Nuclear receptor subfamily 1 group I member 2
Details
- Name
- Nuclear receptor subfamily 1 group I member 2
- Synonyms
- Orphan nuclear receptor PAR1
- Orphan nuclear receptor PXR
- Pregnane X receptor
- PXR
- Steroid and xenobiotic receptor
- SXR
- Gene Name
- NR1I2
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0001903|Nuclear receptor subfamily 1 group I member 2 MEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEG CKGFFRRAMKRNARLRCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEE RRALIKRKKSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSS GCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLL PHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHR VVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPF ATPLMQELFGITGS
- Number of residues
- 434
- Molecular Weight
- 49761.245
- Theoretical pI
- 8.44
- GO Classification
- Functionsdrug binding / RNA polymerase II regulatory region sequence-specific DNA binding / RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding / steroid hormone receptor activity / transcription coactivator activity / transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding / zinc ion bindingProcessesdrug export / exogenous drug catabolic process / gene expression / intracellular receptor signaling pathway / negative regulation of transcription, DNA-templated / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / signal transduction / steroid metabolic process / transcription initiation from RNA polymerase II promoter / xenobiotic metabolic process / xenobiotic transportComponentsnucleoplasm
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Nucleus
- Gene sequence
>lcl|BSEQ0010672|Nuclear receptor subfamily 1 group I member 2 (NR1I2) CTGGAGGTGAGACCCAAAGAAAGCTGGAACCATGCTGACTTTGTACACTGTGAGGACACA GAGTCTGTTCCTGGAAAGCCCAGTGTCAACGCAGATGAGGAAGTCGGAGGTCCCCAAATC TGCCGTGTATGTGGGGACAAGGCCACTGGCTATCACTTCAATGTCATGACATGTGAAGGA TGCAAGGGCTTTTTCAGGAGGGCCATGAAACGCAACGCCCGGCTGAGGTGCCCCTTCCGG AAGGGCGCCTGCGAGATCACCCGGAAGACCCGGCGACAGTGCCAGGCCTGCCGCCTGCGC AAGTGCCTGGAGAGCGGCATGAAGAAGGAGATGATCATGTCCGACGAGGCCGTGGAGGAG AGGCGGGCCTTGATCAAGCGGAAGAAAAGTGAACGGACAGGGACTCAGCCACTGGGAGTG CAGGGGCTGACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAA ACCTTTGACACTACCTTCTCCCATTTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGT GGCTGCGAGTTGCCAGAGTCTCTGCAGGCCCCATCGAGGGAAGAAGCTGCCAAGTGGAGC CAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTGCGGGGGGAGGATGGC AGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTG CCCCACATGGCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTC ATCTCCTACTTCAGGGACTTGCCCATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCT TTCGAGCTGTGTCAACTGAGATTCAACACAGTGTTCAACGCGGAGACTGGAACCTGGGAG TGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTCCAGCAACTTCTACTG GAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTAT GTGCTGATGCAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGC GTGGTGGACCAGCTGCAGGAGCAATTCGCCATTACTCTGAAGTCCTACATTGAATGCAAT CGGCCCCAGCCTGCTCATAGGTTCTTGTTCCTGAAGATCATGGCTATGCTCACCGAGCTC CGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAGGACATACACCCCTTT GCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCTGA
- Chromosome Location
- 3
- Locus
- 3q12-q13.3
- External Identifiers
Resource Link UniProtKB ID O75469 UniProtKB Entry Name NR1I2_HUMAN GenBank Protein ID 3511138 GenBank Gene ID AF061056 GenAtlas ID NR1I2 HGNC ID HGNC:7968 - General References
- Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, Evans RM: SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998 Oct 15;12(20):3195-205. [Article]
- Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998 Sep 1;102(5):1016-23. [Article]
- Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A: Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12208-13. [Article]
- Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR Jr, Schuetz EG, Boguski MS: The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001 Oct;11(7):555-72. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. [Article]
- Kawana K, Ikuta T, Kobayashi Y, Gotoh O, Takeda K, Kawajiri K: Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR. Mol Pharmacol. 2003 Mar;63(3):524-31. [Article]
- Li Y, Ross-Viola JS, Shay NF, Moore DD, Ricketts ML: Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via the pregnane X receptor in a species-specific manner. J Nutr. 2009 May;139(5):898-904. doi: 10.3945/jn.108.103572. Epub 2009 Mar 18. [Article]
- Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR: The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science. 2001 Jun 22;292(5525):2329-33. Epub 2001 Jun 14. [Article]
- Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Lambert MH, Kliewer SA, Redinbo MR: 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry. 2003 Feb 18;42(6):1430-8. [Article]
- Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR: Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol. 2003 Aug 22;331(4):815-28. [Article]
- Chrencik JE, Orans J, Moore LB, Xue Y, Peng L, Collins JL, Wisely GB, Lambert MH, Kliewer SA, Redinbo MR: Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin. Mol Endocrinol. 2005 May;19(5):1125-34. Epub 2005 Feb 10. [Article]
