Nuclear receptor subfamily 1 group I member 2

NameNuclear receptor subfamily 1 group I member 2
SynonymsOrphan nuclear receptor PAR1 Orphan nuclear receptor PXR Pregnane X receptor PXR Steroid and xenobiotic receptor SXR
Gene NameNR1I2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001903|Nuclear receptor subfamily 1 group I member 2
MEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEG
CKGFFRRAMKRNARLRCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEE
RRALIKRKKSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSS
GCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLL
PHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE
CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHR
VVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPF
ATPLMQELFGITGS
Number of residues434
Molecular Weight49761.245
Theoretical pI8.44
GO Classification
Functions
    drug binding
zinc ion binding
RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
steroid hormone receptor activity
transcription coactivator activity
RNA polymerase II regulatory region sequence-specific DNA binding
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
Processes
    positive regulation of transcription, DNA-templated
xenobiotic transport
steroid metabolic process
positive regulation of transcription from RNA polymerase II promoter
xenobiotic metabolic process
intracellular receptor signaling pathway
signal transduction
negative regulation of transcription, DNA-templated
gene expression
transcription initiation from RNA polymerase II promoter
drug export
exogenous drug catabolic process
Components
    nucleoplasm
General FunctionZinc ion binding
Specific FunctionNuclear 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.
Transmembrane Regions
GenBank Protein ID3511138
UniProtKB IDO75469
UniProtKB Entry NameNR1I2_HUMAN
Cellular LocationNucleus
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
GenBank Gene IDAF061056
GeneCard IDNone
GenAtlas IDNR1I2
HGNC IDHGNC:7968
Chromosome Location3
Locus3q12-q13.3
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.[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.[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.[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.[11668216 ]
  5. 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.[11297522 ]
  6. 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.[12606758 ]
  7. 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.[19297428 ]
  8. 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.[11408620 ]
  9. 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.[12578355 ]
  10. 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.[12909012 ]
  11. 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.[15705662 ]
  12. 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.[17215127 ]
  13. 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.[18768384 ]
  14. 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.[15618712 ]
  15. 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.[15489334 ]

