ID VDR_MOUSE Reviewed; 422 AA. AC P48281; Q922X0; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 193. DE RecName: Full=Vitamin D3 receptor; DE Short=VDR; DE AltName: Full=1,25-dihydroxyvitamin D3 receptor; DE AltName: Full=Nuclear receptor subfamily 1 group I member 1; GN Name=Vdr; Synonyms=Nr1i1; 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]. RX PubMed=7835717; DOI=10.1016/0378-1119(94)00735-b; RA Kamei Y., Kawada T., Fukuwatari T., Ono T., Kato S., Sugimoto E.; RT "Cloning and sequencing of the gene encoding the mouse vitamin D RT receptor."; RL Gene 152:281-282(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; TISSUE=Intestine; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION. RX PubMed=12016314; DOI=10.1126/science.1070477; RA Makishima M., Lu T.T., Xie W., Whitfield G.K., Domoto H., Evans R.M., RA Haussler M.R., Mangelsdorf D.J.; RT "Vitamin D receptor as an intestinal bile acid sensor."; RL Science 296:1313-1316(2002). RN [6] RP INDUCTION. RX PubMed=14528024; DOI=10.1210/me.2003-0048; RA Tsujikawa H., Kurotaki Y., Fujimori T., Fukuda K., Nabeshima Y.; RT "Klotho, a gene related to a syndrome resembling human premature aging, RT functions in a negative regulatory circuit of vitamin D endocrine system."; RL Mol. Endocrinol. 17:2393-2403(2003). RN [7] RP INTERACTION WITH CRY1 AND CRY2. RX PubMed=28751364; DOI=10.1073/pnas.1704955114; RA Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E., RA Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T., RA Zhao X., Downes M., Evans R.M., Lamia K.A.; RT "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors RT and modulate transcriptional activity."; RL Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017). RN [8] RP FUNCTION. RX PubMed=32354638; DOI=10.1016/j.kint.2020.01.032; RA Hashimoto N., Matsui I., Ishizuka S., Inoue K., Matsumoto A., Shimada K., RA Hori S., Lee D.G., Yasuda S., Katsuma Y., Kajimoto S., Doi Y., RA Yamaguchi S., Kubota K., Oka T., Sakaguchi Y., Takabatake Y., Hamano T., RA Isaka Y.; RT "Lithocholic acid increases intestinal phosphate and calcium absorption in RT a vitamin D receptor dependent but transcellular pathway independent RT manner."; RL Kidney Int. 97:1164-1180(2020). CC -!- FUNCTION: Nuclear receptor for calcitriol, the active form of vitamin CC D3 which mediates the action of this vitamin on cells (By similarity). CC Enters the nucleus upon vitamin D3 binding where it forms heterodimers CC with the retinoid X receptor/RXR (By similarity). The VDR-RXR CC heterodimers bind to specific response elements on DNA and activate the CC transcription of vitamin D3-responsive target genes (By similarity). CC Plays a central role in calcium homeostasis (PubMed:32354638). Also CC functions as a receptor for the secondary bile acid lithocholic acid CC (LCA) and its metabolites (PubMed:12016314, PubMed:32354638). CC {ECO:0000250|UniProtKB:P11473, ECO:0000250|UniProtKB:P13053, CC ECO:0000269|PubMed:12016314, ECO:0000269|PubMed:32354638}. CC -!- SUBUNIT: Homodimer in the absence of bound vitamin D3. Heterodimer with CC RXRA after vitamin D3 binding. Interacts with MED1, NCOA1, NCOA2, NCOA3 CC and NCOA6 coactivators, leading to a strong increase of transcription CC of target genes. Interacts with the corepressor NCOR1. Interacts with CC SNW1. Interacts with IRX4, the interaction does not affect its CC transactivation activity (By similarity). Interacts with CRY1 CC (PubMed:28751364). Interacts with CRY2 in a ligand-dependent manner CC (PubMed:28751364). {ECO:0000250|UniProtKB:P11473, CC ECO:0000269|PubMed:28751364}. CC -!