ID VDR_HUMAN Reviewed; 427 AA. AC P11473; B2R5Q1; G3V1V9; Q5PSV3; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 27-MAR-2024, entry version 257. 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 {ECO:0000312|HGNC:HGNC:12679}; Synonyms=NR1I1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2835767; DOI=10.1073/pnas.85.10.3294; RA Baker A.R., McDonnell D.P., Hughes M., Crisp T.M., Mangelsdorf D.J., RA Haussler M.R., Pike J.W., Shine J., O'Malley B.W.; RT "Cloning and expression of full-length cDNA encoding human vitamin D RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 85:3294-3298(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1324736; DOI=10.1016/0167-4781(92)90063-6; RA Goto H., Chen K.S., Prahl J.M., Deluca H.F.; RT "A single receptor identical with that from intestine/T47D cells mediates RT the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells."; RL Biochim. Biophys. Acta 1132:103-108(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lens epithelium; RA Rae J.L., Shepard A.R.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9212063; DOI=10.1210/mend.11.8.9951; RA Miyamoto K., Kesterson R.A., Yamamoto H., Taketani Y., Nishiwaki E., RA Tatsumi S., Inoue Y., Morita K., Takeda E., Pike J.W.; RT "Structural organization of the human vitamin D receptor chromosomal gene RT and its promoter."; RL Mol. Endocrinol. 11:1165-1179(1997). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-230 AND ILE-362. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-90 (ISOFORM 1/2). RC TISSUE=Peripheral blood; RX PubMed=1850412; DOI=10.1016/s0021-9258(20)89488-5; RA Yu X.-P., Mocharla H., Hustmyer F.G., Manolagas S.C.; RT "Vitamin D receptor expression in human lymphocytes. Signal requirements RT and characterization by western blots and DNA sequencing."; RL J. Biol. Chem. 266:7588-7595(1991). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 343-427. RX PubMed=16252240; DOI=10.1086/497438; RA Fang Y., van Meurs J.B., d'Alesio A., Jhamai M., Zhao H., Rivadeneira F., RA Hofman A., van Leeuwen J.P., Jehan F., Pols H.A., Uitterlinden A.G.; RT "Promoter and 3'-untranslated-region haplotypes in the vitamin D receptor RT gene predispose to osteoporotic fracture: the Rotterdam study."; RL Am. J. Hum. Genet. 77:807-823(2005). RN [12] RP INTERACTION WITH NCOA3. RX PubMed=9267036; DOI=10.1016/s0092-8674(00)80516-4; RA Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., RA Privalsky M.L., Nakatani Y., Evans R.M.; RT "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and RT forms a multimeric activation complex with P/CAF and CBP/p300."; RL Cell 90:569-580(1997). RN [13] RP INTERACTION WITH SNW1. RX PubMed=9632709; DOI=10.1074/jbc.273.26.16434; RA Baudino T.A., Kraichely D.M., Jefcoat S.C. Jr., Winchester S.K., RA Partridge N.C., Macdonald P.N.; RT "Isolation and characterization of a novel coactivator protein, NCoA-62, RT involved in vitamin D-mediated transcription."; RL J. Biol. Chem. 273:16434-16441(1998). RN [14] RP INTERACTION WITH NCOA6. RX PubMed=10866662; DOI=10.1128/mcb.20.14.5048-5063.2000; RA Mahajan M.A., Samuels H.H.; RT "A new family of nuclear receptor coregulators that integrates nuclear RT receptor signaling through CBP."; RL Mol. Cell. Biol. 20:5048-5063(2000). RN [15] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 47-PHE-PHE-48. RX PubMed=12145331; DOI=10.1210/me.2001-0345; RA Pruefer K., Barsony J.; RT "Retinoid X receptor dominates the nuclear import and export of the RT unliganded vitamin D receptor."; RL Mol. Endocrinol. 16:1738-1751(2002). RN [16] 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 [17] RP RETRACTED PAPER. RX PubMed=16252006; DOI=10.1038/sj.emboj.7600853; RA Fujiki R., Kim M.-S., Sasaki Y., Yoshimura K., Kitagawa H., Kato S.; RT "Ligand-induced transrepression by VDR through association of WSTF with RT acetylated histones."; RL EMBO J. 24:3881-3894(2005). RN [18] RP RETRACTION NOTICE OF PUBMED:16252006. RX PubMed=25452584; DOI=10.15252/embj.201470110; RA Fujiki R., Kim M.