Related FRC

FRCD ID Name Exact Mass Structure




F11807



alpha-Ionone


192.302




F05634



Fenpropimorph


303.49




F03315



Methoxychlor


345.644




F03343



Ethion


384.5




F03460



Pyrene


202.256




F03701



2,2',4,4',5,5'-Hexachlorobiphenyl


360.864




F03889



Imidacloprid


255.662




F03900



Alachlor


269.769




F04032



Thiobencarb


257.776




F04043



Resmethrin


338.447




F04051



Deltamethrin


505.206




F04050



Cypermethrin


416.298




F04047



Cyfluthrin


434.288




F04053



Fenvalerate


419.905




F04084



Butachlor


311.85




F04333



Chlorothalonil


265.902




F04384



Permethrin


391.288




F04743



Clotrimazole


344.842




F04846



Fenthion


278.321




F05034



Boscalid


343.207




F05822



Buprofezin


305.44




F05037



Captan


300.578




F05064



Etoxazole


359.417




F05060



Dimethenamid


275.791




F05071



Fluazinam


465.089




F05079



Flutolanil


323.315




F05085



Enilconazole


297.179




F05095



Malathion


330.35




F05104



Methoxyfenozide


368.477




F05111



Myclobutanil


288.779




F05115



Oxadiazon


345.22




F05118



Penoxsulam


483.37




F05121



Phosalone


367.799




F05124



Prometryn


241.357




F05127



Propiconazole


342.22




F05130



Pyraclostrobin


387.82




F05139



Tebufenozide


352.478




F05141



Tebupirimfos


318.372




F05148



Triasulfuron


401.822




F05150



Trichlorfon


257.43




F05187



Paclitaxel


853.918




F05289



O-Toluidine


107.156




F05401



Cyazofamid


324.783




F05410



Dithiopyr


401.41




F05417



Fenbuconazole


336.823




F05418



Fludioxonil


248.189




F05425



Isazofos


313.737




F05433



Prallethrin


300.398




F05439



Quintozene


295.321




F05445



Thiram


240.416




F05493



Ethinyl Estradiol


296.41




F05503



N-Decane


142.286




F05513



Simvastatin


418.574




F05523



Farnesol


222.372




F05530



Forskolin


410.507




F05565



2,6-Dimethylphenol


122.167




F05629



Allantoin


158.117




F05631



Tridemorph


297.527




F03276



Clofenotane


354.476




F03281



Dieldrin


380.895




F03283



Chlordane


409.758




F03294



Heptachlor


373.3




F03300



Endrin


380.895




F03303



Pentachlorophenol


266.323




F03370



Chlorpyrifos


350.575




F03381



Chlordecone


490.609




F03386



Dicofol


370.475




F03387



Parathion


291.258




F03437



2,4,5-Trichlorophenol


197.439




F03757



Chlorbenzylate


325.185




F03650



2,2',4,5,5'-Pentachlorobiphenyl


326.422




F03667



2,3',4,4',5-Pentachlorobiphenyl


326.422




F03686



2,2',3,4,4',5'-Hexachlorobiphenyl


360.864




F03774



Bisphenol A


228.291




F03890



Fipronil


437.141




F03901



Acetochlor


269.769




F03929



Pendimethalin


281.312




F04040



Allethrin


302.414




F04042



Phenothrin


350.458




F04044



Tetramethrin


331.412




F04048



Cyhalothrin


449.854




F04085



(±)-Metalaxyl


279.336




F04086



Metolachlor


283.796




F04158



Hydroxytriphenylstannane


367.035




F04380



Fenpropathrin


349.43




F04386



Tralomethrin


665.014




F04719



Warfarin


308.333




F04733



Ergocalciferol


396.659




F04735



Vitamin A


286.459




F04736



Alpha-Tocopherol


430.717




F04776



Ketoconazole


531.434




F04917



(S,E)-Zearalenone


318.369




F05028



Azamethiphos


324.672




F05031



Bensulide


397.503




F05035



Bromacil


261.119




F05036



Butafenacil


474.817




F05043



Cinmethylin


274.404




F05047



Clothianidin


249.673




F05048



Cyanazine


240.695




F11967



Cyhalofop-butyl


357.381




F05053



Dazomet


162.269




F05058



Difenoconazole


406.263




F05062



Ethalfluralin


333.267




F05066



Fenamiphos


303.36




F05067



Fenhexamid


302.195




F05072



Flufenacet


363.331




F05077



Fluroxypyr


255.026




F05078



Flusilazole


315.399




F05080



Folpet


296.546




F05086



Imazamox


305.334




F05089



Indoxacarb


527.837




F05091



Iprodione


330.165




F05092



Isoxaben


332.4




F05103



Methidathion


302.318




F05112



Napropamide


271.36




F05113



Niclosamide


327.117




F05114



Norflurazon


303.669




F05123



Prochloraz


376.662




F05125



Propargite


350.473




F05131



Pyridaben


364.932




F05807



Sethoxydim


327.483




F05138



Sulfentrazone


387.183




F05140



Tebufenpyrad


333.86




F05146



Thiazopyr


396.376




F05151



Triclosan


289.536




F05154



Vinclozolin


286.108




F05164



Genistein


270.24




F05165



Daidzein


254.241




F05168



1-Naphthol


144.173




F05298



Progesterone


314.469




F05319



17-Hydroxyprogesterone


330.468




F05388



Atrazine


215.685




F05391



Butralin


295.339




F05393



Captafol


349.047




F11483



Clodinafop-propargyl


349.742




F05400



Coumaphos


362.761




F05411



Diuron


233.092




F05415



Famoxadone


374.396




F05416



Fenarimol


331.196




F05422



Hexaconazole


314.21




F05426



Linuron


249.091




F05427



Maneb


265.284




F05429



Oryzalin


346.358




F05428



Novaluron


492.706




F05434



Profenofos


373.626




F05446



Triadimefon


293.751




F05447



Triadimenol


295.767




F06003



Triflumizole


345.75




F05450



Trifluralin


335.283




F05451



Triticonazole


317.817




F05452



Zoxamide


336.637




F05482



Estradiol


272.388




F05494



Diethylstilbestrol


268.356




F05495



Estrone


270.372




F05505



Celecoxib


381.373




F05521



2,4,6-Tribromophenol


330.801




F05524



Alpha-Linolenic Acid


278.436




F05525



Masoprocol


302.37




F05538



4-Nonylphenol


220.356




F02904



Geranyl acetate


196.29




F05546



Glutaral


100.117




F05566



2,6-Diethylaniline


149.237




F05571



Ethoxyquin


217.312




F05589



5,7-Dihydroxyflavone


254.241




F05620



Terpinolene


136.238




F05622



Nerolidol


222.372