- INTERACTION: CC P48281; Q925T6: Grip1; NbExp=2; IntAct=EBI-346797, EBI-537752; CC P48281; Q64337: Sqstm1; NbExp=3; IntAct=EBI-346797, EBI-645025; CC P48281; Q00403: GTF2B; Xeno; NbExp=2; IntAct=EBI-346797, EBI-389564; CC P48281; Q9Y6Q9: NCOA3; Xeno; NbExp=2; IntAct=EBI-346797, EBI-81196; CC P48281; Q13573: SNW1; Xeno; NbExp=2; IntAct=EBI-346797, EBI-632715; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11473, CC ECO:0000255|PROSITE-ProRule:PRU00407}. Cytoplasm CC {ECO:0000250|UniProtKB:P11473}. Note=Localizes mainly to the nucleus. CC Translocated into the nucleus via both ligand-dependent and ligand- CC independent pathways; ligand-independent nuclear translocation is CC mediated by IPO4. {ECO:0000250|UniProtKB:P11473}. CC -!- INDUCTION: By 1,25-dihydroxyvitamin D(3) in kidney. CC {ECO:0000269|PubMed:14528024}. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain. CC {ECO:0000250|UniProtKB:P11473}. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000250|UniProtKB:P11473}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {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; D31969; BAA06737.1; -; mRNA. DR EMBL; AK030339; BAC26911.1; -; mRNA. DR EMBL; AK154647; BAE32738.1; -; mRNA. DR EMBL; CH466550; EDL04218.1; -; Genomic_DNA. DR EMBL; BC006716; AAH06716.1; -; mRNA. DR CCDS; CCDS27784.1; -. DR PIR; PC4019; PC4019. DR RefSeq; NP_033530.2; NM_009504.4. DR AlphaFoldDB; P48281; -. DR SMR; P48281; -. DR BioGRID; 204511; 6. DR ComplexPortal; CPX-673; RXRalpha-VDR nuclear hormone receptor complex. DR ComplexPortal; CPX-872; RXRbeta-VDR nuclear hormone receptor complex. DR CORUM; P48281; -. DR DIP; DIP-31478N; -. DR IntAct; P48281; 12. DR MINT; P48281; -. DR STRING; 10090.ENSMUSP00000023119; -. DR BindingDB; P48281; -. DR ChEMBL; CHEMBL5601; -. DR GlyGen; P48281; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P48281; -. DR PhosphoSitePlus; P48281; -. DR MaxQB; P48281; -. DR PaxDb; 10090-ENSMUSP00000023119; -. DR PeptideAtlas; P48281; -. DR ProteomicsDB; 300197; -. DR Pumba; P48281; -. DR Antibodypedia; 3902; 936 antibodies from 44 providers. DR DNASU; 22337; -. DR Ensembl; ENSMUST00000023119.15; ENSMUSP00000023119.9; ENSMUSG00000022479.16. DR GeneID; 22337; -. DR KEGG; mmu:22337; -. DR UCSC; uc007xlk.1; mouse. DR AGR; MGI:103076; -. DR CTD; 7421; -. DR MGI; MGI:103076; Vdr. DR VEuPathDB; HostDB:ENSMUSG00000022479; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000155473; -. DR HOGENOM; CLU_007368_12_0_1; -. DR InParanoid; P48281; -. DR OMA; DMSWDCG; -. DR OrthoDB; 5359733at2759; -. DR PhylomeDB; P48281; -. DR TreeFam; TF316304; -. DR Reactome; R-MMU-196791; Vitamin D (calciferol) metabolism. DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway. DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors. DR BioGRID-ORCS; 22337; 3 hits in 80 CRISPR screens. DR ChiTaRS; Vdr; mouse. DR PRO; PR:P48281; -. DR Proteomes; UP000000589; Chromosome 15. DR RNAct; P48281; Protein. DR Bgee; ENSMUSG00000022479; Expressed in duodenum and 138 other cell types or tissues. DR ExpressionAtlas; P48281; baseline and differential. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0001651; C:dense fibrillar component; ISO:MGI. DR GO; GO:0000791; C:euchromatin; ISO:MGI. DR GO; GO:0000792; C:heterochromatin; ISO:MGI. DR GO; GO:0016363; C:nuclear matrix; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI. DR GO; GO:0030315; C:T-tubule; ISO:MGI. DR GO; GO:1902098; F:calcitriol binding; ISO:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:1902121; F:lithocholic acid binding; ISO:MGI. DR GO; GO:0038186; F:lithocholic acid receptor activity; ISO:MGI. DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI. DR GO; GO:0005499; F:vitamin D binding; ISO:MGI. DR GO; GO:0070644; F:vitamin D response element binding; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0060057; P:apoptotic process involved in mammary gland involution; IMP:MGI. DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:MGI. DR GO; GO:0038183; P:bile acid signaling pathway; ISO:MGI. DR GO; GO:0006816; P:calcium ion transport; IMP:MGI. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0000902; P:cell morphogenesis; ISO:MGI. DR GO; GO:0046697; P:decidualization; IEA:Ensembl. DR GO; GO:0050892; P:intestinal absorption; IMP:MGI. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:MGI. DR GO; GO:0007595; P:lactation; IMP:MGI. DR GO; GO:0060745; P:mammary gland branching involved in pregnancy; IMP:MGI. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:MGI. DR GO; GO:1900155; P:negative regulation of bone trabecula formation; ISO:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; ISO:MGI. DR GO; GO:0030279; P:negative regulation of ossification; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0035435; P:phosphate ion transmembrane transport; ISO:MGI. DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IMP:MGI. DR GO; GO:0030501; P:positive regulation of bone mineralization; NAS:ComplexPortal. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:MGI. DR GO; GO:2000830; P:positive regulation of parathyroid hormone secretion; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; ISO:MGI. DR GO; GO:0060558; P:regulation of calcidiol 1-monooxygenase activity; IMP:BHF-UCL. DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:1903412; P:response to bile acid; ISO:MGI. DR GO; GO:0001501; P:skeletal system development; IMP:MGI. DR GO; GO:0070561; P:vitamin D receptor signaling pathway; ISS:UniProtKB. DR CDD; cd06955; NR_DBD_VDR; 1. DR CDD; cd06933; NR_LBD_VDR; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1. DR InterPro; IPR042153; DBD_VDR. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR000324; VitD_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1. DR PANTHER; PTHR24082:SF38; VITAMIN D3 RECEPTOR; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR PRINTS; PR00350; VITAMINDR. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P48281; MM. PE 1: Evidence at protein level; KW Cytoplasm; DNA-binding; Metal-binding; Nucleus; Receptor; KW Reference proteome; Transcription; Transcription regulation; Zinc; KW Zinc-finger. FT CHAIN 1..422 FT /note="Vitamin D3 receptor" FT /id="PRO_0000053543" FT DOMAIN 127..418 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 21..96 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 24..44 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 60..84 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 97..126 FT /note="Hinge" FT /evidence="ECO:0000250|UniProtKB:P11473" FT REGION 161..185 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 241..259 FT /note="Interaction with coactivator LXXLL motif" FT /evidence="ECO:0000250|UniProtKB:P13053" FT MOTIF 411..419 FT /note="9aaTAD" FT /evidence="ECO:0000250|UniProtKB:P11473" FT COMPBIAS 164..185 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 143 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000250|UniProtKB:P11473" FT BINDING 222..232 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000250|UniProtKB:P11473" FT BINDING 266..273 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000250|UniProtKB:P11473" FT BINDING 300 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000250|UniProtKB:P11473" FT BINDING 392 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000250|UniProtKB:P11473" FT CONFLICT 276 FT /note="L -> M (in Ref. 1; BAA06737)" FT /evidence="ECO:0000305" SQ SEQUENCE 422 AA; 47834 MW; 4614DD4A129F2732 CRC64; MEAMAASTSL PDPGDFDRNV PRICGVCGDR ATGFHFNAMT CEGCKGFFRR SMKRKALFTC PFNGDCRITK DNRRHCQACR LKRCVDIGMM KEFILTDEEV QRKREMIMKR KEEEALKDSL RPKLSEEQQH IIAILLDAHH KTYDPTYADF RDFRPPIRAD VSTGSYSPRP TLSFSGDSSS NSDLYTPSLD MMEPASFSTM DLNEEGSDDP SVTLDLSPLS MLPHLADLVS YSIQKVIGFA KMIPGFRDLT SDDQIVLLKS SAIEVIMLRS NQSFTLDDMS WDCGSQDYKY DITDVSRAGH TLELIEPLIK FQVGLKKLNL HEEEHVLLMA ICIVSPDRPG VQDAKLVEAI QDRLSNTLQT YIRCRHPPPG SHQLYAKMIQ KLADLRSLNE EHSKQYRSLS FQPENSMKLT PLVLEVFGNE IS //