-S., Sasaki Y., Yoshimura K., Kitagawa H., Kato S.; RT "Retraction: 'Ligand-induced transrepression by VDR through association of RT WSTF with acetylated histones'."; RL EMBO J. 33:2881-2881(2014). RN [19] RP SUBCELLULAR LOCATION. RX PubMed=16207705; DOI=10.1074/jbc.m509347200; RA Miyauchi Y., Michigami T., Sakaguchi N., Sekimoto T., Yoneda Y., Pike J.W., RA Yamagata M., Ozono K.; RT "Importin 4 is responsible for ligand-independent nuclear translocation of RT vitamin D receptor."; RL J. Biol. Chem. 280:40901-40908(2005). RN [20] RP INTERACTION WITH IRX4. RC TISSUE=Prostate; RX PubMed=22323358; DOI=10.1093/hmg/dds025; RA Nguyen H.H., Takata R., Akamatsu S., Shigemizu D., Tsunoda T., Furihata M., RA Takahashi A., Kubo M., Kamatani N., Ogawa O., Fujioka T., Nakamura Y., RA Nakagawa H.; RT "IRX4 at 5p15 suppresses prostate cancer growth through the interaction RT with vitamin D receptor, conferring prostate cancer susceptibility."; RL Hum. Mol. Genet. 21:2076-2085(2012). RN [21] RP 9AATAD MOTIF. RX PubMed=30468856; DOI=10.1016/j.jsbmb.2018.11.008; RA Piskacek M., Havelka M., Jendruchova K., Knight A.; RT "Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA RT activation pathways."; RL J. Steroid Biochem. Mol. Biol. 187:118-123(2019). RN [22] 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). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 118-427 IN COMPLEX WITH RP DIHYDROXYVITAMIN D3, IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION. RX PubMed=10678179; DOI=10.1016/s1097-2765(00)80413-x; RA Rochel N., Wurtz J.-M., Mitschler A., Klaholz B., Moras D.; RT "The crystal structure of the nuclear receptor for vitamin D bound to its RT natural ligand."; RL Mol. Cell 5:173-179(2000). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 118-427 IN COMPLEXES WITH VITAMIN RP D3 AND VITAMIN D3 ANALOGS. RX PubMed=11344298; DOI=10.1073/pnas.091018698; RA Tocchini-Valentini G., Rochel N., Wurtz J.-M., Mitschler A., Moras D.; RT "Crystal structures of the vitamin D receptor complexed to superagonist 20- RT epi ligands."; RL Proc. Natl. Acad. Sci. U.S.A. 98:5491-5496(2001). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 16-125 IN COMPLEX WITH DNA, RP MUTAGENESIS OF 61-PRO-PHE-62 AND HIS-75, AND SUBUNIT. RX PubMed=11980721; DOI=10.1093/emboj/21.9.2242; RA Shaffer P.L., Gewirth D.T.; RT "Structural basis of VDR-DNA interactions on direct repeat response RT elements."; RL EMBO J. 21:2242-2252(2002). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 188-427 IN COMPLEXES WITH VITAMIN RP D3 ANALOGS. RX PubMed=15055995; DOI=10.1021/jm0310582; RA Tocchini-Valentini G., Rochel N., Wurtz J.-M., Moras D.; RT "Crystal structures of the vitamin D nuclear receptor liganded with the RT vitamin D side chain analogues calcipotriol and seocalcitol, receptor RT agonists of clinical importance. Insights into a structural basis for the RT switching of calcipotriol to a receptor antagonist by further side chain RT modification."; RL J. Med. Chem. 47:1956-1961(2004). RN [27] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 16-125 OF MUTANT RP ALA-61/ALA-62/ALA-75 IN COMPLEX WITH RXRA AND DNA, AND SUBUNIT. RX PubMed=15225774; DOI=10.1016/j.jsbmb.2004.03.084; RA Shaffer P.L., Gewirth D.T.; RT "Structural analysis of RXR-VDR interactions on DR3 DNA."; RL J. Steroid Biochem. Mol. Biol. 89:215-219(2004). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 188-427 IN COMPLEX WITH VITAMIN D3 RP ANALOG, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RP NCOA1; NCOA2 AND MED1. RX PubMed=15728261; DOI=10.1124/mol.104.008730; RA Eelen G., Verlinden L., Rochel N., Claessens F., De Clercq P., RA Vandewalle M., Tocchini-Valentini G., Moras D., Bouillon R., Verstuyf A.; RT "Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D RT explained by vitamin D receptor-coactivator interaction."; RL Mol. Pharmacol. 67:1566-1573(2005). RN [29] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 188-427 IN COMPLEXES WITH RP DIHYDROXYVITAMIN D3 AND VITAMIN D3 ANALOGS, AND FUNCTION. RX PubMed=16913708; DOI=10.1021/jm0604070; RA Hourai S., Fujishima T., Kittaka A., Suhara Y., Takayama H., Rochel N., RA Moras D.; RT "Probing a water channel near the A-ring of receptor-bound 1 alpha,25- RT dihydroxyvitamin D3 with selected 2 alpha-substituted analogues."; RL J. Med. Chem. 49:5199-5205(2006). RN [30] RP VARIANTS VDDR2A ASP-33 AND GLN-73. RX PubMed=2849209; DOI=10.1126/science.2849209; RA Hughes M.R., Malloy P.J., Kieback D.G., Kesterson R.A., Pike J.W., RA Feldman D., O'Malley B.W.; RT "Point mutations in the human vitamin D receptor gene associated with RT hypocalcemic rickets."; RL Science 242:1702-1705(1988). RN [31] RP VARIANT VDDR2A GLN-35. RX PubMed=8381803; DOI=10.1210/jcem.76.2.8381803; RA Yagi H., Ozono K., Miyake H., Nagashima K., Kuroume T., Pike J.W.; RT "A new point mutation in the deoxyribonucleic acid-binding domain of the RT vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D- RT resistant rickets."; RL J. Clin. Endocrinol. Metab. 