ID NR1I2_HUMAN Reviewed; 434 AA. AC O75469; Q006P5; Q008C8; Q96AC7; Q9UJ22; Q9UJ23; Q9UJ24; Q9UJ25; Q9UJ26; AC Q9UJ27; Q9UNW4; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 24-JAN-2024, entry version 234. DE RecName: Full=Nuclear receptor subfamily 1 group I member 2; DE AltName: Full=Orphan nuclear receptor PAR1; DE AltName: Full=Orphan nuclear receptor PXR; DE AltName: Full=Pregnane X receptor; DE AltName: Full=Steroid and xenobiotic receptor; DE Short=SXR; GN Name=NR1I2; Synonyms=PXR; 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 1A). RX PubMed=9784494; DOI=10.1101/gad.12.20.3195; RA Blumberg B., Sabbagh W. Jr., Juguilon H., Bolado J. Jr., van Meter C.M., RA Ong E.S., Evans R.M.; RT "SXR, a novel steroid and xenobiotic-sensing nuclear receptor."; RL Genes Dev. 12:3195-3205(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A), AND FUNCTION. RC TISSUE=Liver; RX PubMed=9727070; DOI=10.1172/jci3703; RA Lehmann J.M., McKee D.D., Watson M.A., Willson T.M., Moore J.T., RA Kliewer S.A.; RT "The human orphan nuclear receptor PXR is activated by compounds that RT regulate CYP3A4 gene expression and cause drug interactions."; RL J. Clin. Invest. 102:1016-1023(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 3). RC TISSUE=Liver; RX PubMed=9770465; DOI=10.1073/pnas.95.21.12208; RA Bertilsson G., Heidrich J., Svensson K., Asman M., Jendeberg L., RA Sydow-Baeckman M., Ohlsson R., Postlind H., Blomquist P., Berkenstam A.; RT "Identification of a human nuclear receptor defines a new signaling pathway RT for CYP3A induction."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12208-12213(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1A AND 3), FUNCTION, AND RP VARIANTS SER-27; ARG-36 AND GLN-122. RX PubMed=11668216; DOI=10.1097/00008571-200110000-00003; RA Zhang J., Kuehl P., Green E.D., Touchman J.W., Watkins P.B., Daly A., RA Hall S.D., Maurel P., Relling M., Brimer C., Yasuda K., Wrighton S.A., RA Hancock M., Kim R.B., Strom S., Thummel K., Russell C.G., Hudson J.R. Jr., RA Schuetz E.G., Boguski M.S.; RT "The human pregnane X receptor: genomic structure and identification and RT functional characterization of natural allelic variants."; RL Pharmacogenetics 11:555-572(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A; 1B; 1C; 2A; 2B AND 2C), AND RP VARIANT THR-12. RC TISSUE=Liver; RA Heard D.J., Holloway J., Hansen C., Tommerup N., Aagaard L., Vissing H.; RT "Identification of a novel protein isoform of the human nuclear hormone RT receptor PXR/SXR and localization to chromosome 3q12.1 -13.3."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang X., Li J., Deng X., Chen J., Huang M.; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-18; SER-27 AND THR-370. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A). RC TISSUE=Hepatoma; 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 [9] RP FUNCTION. RX PubMed=11297522; DOI=10.1074/jbc.m010173200; RA Geick A., Eichelbaum M., Burk O.; RT "Nuclear receptor response elements mediate induction of intestinal MDR1 by RT rifampin."; RL J. Biol. Chem. 276:14581-14587(2001). RN [10] RP SUBCELLULAR LOCATION, MUTAGENESIS OF 66-ARG-ARG-67 AND 91-ARG-ARG-92, AND RP NUCLEAR LOCALIZATION SIGNAL. RX PubMed=12606758; DOI=10.1124/mol.63.3.524; RA Kawana K., Ikuta T., Kobayashi Y., Gotoh O., Takeda K., Kawajiri K.; RT "Molecular mechanism of nuclear translocation of an orphan nuclear RT receptor, SXR."; RL Mol. Pharmacol. 