- Xue Y, Chao E, Zuercher WJ, Willson TM, Collins JL, Redinbo MR: Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism. Bioorg Med Chem. 2007 Mar 1;15(5):2156-66. Epub 2006 Dec 20. [Article]
- Teotico DG, Bischof JJ, Peng L, Kliewer SA, Redinbo MR: Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Mol Pharmacol. 2008 Dec;74(6):1512-20. doi: 10.1124/mol.108.050732. Epub 2008 Sep 2. [Article]
- Koyano S, Kurose K, Ozawa S, Saeki M, Nakajima Y, Hasegawa R, Komamura K, Ueno K, Kamakura S, Nakajima T, Saito H, Kimura H, Goto Y, Saitoh O, Katoh M, Ohnuma T, Kawai M, Sugai K, Ohtsuki T, Suzuki C, Minami N, Saito Y, Sawada J: Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations. Drug Metab Pharmacokinet. 2002;17(6):561-5. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00783 Estradiol approved, investigational, vet_approved unknown binder Details DB00977 Ethinylestradiol approved unknown agonist Details DB01892 Hyperforin nutraceutical unknown Details DB04466 SR12813 experimental unknown Details DB00163 Vitamin E approved, nutraceutical, vet_approved unknown Details DB01045 Rifampicin approved unknown agonist Details DB01220 Rifaximin approved, investigational no agonist Details DB07080 TO-901317 experimental unknown Details DB00530 Erlotinib approved, investigational yes agonist Details DB08864 Rilpivirine approved unknown agonist Details DB01229 Paclitaxel approved, vet_approved unknown inducer Details DB01248 Docetaxel approved, investigational unknown binder Details DB01708 Prasterone approved, investigational, nutraceutical unknown activator Details DB11605 Myrrh approved unknown partial agonist Details DB00564 Carbamazepine approved, investigational unknown activator Details DB01138 Sulfinpyrazone approved unknown activator Details DB01174 Phenobarbital approved, investigational unknown activator Details DB00252 Phenytoin approved, vet_approved unknown Details DB00503 Ritonavir approved, investigational unknown activator Details DB00257 Clotrimazole approved, vet_approved unknown activator Details DB00754 Ethotoin approved unknown activator Details DB00532 Mephenytoin approved, investigational, withdrawn unknown activator Details DB00849 Methylphenobarbital approved unknown activator Details DB00312 Pentobarbital approved, investigational, vet_approved unknown activator Details DB13179 Troleandomycin approved unknown activator Details DB04468 Afimoxifene investigational unknown Details DB01234 Dexamethasone approved, investigational, vet_approved unknown agonist Details DB00255 Diethylstilbestrol approved, investigational, withdrawn unknown Details DB01645 Genistein investigational unknown Details DB00431 Lindane approved, withdrawn unknown Details DB00834 Mifepristone approved, investigational unknown Details DB02789 Pregnenolone approved, experimental unknown Details DB00421 Spironolactone approved unknown Details DB08604 Triclosan approved, investigational unknown Details DB00675 Tamoxifen approved unknown Details DB06777 Chenodeoxycholic acid approved unknown Details DB01127 Econazole approved unknown partial agonist Details DB01110 Miconazole approved, investigational, vet_approved unknown partial agonist Details DB00239 Oxiconazole approved unknown partial agonist Details DB01026 Ketoconazole approved, investigational unknown antagonist Details DB00531 Cyclophosphamide approved, investigational unknown Details DB00499 Flutamide approved, investigational unknown Details DB01181 Ifosfamide approved unknown Details DB01393 Bezafibrate approved, investigational unknown partial agonist Details DB01068 Clonazepam approved, illicit unknown partial agonist Details DB01039 Fenofibrate approved unknown partial agonist Details DB00682 Warfarin approved unknown Details DB07931 Hexestrol withdrawn unknown Details DB04824 Phenolphthalein approved, withdrawn unknown Details DB02709 Resveratrol investigational unknown Details DB04930 Permethrin approved, investigational unknown Details DB11087 Pyrethrum extract approved unknown Details DB01115 Nifedipine approved unknown agonist Details DB12582 Piperine investigational unknown Details DB04216 Quercetin experimental, investigational unknown activator Details DB13952 Estradiol acetate approved, investigational, vet_approved unknown Details DB13953 Estradiol benzoate approved, investigational, vet_approved unknown Details DB13954 Estradiol cypionate approved, investigational, vet_approved unknown Details DB13955 Estradiol dienanthate approved, investigational, vet_approved unknown Details DB13956 Estradiol valerate approved, investigational, vet_approved unknown Details DB13873 Fenofibric acid approved unknown partial agonist Details DB14001 alpha-Tocopherol succinate approved, nutraceutical, vet_approved unknown Details DB14002 D-alpha-Tocopherol acetate approved, nutraceutical, vet_approved unknown Details DB05928 Dovitinib investigational unknown suppressor Details DB14649 Dexamethasone acetate approved, investigational, vet_approved unknown agonist Details