76:509-512(1993). RN [32] RP VARIANT VDDR2A GLN-50. RX PubMed=1652893; RA Saijo T., Ito M., Takeda E., Mahbubul Huq A.H.M., Naito E., Yokota I., RA Sone T., Pike J.W., Kuroda Y.; RT "A unique mutation in the vitamin D receptor gene in three Japanese RT patients with vitamin D-dependent rickets type II: utility of single-strand RT conformation polymorphism analysis for heterozygous carrier detection."; RL Am. J. Hum. Genet. 49:668-673(1991). RN [33] RP VARIANT VDDR2A GLN-80. RX PubMed=2177843; DOI=10.1210/mend-4-4-623; RA Sone T., Marx S.J., Liberman U.A., Pike J.W.; RT "A unique point mutation in the human vitamin D receptor chromosomal gene RT confers hereditary resistance to 1,25-dihydroxyvitamin D3."; RL Mol. Endocrinol. 4:623-631(1990). RN [34] RP VARIANT VDDR2A GLN-80. RX PubMed=8106618; DOI=10.1210/jcem.78.2.8106618; RA Malloy P.J., Weisman Y., Feldman D.; RT "Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from RT a mutation in the vitamin D receptor deoxyribonucleic acid-binding RT domain."; RL J. Clin. Endocrinol. Metab. 78:313-316(1994). RN [35] RP VARIANTS VDDR2A 152-GLN--SER-427 DEL AND LEU-274. RX PubMed=8392085; DOI=10.1172/jci116539; RA Kristjansson K., Rut A.R., Hewison M., O'Riordan J.L.H., Hughes M.R.; RT "Two mutations in the hormone binding domain of the vitamin D receptor RT cause tissue resistance to 1,25 dihydroxyvitamin D3."; RL J. Clin. Invest. 92:12-16(1993). RN [36] RP VARIANTS VDDR2A GLU-45 AND ILE-47. RX PubMed=7828346; DOI=10.1111/j.1365-2265.1994.tb01822.x; RA Rut A.R., Hewison M., Kristjansson K., Luisi B., Hughes M.R., RA O'Riordan J.L.H.; RT "Two mutations causing vitamin D resistant rickets: modelling on the basis RT of steroid hormone receptor DNA-binding domain crystal structures."; RL Clin. Endocrinol. (Oxf.) 41:581-590(1994). RN [37] RP VARIANT VDDR2A ASP-46. RX PubMed=8675579; DOI=10.1210/jcem.81.7.8675579; RA Lin U.-T., Malloy P.J., Sakati N., Al-Ashwal A., Feldman D.; RT "A novel mutation in the deoxyribonucleic acid-binding domain of the RT vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant RT rickets."; RL J. Clin. Endocrinol. Metab. 81:2564-2569(1996). RN [38] RP VARIANTS VDDR2A SER-314 AND CYS-391. RX PubMed=8961271; DOI=10.1210/mend.10.12.8961271; RA Whitfield G.K., Selznick S.H., Haussler C.A., Hsieh J.-C., Galligan M.A., RA Jurutka P.W., Thompson P.D., Lee S.M., Zerwekh J.E., Haussler M.R.; RT "Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin RT D(3): point mutations confer reduced transactivation in response to ligand RT and impaired interaction with the retinoid X receptor heterodimeric RT partner."; RL Mol. Endocrinol. 10:1617-1631(1996). RN [39] RP VARIANT VDDR2A GLN-305. RX PubMed=9005998; DOI=10.1172/jci119158; RA Malloy P.J., Eccleshall T.R., Gross C., van Maldergem L., Bouillon R., RA Feldman D.; RT "Hereditary vitamin D resistant rickets caused by a novel mutation in the RT vitamin D receptor that results in decreased affinity for hormone and RT cellular hyporesponsiveness."; RL J. Clin. Invest. 99:297-304(1997). RN [40] RP INVOLVEMENT IN MYCOBACTERIUM TUBERCULOSIS SUSCEPTIBILITY. RX PubMed=15032981; DOI=10.1111/j..2004.00183.x; RA Selvaraj P., Kurian S.M., Chandra G., Reetha A.M., Charles N., RA Narayanan P.R.; RT "Vitamin D receptor gene variants of BsmI, ApaI, TaqI, and FokI RT polymorphisms in spinal tuberculosis."; RL Clin. Genet. 65:73-76(2004). RN [41] RP VARIANT VDDR2A MET-346. RX PubMed=17970811; DOI=10.1111/j.1365-2133.2007.08232.x; RA Arita K., Nanda A., Wessagowit V., Akiyama M., Alsaleh Q.A., McGrath J.A.; RT "A novel mutation in the VDR gene in hereditary vitamin D-resistant RT rickets."; RL Br. J. Dermatol. 158:168-171(2008). RN [42] RP VARIANT VDDR2A PRO-360, CHARACTERIZATION OF VARIANT VDDR2A 152-GLN--SER-427 RP DEL; LEU-274; GLN-305; MET-346 AND PRO-360, FUNCTION, INTERACTION WITH RP NCOA1; NCOR1 AND RXR, AND SUBCELLULAR LOCATION. RX PubMed=28698609; DOI=10.1038/s41598-017-05081-x; RA Tamura M., Ishizawa M., Isojima T., Oezen S., Oka A., Makishima M., RA Kitanaka S.; RT "Functional analyses of a novel missense and other mutations of the vitamin RT D receptor in association with alopecia."; RL Sci. Rep. 7:5102-5102(2017). CC -!