63:524-531(2003). RN [11] RP FUNCTION. RX PubMed=19297428; DOI=10.3945/jn.108.103572; RA Li Y., Ross-Viola J.S., Shay N.F., Moore D.D., Ricketts M.L.; RT "Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via RT the pregnane X receptor in a species-specific manner."; RL J. Nutr. 139:898-904(2009). RN [12] {ECO:0007744|PDB:1ILG, ECO:0007744|PDB:1ILH} RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 130-434 IN COMPLEX WITH THE RP CHOLESTEROL-LOWERING COMPOUND SR12813. RX PubMed=11408620; DOI=10.1126/science.1060762; RA Watkins R.E., Wisely G.B., Moore L.B., Collins J.L., Lambert M.H., RA Williams S.P., Willson T.M., Kliewer S.A., Redinbo M.R.; RT "The human nuclear xenobiotic receptor PXR: structural determinants of RT directed promiscuity."; RL Science 292:2329-2333(2001). RN [13] {ECO:0007744|PDB:1M13} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 130-434 IN COMPLEX WITH RP HYPERFORIN, FUNCTION, AND INTERACTION WITH NCOA1. RX PubMed=12578355; DOI=10.1021/bi0268753; RA Watkins R.E., Maglich J.M., Moore L.B., Wisely G.B., Noble S.M., RA Davis-Searles P.R., Lambert M.H., Kliewer S.A., Redinbo M.R.; RT "2.1 A crystal structure of human PXR in complex with the St. John's wort RT compound hyperforin."; RL Biochemistry 42:1430-1438(2003). RN [14] {ECO:0007744|PDB:1NRL} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 130-434 IN COMPLEX WITH THE RP CHOLESTEROL-LOWERING COMPOUND SR12813 AND NCOA1. RX PubMed=12909012; DOI=10.1016/s0022-2836(03)00795-2; RA Watkins R.E., Davis-Searles P.R., Lambert M.H., Redinbo M.R.; RT "Coactivator binding promotes the specific interaction between ligand and RT the pregnane X receptor."; RL J. Mol. Biol. 331:815-828(2003). RN [15] {ECO:0007744|PDB:1SKX} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 130-431 IN COMPLEX WITH RP RIFAMPICIN. RX PubMed=15705662; DOI=10.1210/me.2004-0346; RA Chrencik J.E., Orans J., Moore L.B., Xue Y., Peng L., Collins J.L., RA Wisely G.B., Lambert M.H., Kliewer S.A., Redinbo M.R.; RT "Structural disorder in the complex of human pregnane X receptor and the RT macrolide antibiotic rifampicin."; RL Mol. Endocrinol. 19:1125-1134(2005). RN [16] {ECO:0007744|PDB:2O9I} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 142-434 IN COMPLEX WITH T0901317 RP AND NCOA1, AND INTERACTION WITH NCOA1. RX PubMed=17215127; DOI=10.1016/j.bmc.2006.12.026; RA Xue Y., Chao E., Zuercher W.J., Willson T.M., Collins J.L., Redinbo M.R.; RT "Crystal structure of the PXR-T1317 complex provides a scaffold to examine RT the potential for receptor antagonism."; RL Bioorg. Med. Chem. 15:2156-2166(2007). RN [17] {ECO:0007744|PDB:2QNV} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 130-434 IN COMPLEX WITH RP COLUPULONE, AND FUNCTION. RX PubMed=18768384; DOI=10.1124/mol.108.050732; RA Teotico D.G., Bischof J.J., Peng L., Kliewer S.A., Redinbo M.R.; RT "Structural basis of human pregnane X receptor activation by the hops RT constituent colupulone."; RL Mol. Pharmacol. 74:1512-1520(2008). RN [18] RP VARIANTS CYS-98; GLN-148; TRP-381 AND VAL-403. RX PubMed=15618712; DOI=10.2133/dmpk.17.561; RA Koyano S., Kurose K., Ozawa S., Saeki M., Nakajima Y., Hasegawa R., RA Komamura K., Ueno K., Kamakura S., Nakajima T., Saito H., Kimura H., RA Goto Y., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K., Ohtsuki T., RA Suzuki C., Minami N., Saito Y., Sawada J.; RT "Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four RT of which induce non-synonymous amino acid alterations."; RL Drug Metab. Pharmacokinet. 