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
Functions
drug 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 binding
Processes
drug 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 transport
Components
nucleoplasm
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
ResourceLink
UniProtKB IDO75469
UniProtKB Entry NameNR1I2_HUMAN
GenBank Protein ID3511138
GenBank Gene IDAF061056
GenAtlas IDNR1I2
HGNC IDHGNC:7968
General References
  1. 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. [PubMed:9784494]
  2. 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. [PubMed:9727070]
  3. 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. [PubMed:9770465]
  4. 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. [PubMed:11668216]
  5. 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. [PubMed:15489334]
  6. 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. [PubMed:11297522]
  7. 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. [PubMed:12606758]
  8. 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. [PubMed:19297428]
  9. 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. [PubMed:11408620]
  10. 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. [PubMed:12578355]
  11. 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. [PubMed:12909012]
  12. 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. [PubMed:15705662]
  13. 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. [PubMed:17215127]
  14. 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. [PubMed:18768384]
  15. 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. [PubMed:15618712]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00783Estradiolapproved, investigational, vet_approvedunknownDetails
DB00977EthinylestradiolapprovedunknownagonistDetails
DB01892HyperforinnutraceuticalunknownDetails
DB04466SR12813experimentalunknownDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknownDetails
DB01045RifampicinapprovedunknownagonistDetails
DB01220Rifaximinapproved, investigationalnoagonistDetails
DB07080N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDEexperimentalunknownDetails
DB00530Erlotinibapproved, investigationalyesagonistDetails
DB08864RilpivirineapprovedunknownagonistDetails
DB01229Paclitaxelapproved, vet_approvedunknowninducerDetails
DB01248Docetaxelapproved, investigationalunknownbinderDetails
DB01708Prasteroneapproved, investigational, nutraceuticalunknownactivatorDetails
DB11605Myrrhapprovedunknownpartial agonistDetails
DB00564Carbamazepineapproved, investigationalunknownDetails
DB01138SulfinpyrazoneapprovedunknownactivatorDetails
DB01174Phenobarbitalapproved, investigationalunknownactivatorDetails
DB00252Phenytoinapproved, vet_approvedunknownDetails
DB00503Ritonavirapproved, investigationalunknownactivatorDetails
DB00257Clotrimazoleapproved, vet_approvedunknownactivatorDetails
DB00754EthotoinapprovedunknownactivatorDetails
DB00532Mephenytoinapproved, investigational, withdrawnunknownactivatorDetails
DB00849MethylphenobarbitalapprovedunknownactivatorDetails
DB00312Pentobarbitalapproved, investigational, vet_approvedunknownactivatorDetails
DB13179TroleandomycinapprovedunknownactivatorDetails
DB04468AfimoxifeneinvestigationalunknownDetails
DB01234Dexamethasoneapproved, investigational, vet_approvedunknownDetails
DB00255Diethylstilbestrolapproved, investigationalunknownDetails
DB01645GenisteininvestigationalunknownDetails
DB00431Lindaneapproved, withdrawnunknownDetails
DB00834Mifepristoneapproved, investigationalunknownDetails
DB02789Pregnenoloneapproved, experimentalunknownDetails
DB00421SpironolactoneapprovedunknownDetails
DB08604Triclosanapproved, investigationalunknownDetails
DB00675TamoxifenapprovedunknownDetails
DB06777Chenodeoxycholic acidapprovedunknownDetails
DB01127Econazoleapprovedunknownpartial agonistDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknownpartial agonistDetails
DB00239Oxiconazoleapprovedunknownpartial agonistDetails
DB01026Ketoconazoleapproved, investigationalunknownantagonistDetails
DB00531Cyclophosphamideapproved, investigationalunknownDetails
DB00499Flutamideapproved, investigationalunknownDetails
DB01181IfosfamideapprovedunknownDetails
DB01393Bezafibrateapproved, investigationalunknownpartial agonistDetails
DB01068Clonazepamapproved, illicitunknownpartial agonistDetails
DB01039Fenofibrateapprovedunknownpartial agonistDetails
DB00682WarfarinapprovedunknownDetails
DB07931HexestrolwithdrawnunknownDetails
DB04824Phenolphthaleinapproved, withdrawnunknownDetails
DB02709Resveratrolapproved, experimental, investigationalunknownDetails
DB04930Permethrinapproved, investigationalunknownDetails
DB11087Pyrethrum extractapprovedunknownDetails
DB01115NifedipineapprovedunknownDetails
DB12582PiperineinvestigationalunknownDetails
DB04216Quercetinexperimental, investigationalunknownactivatorDetails
DB13952Estradiol acetateapproved, investigational, vet_approvedunknownDetails
DB13953Estradiol benzoateapproved, investigational, vet_approvedunknownDetails
DB13954Estradiol cypionateapproved, investigational, vet_approvedunknownDetails
DB13955Estradiol dienanthateapproved, investigational, vet_approvedunknownDetails
DB13956Estradiol valerateapproved, investigational, vet_approvedunknownDetails
DB13873Fenofibric acidapprovedunknownpartial agonistDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknownDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknownDetails
DB05928DovitinibinvestigationalunknownsuppressorDetails