- FUNCTION: Nuclear receptor for calcitriol, the active form of vitamin CC D3 which mediates the action of this vitamin on cells (PubMed:28698609, CC PubMed:16913708, PubMed:15728261, PubMed:10678179). Enters the nucleus CC upon vitamin D3 binding where it forms heterodimers with the retinoid X CC receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to CC specific response elements on DNA and activate the transcription of CC vitamin D3-responsive target genes (PubMed:28698609). Plays a central CC role in calcium homeostasis (By similarity). Also functions as a CC receptor for the secondary bile acid lithocholic acid (LCA) and its CC metabolites (PubMed:12016314, PubMed:32354638). CC {ECO:0000250|UniProtKB:P13053, ECO:0000269|PubMed:10678179, CC ECO:0000269|PubMed:12016314, ECO:0000269|PubMed:15728261, CC ECO:0000269|PubMed:16913708, ECO:0000269|PubMed:28698609, CC ECO:0000269|PubMed:32354638}. CC -!- SUBUNIT: Homodimer in the absence of bound vitamin D3 CC (PubMed:11980721). Heterodimer with RXRA after vitamin D3 binding CC (PubMed:15225774, PubMed:11980721, PubMed:10678179). Interacts with CC MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong CC increase of transcription of target genes (PubMed:10866662, CC PubMed:15728261, PubMed:28698609, PubMed:9267036). Interacts with the CC corepressor NCOR1 (PubMed:28698609). Interacts with SNW1 CC (PubMed:9632709). Interacts with IRX4, the interaction does not affect CC its transactivation activity (PubMed:22323358). Interacts with CRY1 (By CC similarity). Interacts with CRY2 in a ligand-dependent manner (By CC similarity). {ECO:0000250|UniProtKB:P48281, CC ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:10866662, CC ECO:0000269|PubMed:11980721, ECO:0000269|PubMed:15225774, CC ECO:0000269|PubMed:15728261, ECO:0000269|PubMed:22323358, CC ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:9267036, CC ECO:0000269|PubMed:9632709}. CC -!- INTERACTION: CC P11473; Q09472: EP300; NbExp=3; IntAct=EBI-286357, EBI-447295; CC P11473; Q15648: MED1; NbExp=4; IntAct=EBI-286357, EBI-394459; CC P11473; P50222: MEOX2; NbExp=3; IntAct=EBI-286357, EBI-748397; CC P11473; Q15788: NCOA1; NbExp=3; IntAct=EBI-286357, EBI-455189; CC P11473; P26045: PTPN3; NbExp=4; IntAct=EBI-286357, EBI-1047946; CC P11473; P19793: RXRA; NbExp=6; IntAct=EBI-286357, EBI-78598; CC P11473; Q13573: SNW1; NbExp=5; IntAct=EBI-286357, EBI-632715; CC P11473; Q13501: SQSTM1; NbExp=4; IntAct=EBI-286357, EBI-307104; CC P11473; P04637: TP53; NbExp=6; IntAct=EBI-286357, EBI-366083; CC P11473; Q15645: TRIP13; NbExp=3; IntAct=EBI-286357, EBI-358993; CC P11473; Q9JLI4: Ncoa6; Xeno; NbExp=2; IntAct=EBI-286357, EBI-286271; CC P11473; P28700: Rxra; Xeno; NbExp=3; IntAct=EBI-286357, EBI-346715; CC P11473-2; X5D778: ANKRD11; NbExp=3; IntAct=EBI-12874016, EBI-17183751; CC P11473-2; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-12874016, EBI-741158; CC P11473-2; Q01804: OTUD4; NbExp=3; IntAct=EBI-12874016, EBI-1054396; CC P11473-2; Q96S38: RPS6KC1; NbExp=3; IntAct=EBI-12874016, EBI-347731; CC P11473-2; P48443: RXRG; NbExp=4; IntAct=EBI-12874016, EBI-712405; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, CC ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:16207705, CC ECO:0000269|PubMed:28698609}. Cytoplasm {ECO:0000269|PubMed:12145331, CC ECO:0000269|PubMed:16207705, ECO:0000269|PubMed:28698609}. CC Note=Localizes mainly to the nucleus (PubMed:28698609, CC PubMed:12145331). Translocated into the nucleus via both ligand- CC dependent and ligand-independent pathways; ligand-independent nuclear CC translocation is mediated by IPO4 (PubMed:16207705). CC {ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:16207705, CC ECO:0000269|PubMed:28698609}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11473-1; Sequence=Displayed; CC Name=2; CC IsoId=P11473-2; Sequence=VSP_047218; 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:0000269|PubMed:10678179}. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000305|PubMed:30468856}. CC -!- POLYMORPHISM: Genetic variations in VDR may determine Mycobacterium CC tuberculosis susceptibility [MIM:607948]. CC {ECO:0000269|PubMed:15032981}. CC -!