17:561-565(2002). CC -!- FUNCTION: Nuclear receptor that binds and is activated by variety of CC endogenous and xenobiotic compounds. Transcription factor that CC activates the transcription of multiple genes involved in the CC metabolism and secretion of potentially harmful xenobiotics, drugs and CC endogenous compounds. Activated by the antibiotic rifampicin and CC various plant metabolites, such as hyperforin, guggulipid, colupulone, CC and isoflavones. Response to specific ligands is species-specific. CC Activated by naturally occurring steroids, such as pregnenolone and CC progesterone. Binds to a response element in the promoters of the CC CYP3A4 and ABCB1/MDR1 genes. {ECO:0000269|PubMed:11297522, CC ECO:0000269|PubMed:11668216, ECO:0000269|PubMed:12578355, CC ECO:0000269|PubMed:18768384, ECO:0000269|PubMed:19297428, CC ECO:0000269|PubMed:9727070}. CC -!- SUBUNIT: Heterodimer with RXR. Interacts with NCOA1. Interacts (via CC domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner (By CC similarity). {ECO:0000250|UniProtKB:O54915, CC ECO:0000269|PubMed:12578355, ECO:0000269|PubMed:12909012, CC ECO:0000269|PubMed:15705662, ECO:0000269|PubMed:17215127, CC ECO:0000269|PubMed:18768384}. CC -!- INTERACTION: CC O75469; P08238: HSP90AB1; NbExp=2; IntAct=EBI-3905991, EBI-352572; CC O75469; Q15788: NCOA1; NbExp=5; IntAct=EBI-3905991, EBI-455189; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, CC ECO:0000269|PubMed:12606758}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1A; Synonyms=1, PRR1-A; CC IsoId=O75469-1; Sequence=Displayed; CC Name=1B; Synonyms=PRR1-B; CC IsoId=O75469-2; Sequence=VSP_003668; CC Name=1C; Synonyms=PRR1-C; CC IsoId=O75469-3; Sequence=VSP_003667; CC Name=2A; Synonyms=2, PRR2-A; CC IsoId=O75469-4; Sequence=VSP_003669; CC Name=2B; Synonyms=PRR2-B; CC IsoId=O75469-5; Sequence=VSP_003668, VSP_003669; CC Name=2C; Synonyms=PRR2-C; CC IsoId=O75469-6; Sequence=VSP_003667, VSP_003669; CC Name=3; CC IsoId=O75469-7; Sequence=VSP_026669; CC -!- TISSUE SPECIFICITY: Expressed in liver, colon and small intestine. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/nr1i2/"; 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; AY091855; AAM26736.1; -; mRNA. DR EMBL; AF061056; AAD05436.1; -; mRNA. DR EMBL; AF084644; AAC64557.1; -; mRNA. DR EMBL; AF084645; AAC64558.1; -; mRNA. DR EMBL; AF364606; AAK38720.1; -; Genomic_DNA. DR EMBL; AF364606; AAK38721.1; -; Genomic_DNA. DR EMBL; AF364606; AAK38722.1; -; Genomic_DNA. DR EMBL; AJ009936; CAB55489.1; -; mRNA. DR EMBL; AJ009936; CAB55490.1; -; mRNA. DR EMBL; AJ009936; CAB55491.1; -; mRNA. DR EMBL; AJ009937; CAB55492.1; -; mRNA. DR EMBL; AJ009937; CAB55493.1; -; mRNA. DR EMBL; AJ009937; CAB55494.1; -; mRNA. DR EMBL; DQ911122; ABJ52965.1; -; Genomic_DNA. DR EMBL; DQ923326; ABJ52966.1; -; Genomic_DNA. DR EMBL; EF614253; ABR09276.1; -; Genomic_DNA. DR EMBL; BC017304; AAH17304.2; -; mRNA. DR CCDS; CCDS2995.1; -. [O75469-7] DR CCDS; CCDS43136.1; -. [O75469-1] DR CCDS; CCDS54627.1; -. [O75469-4] DR RefSeq; NP_003880.3; NM_003889.3. [O75469-1] DR RefSeq; NP_071285.1; NM_022002.2. [O75469-7] DR RefSeq; NP_148934.1; NM_033013.2. [O75469-4] DR