=10.1074/jbc.m307028200;
RA Cheng J.B., Motola D.L., Mangelsdorf D.J., Russell D.W.;
RT "De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-
RT hydroxylase.";
RL J. Biol. Chem. 278:38084-38093(2003).
RN [2]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24019477; DOI=10.1073/pnas.1315006110;
RA Zhu J.G., Ochalek J.T., Kaufmann M., Jones G., Deluca H.F.;
RT "CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D
RT production in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:15650-15655(2013).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in activation of
CC vitamin D precursors (PubMed:12867411, PubMed:24019477). Catalyzes
CC hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3)
CC (calciol). Can metabolize vitamin D analogs/prodrugs 1alpha-
CC hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3)
CC (alfacalcidol) forming 25-hydroxy derivatives. Mechanistically, uses
CC molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein
CC reductase) (PubMed:12867411, PubMed:24019477) (By similarity).
CC {ECO:0000250|UniProtKB:Q6VVX0, ECO:0000269|PubMed:12867411,
CC ECO:0000269|PubMed:24019477}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calciol + O2 + reduced [NADPH--hemoprotein reductase] =
CC calcidiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:32903, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17933, ChEBI:CHEBI:28940, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.24;
CC Evidence={ECO:0000269|PubMed:12867411};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32904;
CC Evidence={ECO:0000305|PubMed:12867411};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + vitamin D2 = 25-
CC hydroxyvitamin D2 + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:46580, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28934, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:86319; Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46581;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1alpha-hydroxyvitamin D2 + O2 + reduced [NADPH--hemoprotein
CC reductase] = 1alpha,25-dihydroxyvitamin D2 + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46584, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:4712,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:86320;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46585;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alfacalcidol + O2 + reduced [NADPH--hemoprotein reductase] =
CC calcitriol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49272, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17823, ChEBI:CHEBI:31186, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49273;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC -!- PATHWAY: Hormone biosynthesis; vitamin D biosynthesis.
CC {ECO:0000250|UniProtKB:Q6VVX0}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6VVX0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6VVX0}; Peripheral membrane protein. Microsome
CC membrane {ECO:0000250|UniProtKB:Q6VVX0}; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in the liver and testis.
CC {ECO:0000269|PubMed:12867411, ECO:0000269|PubMed:24019477}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate and have normal development. They display substantial reduction of
CC serum calcidiol levels. {ECO:0000269|PubMed:24019477}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY323818; AAQ23115.1; -; mRNA.
DR CCDS; CCDS21761.1; -.
DR RefSeq; NP_796356.2; NM_177382.4.
DR AlphaFoldDB; Q6VVW9; -.
DR SMR; Q6VVW9; -.
DR BioGRID; 232622; 8.
DR STRING; 10090.ENSMUSP00000032908; -.
DR iPTMnet; Q6VVW9; -.
DR PhosphoSitePlus; Q6VVW9; -.
DR MaxQB; Q6VVW9; -.
DR PaxDb; Q6VVW9; -.
DR PRIDE; Q6VVW9; -.
DR ProteomicsDB; 283812; -.
DR Antibodypedia; 24708; 223 antibodies from 28 providers.
DR Ensembl; ENSMUST00000032908; ENSMUSP00000032908; ENSMUSG00000030670.
DR GeneID; 244209; -.
DR KEGG; mmu:244209; -.
DR UCSC; uc009jid.2; mouse.
DR CTD; 120227; -.
DR MGI; MGI:2449771; Cyp2r1.
DR VEuPathDB; HostDB:ENSMUSG00000030670; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000158305; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; Q6VVW9; -.
DR OMA; AEINQTG; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q6VVW9; -.
DR TreeFam; TF352043; -.
DR BRENDA; 1.14.14.24; 3474.
DR Reactome; R-MMU-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-MMU-211916; Vitamins.
DR UniPathway; UPA00954; -.
DR BioGRID-ORCS; 244209; 4 hits in 73 CRISPR screens.
DR PRO; PR:Q6VVW9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q6VVW9; protein.
DR Bgee; ENSMUSG00000030670; Expressed in left lobe of liver and 69 other tissues.
DR ExpressionAtlas; Q6VVW9; baseline and differential.
DR Genevisible; Q6VVW9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:1902271; F:D3 vitamins binding; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0030343; F:vitamin D3 25-hydroxylase activity; IDA:MGI.
DR GO; GO:0036378; P:calcitriol biosynthetic process from calciol; ISO:MGI.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0042359; P:vitamin D metabolic process; IDA:MGI.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..501
FT /note="Vitamin D 25-hydroxylase"
FT /id="PRO_0000051779"
FT BINDING 250
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6VVX0"
FT BINDING 448
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q6VVX0"
SQ SEQUENCE 501 AA; 57313 MW; C1A1BAD71E630A98 CRC64;
MLELPGARAC AGALAGALLL LLFVLVVRQL LRQRRPAGFP PGPPRLPFVG NICSLALSAD
LPHVYMRKQS RVYGEIFSLD LGGISTVVLN GYDVVKECLV HQSEIFADRP CLPLFMKMTK
MGGLLNSRYG RGWIDHRRLA VNSFHYFGSG QKSFESKILE ETWSLIDAIE TYKGGPFDLK
QLITNAVSNI TNLILFGERF TYEDTDFQHM IELFSENVEL AASAPVFLYN AFPWIGILPF
GKHQRLFRNA DVVYDFLSRL IEKAAVNRKP HLPHHFVDAY LDEMDQGQND PLSTFSKENL
IFSVGELIIA GTETTTNVLR WAILFMALYP NIQGQVHKEI DLIVGHNRRP SWEYKCKMPY
TEAVLHEVLR FCNIVPLGIF HATSEDAVVR GYSIPKGTTV ITNLYSVHFD EKYWKDPDMF
YPERFLDSNG YFTKKEALIP FSLGRRHCLG EQLARMEMFL FFTSLLQQFH LHFPHELVPN
LKPRLGMTLQ PQPYLICAER R