- DISEASE: Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A CC disorder of vitamin D metabolism resulting in severe rickets, CC hypocalcemia and secondary hyperparathyroidism. Most patients have CC total alopecia in addition to rickets. {ECO:0000269|PubMed:1652893, CC ECO:0000269|PubMed:17970811, ECO:0000269|PubMed:2177843, CC ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:28698609, CC ECO:0000269|PubMed:7828346, ECO:0000269|PubMed:8106618, CC ECO:0000269|PubMed:8381803, ECO:0000269|PubMed:8392085, CC ECO:0000269|PubMed:8675579, ECO:0000269|PubMed:8961271, CC ECO:0000269|PubMed:9005998}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator. CC {ECO:0000305}. CC -!- CAUTION: Was thought to be recruited to promoters via its interaction CC with BAZ1B/WSTF, but this work has later been retracted. CC {ECO:0000305|PubMed:16252006, ECO:0000305|PubMed:25452584}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH60832.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAP88938.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/vdr/"; 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; J03258; AAA61273.1; -; mRNA. DR EMBL; X67482; CAA47824.1; -; mRNA. DR EMBL; AF026260; AAB95155.1; -; mRNA. DR EMBL; AB002168; BAA83389.1; -; Genomic_DNA. DR EMBL; AY342401; AAP88938.1; ALT_SEQ; Genomic_DNA. DR EMBL; AK312267; BAG35198.1; -; mRNA. DR EMBL; AC004466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC121338; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471111; EAW57960.1; -; Genomic_DNA. DR EMBL; CH471111; EAW57961.1; -; Genomic_DNA. DR EMBL; BC060832; AAH60832.1; ALT_INIT; mRNA. DR EMBL; M65208; AAA61274.1; -; mRNA. DR EMBL; AY827087; AAV85448.1; -; Genomic_DNA. DR CCDS; CCDS55820.1; -. [P11473-2] DR CCDS; CCDS8757.1; -. [P11473-1] DR PIR; A28200; A28200. DR RefSeq; NP_000367.1; NM_000376.2. [P11473-1] DR RefSeq; NP_001017535.1; NM_001017535.1. [P11473-1] DR RefSeq; NP_001017536.1; NM_001017536.1. [P11473-2] DR RefSeq; XP_006719650.1; XM_006719587.3. DR RefSeq; XP_011537022.1; XM_011538720.2. DR PDB; 1DB1; X-ray; 1.80 A; A=118-427. DR PDB; 1IE8; X-ray; 1.52 A; A=118-427. DR PDB; 1IE9; X-ray; 1.40 A; A=118-427. DR PDB; 1KB2; X-ray; 2.70 A; A/B=16-125. DR PDB; 1KB4; X-ray; 2.80 A; A/B=16-125. DR PDB; 1KB6; X-ray; 2.70 A; A/B=16-125. DR PDB; 1S0Z; X-ray; 2.50 A; A=118-427. DR PDB; 1S19; X-ray; 2.10 A; A=118-427. DR PDB; 1TXI; X-ray; 1.90 A; A=118-427. DR PDB; 1YNW; X-ray; 3.00 A; A=16-125. DR PDB; 2HAM; X-ray; 1.90 A; A=118-427. DR PDB; 2HAR; X-ray; 1.90 A; A=118-427. DR PDB; 2HAS; X-ray; 1.96 A; A=118-427. DR PDB; 2HB7; X-ray; 1.80 A; A=118-427. DR PDB; 2HB8; X-ray; 2.00 A; A=118-427. DR PDB; 3A2I; X-ray; 3.27 A; A=118-427. DR PDB; 3A2J; X-ray; 2.70 A; A=118-427. DR PDB; 3A3Z; X-ray; 1.72 A; X=118-427. DR PDB; 3A40; X-ray; 1.45 A; X=118-427. DR PDB; 3A78; X-ray; 1.90 A; A=118-427. DR PDB; 3AUQ; X-ray; 2.64 A; A=118-427. DR PDB; 3AUR; X-ray; 2.21 A; A=118-427. DR PDB; 3AX8; X-ray; 2.60 A; A=118-427. DR PDB; 3AZ1; X-ray; 1.50 A; A=120-423. DR PDB; 3AZ2; X-ray; 1.69 A; A=120-423. DR PDB; 3AZ3; X-ray; 1.36 A; A=120-423. DR PDB; 3B0T; X-ray; 1.30 A; A=120-423. DR PDB; 3CS4; X-ray; 2.00 A; A=118-427. DR PDB; 3CS6; X-ray; 1.80 A; A=118-427. DR PDB; 3KPZ; X-ray; 1.90 A; A=118-427. DR PDB; 3M7R; X-ray; 1.80 A; A=120-423. DR PDB; 3OGT; X-ray; 1.75 A; A=118-427. DR PDB; 3P8X; X-ray; 1.70 A; A=118-164, A=217-427. DR PDB; 3TKC; X-ray; 1.75 A; A=118-427. DR PDB; 3VHW; X-ray; 2.43 A; A=118-427. DR PDB; 3W0A; X-ray; 1.80 A; A=120-423. DR PDB; 3W0C; X-ray; 1.90 A; A=120-423. DR PDB; 3W0Y; X-ray; 1.98 A; A=120-423. DR PDB; 3WGP; X-ray; 2.00 A; A=120-423. DR PDB; 3WWR; X-ray; 3.18 A; A=118-427. DR PDB; 3X31; X-ray; 2.11 A; A=118-427. DR PDB; 3X36; X-ray; 1.93 A; A=118-427. DR PDB; 4G2I; X-ray; 1.80 A; A=118-427. DR PDB; 4ITE; X-ray; 2.49 A; A=118-427. DR PDB; 4ITF; X-ray; 2.84 A; A=118-427. DR PDB; 5GT4; X-ray; 1.83 A; A=118-423. DR PDB; 5V39; X-ray; 2.20 A; A=119-425. DR PDB; 5YSY; X-ray; 2.00 A; A=118-423. DR PDB; 5YT2; X-ray; 2.00 A; A=118-423. DR PDB; 7QPP; X-ray; 1.52 A; A=118-427. DR PDBsum; 1DB1; -. DR PDBsum; 1IE8; -. DR PDBsum; 1IE9; -. DR PDBsum; 1KB2; -. DR PDBsum; 1KB4; -. DR PDBsum; 1KB6; -. DR PDBsum; 1S0Z; -. DR PDBsum; 1S19; -. DR PDBsum; 1TXI; -. DR PDBsum; 1YNW; -. DR PDBsum; 2HAM; -. DR PDBsum; 2HAR; -. DR PDBsum; 2HAS; -. DR PDBsum; 2HB7; -. DR PDBsum; 2HB8; -. DR PDBsum; 3A2I; -. DR PDBsum; 3A2J; -. DR PDBsum; 3A3Z; -. DR PDBsum; 3A40; -. DR PDBsum; 3A78; -. DR PDBsum; 3AUQ; -. DR PDBsum; 3AUR; -. DR PDBsum; 3AX8; -. DR PDBsum; 3AZ1; -. DR PDBsum; 3AZ2; -. DR PDBsum; 3AZ3; -. DR PDBsum; 