PDB; 1ILG; X-ray; 2.52 A; A=130-434. DR PDB; 1ILH; X-ray; 2.76 A; A=130-434. DR PDB; 1M13; X-ray; 2.15 A; A=130-434. DR PDB; 1NRL; X-ray; 2.00 A; A/B=130-434. DR PDB; 1SKX; X-ray; 2.80 A; A=130-431. DR PDB; 2O9I; X-ray; 2.80 A; A/B=142-434. DR PDB; 2QNV; X-ray; 2.80 A; A=130-434. DR PDB; 3CTB; X-ray; 2.00 A; A/B=130-434. DR PDB; 3HVL; X-ray; 2.10 A; A/B=130-434. DR PDB; 3R8D; X-ray; 2.80 A; A=130-434. DR PDB; 4J5W; X-ray; 2.80 A; A/B=130-434. DR PDB; 4J5X; X-ray; 2.80 A; A/B=130-434. DR PDB; 4NY9; X-ray; 2.80 A; A=142-431. DR PDB; 4S0S; X-ray; 2.80 A; A/B=130-434. DR PDB; 4S0T; X-ray; 3.14 A; A/B=130-434. DR PDB; 4X1F; X-ray; 2.00 A; A=130-434. DR PDB; 4X1G; X-ray; 2.25 A; A=130-434. DR PDB; 4XAO; X-ray; 2.58 A; A=130-434. DR PDB; 4XHD; X-ray; 2.40 A; A=130-434. DR PDB; 5A86; X-ray; 2.25 A; A/B=130-432. DR PDB; 5X0R; X-ray; 2.67 A; A/B=130-434. DR PDB; 6BNS; X-ray; 2.56 A; A/B=130-434. DR PDB; 6DUP; X-ray; 2.30 A; A/B=130-426. DR PDB; 6HJ2; X-ray; 2.28 A; A=130-434. DR PDB; 6HTY; X-ray; 2.22 A; A/B=129-434. DR PDB; 6NX1; X-ray; 2.27 A; A/B=130-434. DR PDB; 6P2B; X-ray; 2.30 A; A/B=130-434. DR PDB; 6S41; X-ray; 2.70 A; A/B=138-434. DR PDB; 6TFI; X-ray; 1.85 A; A/B=129-434. DR PDB; 6XP9; X-ray; 2.27 A; A/B=130-434. DR PDB; 7AX8; X-ray; 2.15 A; A=130-434. DR PDB; 7AX9; X-ray; 2.25 A; A=130-434. DR PDB; 7AXA; X-ray; 2.26 A; A=130-434. DR PDB; 7AXB; X-ray; 2.55 A; A=130-434. DR PDB; 7AXC; X-ray; 2.05 A; A=130-434. DR PDB; 7AXD; X-ray; 2.65 A; A=130-434. DR PDB; 7AXE; X-ray; 1.90 A; A=130-434. DR PDB; 7AXF; X-ray; 2.45 A; A=130-434. DR PDB; 7AXG; X-ray; 2.70 A; A=130-434. DR PDB; 7AXH; X-ray; 2.55 A; A=130-434. DR PDB; 7AXI; X-ray; 2.15 A; A=130-434. DR PDB; 7AXJ; X-ray; 2.30 A; A=130-434. DR PDB; 7AXK; X-ray; 2.00 A; A=130-434. DR PDB; 7AXL; X-ray; 2.50 A; A=130-434. DR PDB; 7N2A; X-ray; 2.26 A; A=137-434. DR PDB; 7RIO; X-ray; 2.48 A; A=137-434. DR PDB; 7RIU; X-ray; 2.05 A; A=137-434. DR PDB; 7RIV; X-ray; 2.20 A; A=137-434. DR PDB; 7YFK; X-ray; 2.10 A; A/B=130-434. DR PDB; 8E3N; X-ray; 2.25 A; A=130-434. DR PDB; 8EQZ; X-ray; 2.37 A; A/B=130-434. DR PDB; 8FPE; X-ray; 2.30 A; A=130-434. DR PDB; 8SZV; X-ray; 2.20 A; A=130-434. DR PDBsum; 1ILG; -. DR PDBsum; 1ILH; -. DR PDBsum; 1M13; -. DR PDBsum; 1NRL; -. DR PDBsum; 1SKX; -. DR PDBsum; 2O9I; -. DR PDBsum; 2QNV; -. DR PDBsum; 3CTB; -. DR PDBsum; 3HVL; -. DR PDBsum; 3R8D; -. DR PDBsum; 4J5W; -. DR PDBsum; 4J5X; -. DR PDBsum; 4NY9; -. DR PDBsum; 4S0S; -. DR PDBsum; 4S0T; -. DR PDBsum; 4X1F; -. DR PDBsum; 4X1G; -. DR PDBsum; 4XAO; -. DR PDBsum; 4XHD; -. DR PDBsum; 5A86; -. DR PDBsum; 5X0R; -. DR PDBsum; 6BNS; -. DR PDBsum; 6DUP; -. DR PDBsum; 6HJ2; -. DR PDBsum; 6HTY; -. DR PDBsum; 6NX1; -. DR PDBsum; 6P2B; -. DR PDBsum; 6S41; -. DR PDBsum; 6TFI; -. DR PDBsum; 6XP9; -. DR PDBsum; 7AX8; -. DR PDBsum; 7AX9; -. DR PDBsum; 7AXA; -. DR PDBsum; 7AXB; -. DR PDBsum; 7AXC; -. DR PDBsum; 7AXD; -. DR PDBsum; 7AXE; -. DR PDBsum; 7AXF; -. DR PDBsum; 7AXG; -. DR PDBsum; 7AXH; -. DR PDBsum; 7AXI; -. DR PDBsum; 7AXJ; -. DR PDBsum; 7AXK; -. DR PDBsum; 7AXL; -. DR PDBsum; 7N2A; -. DR PDBsum; 7RIO; -. DR PDBsum; 7RIU; -. DR PDBsum; 7RIV; -. DR PDBsum; 7YFK; -. DR PDBsum; 8E3N; -. DR PDBsum; 8EQZ; -. DR PDBsum; 8FPE; -. DR PDBsum; 8SZV; -. DR AlphaFoldDB; O75469; -. DR SASBDB; O75469; -. DR SMR; O75469; -. DR BioGRID; 114380; 46. DR ComplexPortal; CPX-496; RXRalpha-PXR nuclear receptor complex. DR ComplexPortal; CPX-517; PXR-NCOA1 activated nuclear receptor complex. DR IntAct; O75469; 11. DR STRING; 9606.ENSP00000336528; -. DR BindingDB; O75469; -. DR ChEMBL; CHEMBL3401; -. DR DrugBank; DB04468; Afimoxifene. DR DrugBank; DB14001; alpha-Tocopherol succinate. DR DrugBank; DB01393; Bezafibrate. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB06777; Chenodeoxycholic acid. DR DrugBank; DB01068; Clonazepam. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB14002; D-alpha-Tocopherol acetate. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB01248; Docetaxel. DR DrugBank; DB05928; Dovitinib. DR DrugBank; DB01127; Econazole. DR DrugBank; DB00530; Erlotinib. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB13952; Estradiol acetate. DR DrugBank; DB13953; Estradiol benzoate. DR DrugBank; DB13954; Estradiol cypionate. DR DrugBank; DB13955; Estradiol dienanthate. DR DrugBank; DB13956; Estradiol valerate. DR DrugBank; DB00977; Ethinylestradiol. DR DrugBank; DB00754; Ethotoin. DR DrugBank; DB01039; Fenofibrate. DR DrugBank; DB13873; Fenofibric acid. DR DrugBank; DB00499; Flutamide. DR DrugBank; DB01645; Genistein. DR DrugBank; DB07931; Hexestrol. DR DrugBank; DB01892; Hyperforin. DR DrugBank; DB01181; Ifosfamide. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB00431; Lindane. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB00849; Methylphenobarbital. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB11605; Myrrh. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB00239; Oxiconazole. DR DrugBank; DB01229; Paclitaxel. DR DrugBank; DB00312; Pentobarbital. DR DrugBank; DB04930; Permethrin. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB04824; Phenolphthalein. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB12582; Piperine. DR DrugBank; DB01708; Prasterone. DR DrugBank; DB02789; Pregnenolone. DR DrugBank; DB11087; Pyrethrum extract. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB01220; Rifaximin. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB04466; SR12813. DR DrugBank; DB01138; Sulfinpyrazone. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB07080; TO-901317. DR DrugBank; DB08604; Triclosan. DR DrugBank; DB13179; Troleandomycin. DR DrugBank; DB00163; Vitamin E. DR DrugBank; DB00682; Warfarin. DR DrugCentral; O75469; -. DR GuidetoPHARMACOLOGY; 606; -. DR SwissLipids; SLP:000001583; -. DR TCDB; 9.B.208.1.3; the vitamin d3 receptor (vdr) family. DR iPTMnet; O75469; -. DR PhosphoSitePlus; O75469; -. DR BioMuta; NR1I2; -. DR MassIVE; O75469; -. DR PaxDb; 9606-ENSP00000336528; -. DR PeptideAtlas; O75469; -. DR Antibodypedia; 16619; 482 antibodies from 42 providers. DR DNASU; 8856; -. DR Ensembl; ENST00000337940.4; ENSP00000336528.4; ENSG00000144852.20. [O75469-7] DR Ensembl; ENST00000393716.8; ENSP00000377319.3; ENSG00000144852.20. [O75469-1] DR Ensembl; ENST00000466380.6; ENSP00000420297.2; ENSG00000144852.20. [O75469-4] DR GeneID; 8856; -. DR KEGG; hsa:8856; -. DR MANE-Select; ENST00000393716.8; ENSP00000377319.3; NM_003889.4; NP_003880.3. DR UCSC; uc003edk.3; human. [O75469-1] DR AGR; HGNC:7968; -. DR CTD; 8856; -. DR DisGeNET; 8856; -. DR GeneCards; NR1I2; -. DR HGNC; HGNC:7968; NR1I2. DR HPA; ENSG00000144852; Group enriched (intestine, liver). DR MIM; 603065; gene. DR neXtProt; NX_O75469; -. DR OpenTargets; ENSG00000144852; -. DR PharmGKB; PA378; -. DR VEuPathDB; HostDB:ENSG00000144852; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000161118; -. DR InParanoid; O75469; -. DR OMA; GTCEITQ; -. DR OrthoDB; 5359733at2759; -. DR PhylomeDB; O75469; -. DR TreeFam; TF316304; -. DR PathwayCommons; O75469; -. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. [O75469-1] DR SignaLink; O75469; -. DR SIGNOR; O75469; -. DR BioGRID-ORCS; 8856; 10 hits in 1183 CRISPR screens. DR EvolutionaryTrace; O75469; -. DR GeneWiki; Pregnane_X_receptor; -. DR GenomeRNAi; 8856; -. DR Pharos; O75469; Tchem. DR PRO; PR:O75469; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O75469; Protein. DR Bgee; ENSG00000144852; Expressed in right lobe of liver and 84 other cell types or tissues. DR ExpressionAtlas; O75469; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0016922; F:nuclear receptor binding; IDA:GO_Central. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0008202; P:steroid metabolic process; TAS:ProtInc. DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:UniProtKB. DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB. DR GO; GO:0042908; P:xenobiotic transport; IDA:UniProtKB. DR CDD; cd06934; NR_LBD_PXR_like; 1. DR DisProt; DP00323; -. 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 IDEAL; IID00361; -. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1. DR PANTHER; PTHR24082:SF39; NUCLEAR RECEPTOR SUBFAMILY 1 GROUP I MEMBER 2; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. 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; O75469; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; DNA-binding; Metal-binding; KW Nucleus; Receptor; Reference proteome; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..434 FT /note="Nuclear receptor subfamily 1 group I member 2" FT /id="PRO_0000053547" FT DOMAIN 146..433 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 38..107 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 41..61 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 77..102 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 108..145 FT /note="Hinge" FT MOTIF 66..92 FT /note="Bipartite nuclear localization signal" FT BINDING 247 FT /ligand="hyperforin" FT /ligand_id="ChEBI:CHEBI:5834" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:12578355, FT ECO:0007744|PDB:1M13" FT BINDING 285..288 FT /ligand="hyperforin" FT /ligand_id="ChEBI:CHEBI:5834" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:12578355, FT ECO:0007744|PDB:1M13" FT BINDING 407 FT /ligand="hyperforin" FT /ligand_id="ChEBI:CHEBI:5834" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:12578355, FT ECO:0007744|PDB:1M13" FT VAR_SEQ 1..55 FT /note="Missing (in isoform 1B and isoform 2B)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_003668" FT VAR_SEQ 1 FT /note="M -> MDPRGEVGAKNLPPNSPRGPEANL (in isoform 1C and FT isoform 2C)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_003667" FT VAR_SEQ 1 FT /note="M -> MTVTRTHHFKEGSLRAPAIPLHSAAAELASNHPRGPEANL (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:9770465" FT /id="VSP_026669" FT VAR_SEQ 174..210 FT /note="Missing (in isoform 2A, isoform 2B and isoform 2C)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_003669" FT VARIANT 12 FT /note="A -> T (in dbSNP:rs1063955)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_050581" FT VARIANT 18 FT /note="E -> K (in