NR1I2_HUMAN
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 03-AUG-2022, entry version 226.
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/";
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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; 7CHG; X-ray; 1.93 A; A/B=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 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; 7CHG; -.
DR PDBsum; 7N2A; -.
DR PDBsum; 7RIO; -.
DR PDBsum; 7RIU; -.
DR PDBsum; 7RIV; -.
DR AlphaFoldDB; O75469; -.
DR SASBDB; O75469; -.
DR SMR; O75469; -.
DR BioGRID; 114380; 42.
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; O75469; -.
DR PeptideAtlas; O75469; -.
DR PRIDE; O75469; -.
DR ProteomicsDB; 50027; -. [O75469-1]
DR ProteomicsDB; 50028; -. [O75469-2]
DR ProteomicsDB; 50029; -. [O75469-3]
DR ProteomicsDB; 50030; -. [O75469-4]
DR ProteomicsDB; 50031; -. [O75469-5]
DR ProteomicsDB; 50032; -. [O75469-6]
DR ProteomicsDB; 50033; -. [O75469-7]
DR Antibodypedia; 16619; 425 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 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; DEEPKAC; -.
DR OrthoDB; 297114at2759; -.
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 1097 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 tissues.
DR ExpressionAtlas; O75469; baseline and differential.
DR Genevisible; O75469; HS.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; 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 DisProt; DP00323; -.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
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; CAB55489/CAB55490/CAB55491/
FT 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