3B0T; -. DR PDBsum; 3CS4; -. DR PDBsum; 3CS6; -. DR PDBsum; 3KPZ; -. DR PDBsum; 3M7R; -. DR PDBsum; 3OGT; -. DR PDBsum; 3P8X; -. DR PDBsum; 3TKC; -. DR PDBsum; 3VHW; -. DR PDBsum; 3W0A; -. DR PDBsum; 3W0C; -. DR PDBsum; 3W0Y; -. DR PDBsum; 3WGP; -. DR PDBsum; 3WWR; -. DR PDBsum; 3X31; -. DR PDBsum; 3X36; -. DR PDBsum; 4G2I; -. DR PDBsum; 4ITE; -. DR PDBsum; 4ITF; -. DR PDBsum; 5GT4; -. DR PDBsum; 5V39; -. DR PDBsum; 5YSY; -. DR PDBsum; 5YT2; -. DR PDBsum; 7QPP; -. DR AlphaFoldDB; P11473; -. DR SMR; P11473; -. DR BioGRID; 113264; 198. DR ComplexPortal; CPX-631; RXRalpha-VDR nuclear hormone receptor complex. DR ComplexPortal; CPX-871; RXRbeta-VDR nuclear hormone receptor complex. DR CORUM; P11473; -. DR DIP; DIP-32624N; -. DR ELM; P11473; -. DR IntAct; P11473; 34. DR MINT; P11473; -. DR BindingDB; P11473; -. DR ChEMBL; CHEMBL1977; -. DR DrugBank; DB07530; (1R,3R)-5-[(2E)-3-{(1S,3R)-2,2,3-trimethyl-3-[6,6,6-trifluoro-5-hydroxy-5-(trifluoromethyl)hex-3-yn-1-yl]cyclopentyl}prop-2-en-1-ylidene]cyclohexane-1,3-diol. DR DrugBank; DB08742; 1,3-CYCLOHEXANEDIOL, 4-METHYLENE-5-[(2E)-[(1S,3AS,7AS)-OCTAHYDRO-1-(5-HYDROXY-5-METHYL-1,3-HEXADIYNYL)-7A-METHYL-4H-INDEN-4-YLIDENE]ETHYLIDENE]-, (1R,3S,5Z). DR DrugBank; DB01436; Alfacalcidol. DR DrugBank; DB04891; Becocalcidiol. DR DrugBank; DB00146; Calcifediol. DR DrugBank; DB02300; Calcipotriol. DR DrugBank; DB00136; Calcitriol. DR DrugBank; DB00169; Cholecalciferol. DR DrugBank; DB04540; Cholesterol. DR DrugBank; DB05024; CTA018. DR DrugBank; DB11672; Curcumin. DR DrugBank; DB14635; Curcumin sulfate. DR DrugBank; DB01070; Dihydrotachysterol. DR DrugBank; DB06410; Doxercalciferol. DR DrugBank; DB05295; Eldecalcitol. DR DrugBank; DB06194; Elocalcitol. DR DrugBank; DB00153; Ergocalciferol. DR DrugBank; DB04796; Inecalcitol. DR DrugBank; DB03451; Lexacalcitol. DR DrugBank; DB00910; Paricalcitol. DR DrugBank; DB04258; Seocalcitol. DR DrugBank; DB11094; Vitamin D. DR DrugCentral; P11473; -. DR GuidetoPHARMACOLOGY; 605; -. DR SwissLipids; SLP:000001571; -. DR MoonDB; P11473; Predicted. DR TCDB; 9.B.208.1.1; the vitamin d3 receptor (vdr) family. DR GlyGen; P11473; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11473; -. DR PhosphoSitePlus; P11473; -. DR BioMuta; VDR; -. DR DMDM; 137617; -. DR EPD; P11473; -. DR jPOST; P11473; -. DR MassIVE; P11473; -. DR MaxQB; P11473; -. DR PaxDb; 9606-ENSP00000447173; -. DR PeptideAtlas; P11473; -. DR ProteomicsDB; 32456; -. DR ProteomicsDB; 52780; -. [P11473-1] DR Pumba; P11473; -. DR Antibodypedia; 3902; 936 antibodies from 44 providers. DR DNASU; 7421; -. DR Ensembl; ENST00000395324.6; ENSP00000378734.2; ENSG00000111424.12. [P11473-1] DR Ensembl; ENST00000549336.6; ENSP00000449573.2; ENSG00000111424.12. [P11473-1] DR Ensembl; ENST00000550325.5; ENSP00000447173.1; ENSG00000111424.12. [P11473-2] DR GeneID; 7421; -. DR KEGG; hsa:7421; -. DR MANE-Select; ENST00000549336.6; ENSP00000449573.2; NM_000376.3; NP_000367.1. DR UCSC; uc001rql.4; human. [P11473-1] DR AGR; HGNC:12679; -. DR CTD; 7421; -. DR DisGeNET; 7421; -. DR GeneCards; VDR; -. DR HGNC; HGNC:12679; VDR. DR HPA; ENSG00000111424; Tissue enriched (parathyroid). DR MalaCards; VDR; -. DR MIM; 277440; phenotype. DR MIM; 601769; gene. DR MIM; 607948; phenotype. DR neXtProt; NX_P11473; -. DR OpenTargets; ENSG00000111424; -. DR Orphanet; 93160; Hypocalcemic vitamin D-resistant rickets. DR PharmGKB; PA37301; -. DR VEuPathDB; HostDB:ENSG00000111424; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000155473; -. DR InParanoid; P11473; -. DR OMA; DMSWDCG; -. DR OrthoDB; 5359733at2759; -. DR PhylomeDB; P11473; -. DR TreeFam; TF316304; -. DR PathwayCommons; P11473; -. DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR SignaLink; P11473; -. DR SIGNOR; P11473; -. DR BioGRID-ORCS; 7421; 13 hits in 1177 CRISPR screens. DR ChiTaRS; VDR; human. DR EvolutionaryTrace; P11473; -. DR GeneWiki; Calcitriol_receptor; -. DR GenomeRNAi; 7421; -. DR Pharos; P11473; Tclin. DR PRO; PR:P11473; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P11473; Protein. DR Bgee; ENSG00000111424; Expressed in tibia and 151 other cell types or tissues. DR ExpressionAtlas; P11473; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL. DR GO; GO:1902098; F:calcitriol binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:1902121; F:lithocholic acid binding; IDA:UniProtKB. DR GO; GO:0038186; F:lithocholic acid receptor activity; IDA:UniProtKB. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0060057; P:apoptotic process involved in mammary gland involution; IEA:Ensembl. DR GO; GO:0038183; P:bile acid signaling pathway; IDA:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0000902; P:cell morphogenesis; IMP:UniProtKB. DR GO; GO:0046697; P:decidualization; IEP:BHF-UCL. DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0007595; P:lactation; IEA:Ensembl. DR GO; GO:0060745; P:mammary gland branching involved in pregnancy; IEA:Ensembl. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0035435; P:phosphate ion transmembrane transport; IDA:UniProt. DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IEA:Ensembl. DR GO; GO:0030501; P:positive regulation of bone mineralization; NAS:ComplexPortal. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; IDA:BHF-UCL. DR GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; IDA:ComplexPortal. DR GO; GO:0060558; P:regulation of calcidiol 1-monooxygenase activity; ISS:BHF-UCL. DR GO; GO:1903412; P:response to bile acid; IDA:UniProt. DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl. DR GO; GO:0070561; P:vitamin D receptor signaling pathway; IDA:BHF-UCL. 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; P11473; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW DNA-binding; Metal-binding; Nucleus; Receptor; Reference proteome; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..427 FT /note="Vitamin D3 receptor" FT /id="PRO_0000053542" FT DOMAIN 127..423 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:0000269|PubMed:10678179" FT REGION 158..190 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 246..264 FT /note="Interaction with coactivator LXXLL motif" FT /evidence="ECO:0000250|UniProtKB:P13053" FT MOTIF 416..424 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:30468856" FT COMPBIAS 165..190 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:0000269|PubMed:10678179, FT ECO:0000269|PubMed:11344298" FT BINDING 227..237 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000269|PubMed:10678179, FT ECO:0000269|PubMed:11344298" FT BINDING 271..278 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000269|PubMed:10678179, FT ECO:0000269|PubMed:11344298" FT BINDING 305 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000269|PubMed:10678179, FT ECO:0000269|PubMed:11344298" FT BINDING 397 FT /ligand="calciol" FT /ligand_id="ChEBI:CHEBI:28940" FT /evidence="ECO:0000269|PubMed:10678179, FT ECO:0000269|PubMed:11344298" FT VAR_SEQ 1 FT /note="M -> MEWRNKKRSDWLSMVLRTAGVEEAFGSEVSVRPHRRAPLGSTYLPPA FT PSGM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_047218" FT VARIANT 33 FT /note="G -> D (in VDDR2A; dbSNP:rs121909790)" FT /evidence="ECO:0000269|PubMed:2849209" FT /id="VAR_004656" FT VARIANT 35 FT /note="H -> Q (in VDDR2A)" FT /evidence="ECO:0000269|PubMed:8381803" FT /id="VAR_004657" FT VARIANT 45 FT /note="K -> E (in VDDR2A)" FT /evidence="ECO:0000269|PubMed:7828346" FT /id="VAR_004658" FT VARIANT 46 FT /note="G -> D (in VDDR2A; dbSNP:rs121909797)" FT /evidence="ECO:0000269|PubMed:8675579" FT /id="VAR_004659" FT VARIANT 47 FT /note="F -> I (in VDDR2A)" FT /evidence="ECO:0000269|PubMed:7828346" FT /id="VAR_004660" FT VARIANT 50 FT /note="R -> Q (in VDDR2A; dbSNP:rs121909794)" FT /evidence="ECO:0000269|PubMed:1652893" FT /id="VAR_004661" FT VARIANT 73 FT /note="R -> Q (in VDDR2A; dbSNP:rs121909791)" FT /evidence="ECO:0000269|PubMed:2849209" FT /id="VAR_004662" FT VARIANT 80 FT /note="R -> Q (in VDDR2A; dbSNP:rs121909793)" FT /evidence="ECO:0000269|PubMed:2177843, FT ECO:0000269|PubMed:8106618" FT /id="VAR_004663" FT VARIANT 152..427 FT /note="Missing (in VDDR2A; loss of calcitriol receptor FT activity; loss of affinity for calcitriol; no effect on FT ligand-independent localization to the nucleus; FT dbSNP:rs121909795)" FT /evidence="ECO:0000269|PubMed:28698609, FT ECO:0000269|PubMed:8392085" FT /id="VAR_079325" FT VARIANT 230 FT /note="L -> V (in dbSNP:rs11574090)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029309" FT VARIANT 274 FT /note="R -> L (in VDDR2A; loss of calcitriol receptor FT activity; decreased affinity for calcitriol by a factor of FT 1000; no effect on interaction with RXRA; changed FT interaction with NCOR1; loss of interaction with NCOA1; no FT effect on sequence-specific DNA-binding; FT dbSNP:rs121909796)" FT /evidence="ECO:0000269|PubMed:28698609, FT