dbSNP:rs59371185)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_033237" FT VARIANT 27 FT /note="P -> S (in allele PXR*2; dbSNP:rs12721613)" FT /evidence="ECO:0000269|PubMed:11668216, ECO:0000269|Ref.7" FT /id="VAR_012228" FT VARIANT 36 FT /note="G -> R (in allele PXR*3; dbSNP:rs12721607)" FT /evidence="ECO:0000269|PubMed:11668216" FT /id="VAR_012229" FT VARIANT 98 FT /note="R -> C (in dbSNP:rs72551371)" FT /evidence="ECO:0000269|PubMed:15618712" FT /id="VAR_018340" FT VARIANT 122 FT /note="R -> Q (in allele PXR*4; dbSNP:rs12721608)" FT /evidence="ECO:0000269|PubMed:11668216" FT /id="VAR_012230" FT VARIANT 148 FT /note="R -> Q (in dbSNP:rs72551373)" FT /evidence="ECO:0000269|PubMed:15618712" FT /id="VAR_018341" FT VARIANT 370 FT /note="A -> T (in dbSNP:rs35761343)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_033238" FT VARIANT 381 FT /note="R -> W (in dbSNP:rs72551375)" FT /evidence="ECO:0000269|PubMed:15618712" FT /id="VAR_018342" FT VARIANT 403 FT /note="I -> V (in dbSNP:rs72551376)" FT /evidence="ECO:0000269|PubMed:15618712" FT /id="VAR_018343" FT MUTAGEN 66..67 FT /note="RR->AA: Abolishes nuclear localization; when FT associated with 91-A-A-92." FT /evidence="ECO:0000269|PubMed:12606758" FT MUTAGEN 91..92 FT /note="RR->AA: Abolishes nuclear localization; when FT associated with 66-A-A-67." FT /evidence="ECO:0000269|PubMed:12606758" FT CONFLICT 109 FT /note="K -> N (in Ref. 5; FT CAB55489/CAB55490/CAB55491/CAB55492/CAB55493/CAB55494)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="Missing (in Ref. 8; AAH17304)" FT /evidence="ECO:0000305" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 145..161 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 193..207 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 211..216 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:6DUP" FT STRAND 222..226 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:1M13" FT HELIX 234..237 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 240..260 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 262..265 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 269..289 FT /evidence="ECO:0007829|PDB:6TFI" FT TURN 294..297 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 298..301 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 304..308 FT /evidence="ECO:0007829|PDB:6TFI" FT TURN 312..314 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 315..318 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 322..332 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 337..348 FT /evidence="ECO:0007829|PDB:6TFI" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:2QNV" FT HELIX 359..380 FT /evidence="ECO:0007829|PDB:6TFI" FT TURN 383..388 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 389..417 FT /evidence="ECO:0007829|PDB:6TFI" FT HELIX 423..429 FT /evidence="ECO:0007829|PDB:6TFI" SQ SEQUENCE 434 AA; 49762 MW; 1DF6A2AE3109C4DA CRC64; MEVRPKESWN HADFVHCEDT ESVPGKPSVN ADEEVGGPQI CRVCGDKATG YHFNVMTCEG CKGFFRRAMK RNARLRCPFR KGACEITRKT RRQCQACRLR KCLESGMKKE MIMSDEAVEE RRALIKRKKS ERTGTQPLGV QGLTEEQRMM IRELMDAQMK TFDTTFSHFK NFRLPGVLSS GCELPESLQA PSREEAAKWS QVRKDLCSLK VSLQLRGEDG SVWNYKPPAD SGGKEIFSLL PHMADMSTYM FKGIISFAKV ISYFRDLPIE DQISLLKGAA FELCQLRFNT VFNAETGTWE CGRLSYCLED TAGGFQQLLL EPMLKFHYML KKLQLHEEEY VLMQAISLFS PDRPGVLQHR VVDQLQEQFA ITLKSYIECN RPQPAHRFLF LKIMAMLTEL RSINAQHTQR LLRIQDIHPF ATPLMQELFG ITGS //