ECO:0000269|PubMed:8392085" FT /id="VAR_004664" FT VARIANT 305 FT /note="H -> Q (in VDDR2A; loss of calcitriol receptor FT activity; no effect on interaction with RXRA; changed FT interaction with NCOR1; loss of interaction with NCOA1; no FT effect on sequence-specific DNA-binding; FT dbSNP:rs121909798)" FT /evidence="ECO:0000269|PubMed:28698609, FT ECO:0000269|PubMed:9005998" FT /id="VAR_004665" FT VARIANT 314 FT /note="I -> S (in VDDR2A; dbSNP:rs121909799)" FT /evidence="ECO:0000269|PubMed:8961271" FT /id="VAR_004666" FT VARIANT 346 FT /note="V -> M (in VDDR2A; decreased calcitriol receptor FT activity; decreased affinity for calcitriol; decreased FT ligand-independent localization to the nucleus; loss of FT interaction with RXRA; decreased interaction with NCOR1; FT decreased interaction with NCOA1; decreased FT sequence-specific DNA-binding; dbSNP:rs267607169)" FT /evidence="ECO:0000269|PubMed:17970811, FT ECO:0000269|PubMed:28698609" FT /id="VAR_079326" FT VARIANT 360 FT /note="S -> P (in VDDR2A; loss of calcitriol receptor FT activity; loss of affinity for calcitriol; decreased FT ligand-independent localization to the nucleus; loss of FT interaction with RXRA; loss of interaction with NCOR1; loss FT of interaction with NCOA1; loss of sequence-specific FT DNA-binding)" FT /evidence="ECO:0000269|PubMed:28698609" FT /id="VAR_079327" FT VARIANT 362 FT /note="T -> I (in dbSNP:rs11574115)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029310" FT VARIANT 391 FT /note="R -> C (in VDDR2A; dbSNP:rs121909800)" FT /evidence="ECO:0000269|PubMed:8961271" FT /id="VAR_004667" FT MUTAGEN 47..48 FT /note="FF->AA: Abolishes nuclear export." FT /evidence="ECO:0000269|PubMed:12145331" FT MUTAGEN 61..62 FT /note="PF->AA: Promotes heterodimerization with RXRA; when FT associated with A-75." FT /evidence="ECO:0000269|PubMed:11980721" FT MUTAGEN 75 FT /note="H->A: Promotes heterodimerization with RXRA; when FT associated with A-61 and A-62." FT /evidence="ECO:0000269|PubMed:11980721" FT TURN 25..27 FT /evidence="ECO:0007829|PDB:1KB2" FT STRAND 33..35 FT /evidence="ECO:0007829|PDB:1KB2" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:1KB6" FT HELIX 42..53 FT /evidence="ECO:0007829|PDB:1KB2" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:1KB4" FT TURN 70..75 FT /evidence="ECO:0007829|PDB:1KB2" FT HELIX 77..86 FT /evidence="ECO:0007829|PDB:1KB2" FT HELIX 91..93 FT /evidence="ECO:0007829|PDB:1KB2" FT HELIX 97..107 FT /evidence="ECO:0007829|PDB:1KB2" FT STRAND 108..110 FT /evidence="ECO:0007829|PDB:1KB6" FT TURN 111..113 FT /evidence="ECO:0007829|PDB:1KB6" FT HELIX 115..119 FT /evidence="ECO:0007829|PDB:1KB6" FT HELIX 126..142 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:3B0T" FT TURN 162..164 FT /evidence="ECO:0007829|PDB:5V39" FT HELIX 217..223 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 227..247 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 251..253 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 256..274 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:3B0T" FT TURN 281..284 FT /evidence="ECO:0007829|PDB:3B0T" FT STRAND 285..287 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 291..293 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 297..301 FT /evidence="ECO:0007829|PDB:3B0T" FT TURN 302..304 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 307..321 FT /evidence="ECO:0007829|PDB:3B0T" FT TURN 322..324 FT /evidence="ECO:0007829|PDB:2HAR" FT HELIX 327..338 FT /evidence="ECO:0007829|PDB:3B0T" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:3AUQ" FT HELIX 349..370 FT /evidence="ECO:0007829|PDB:3B0T" FT TURN 373..378 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 379..404 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 410..413 FT /evidence="ECO:0007829|PDB:3B0T" FT HELIX 416..422 FT /evidence="ECO:0007829|PDB:3B0T" SQ SEQUENCE 427 AA; 48289 MW; F95F300D042C4CB7 CRC64; MEAMAASTSL PDPGDFDRNV PRICGVCGDR ATGFHFNAMT CEGCKGFFRR SMKRKALFTC PFNGDCRITK DNRRHCQACR LKRCVDIGMM KEFILTDEEV QRKREMILKR KEEEALKDSL RPKLSEEQQR IIAILLDAHH KTYDPTYSDF CQFRPPVRVN DGGGSHPSRP NSRHTPSFSG DSSSSCSDHC ITSSDMMDSS SFSNLDLSEE DSDDPSVTLE LSQLSMLPHL ADLVSYSIQK VIGFAKMIPG FRDLTSEDQI VLLKSSAIEV IMLRSNESFT MDDMSWTCGN QDYKYRVSDV TKAGHSLELI EPLIKFQVGL KKLNLHEEEH VLLMAICIVS PDRPGVQDAA LIEAIQDRLS NTLQTYIRCR HPPPGSHLLY AKMIQKLADL RSLNEEHSKQ YRCLSFQPEC SMKLTPLVLE VFGNEIS //