Nuclear receptor subfamily 1 group I member 2

Details

Name
Nuclear receptor subfamily 1 group I member 2
Kind
protein
Synonyms
  • Orphan nuclear receptor PAR1
  • Orphan nuclear receptor PXR
  • Pregnane X receptor
  • PXR
  • Steroid and xenobiotic receptor
  • SXR
Gene Name
NR1I2
UniProtKB Entry
O75469Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
zinc ion binding
Processes
signal transduction / steroid metabolic process / xenobiotic metabolic process / xenobiotic transport
Components
nucleoplasm
General 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
Specific Function
Dna-binding transcription activator activity, rna polymerase ii-specific
Pfam Domain Function
Signal Regions
Not Available
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
3q13.33
External Identifiers
ResourceLink
UniProtKB IDO75469
UniProtKB Entry NameNR1I2_HUMAN
GenBank Protein ID3511138
GenBank Gene IDAF061056
GeneCard IDNR1I2
GenAtlas IDNR1I2
HGNC IDHGNC:7968
PDB ID(s)1ILG, 1ILH, 1M13, 1NRL, 1SKX, 2O9I, 2QNV, 3CTB, 3HVL, 3R8D, 4J5W, 4J5X, 4NY9, 4S0S, 4S0T, 4X1F, 4X1G, 4XAO, 4XHD, 5A86, 5X0R, 6BNS, 6DUP, 6HJ2, 6HTY, 6NX1, 6P2B, 6S41, 6TFI, 6XP9, 7AX8, 7AX9, 7AXA, 7AXB, 7AXC, 7AXD, 7AXE, 7AXF, 7AXG, 7AXH, 7AXI, 7AXJ, 7AXK, 7AXL, 7N2A, 7RIO, 7RIU, 7RIV, 7YFK, 8CCT, 8CF9, 8CH8, 8E3N, 8EQZ, 8F5Y, 8FPE, 8SZV
KEGG IDhsa:8856
IUPHAR/Guide To Pharmacology ID606
NCBI Gene ID8856
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Estradiolapproved, investigational, vet_approvedunknowntargetbinderDetails
EthinylestradiolapprovedunknowntargetagonistDetails
HyperforinnutraceuticalunknowntargetDetails
SR12813experimentalunknowntargetDetails
Vitamin Eapproved, nutraceutical, vet_approvedunknowntargetDetails
RifampinapprovedunknowntargetagonistDetails
Rifaximinapproved, investigationalnotargetagonistDetails
TO-901317experimentalunknowntargetDetails
Erlotinibapproved, investigationalyestargetagonistDetails
RilpivirineapprovedunknowntargetagonistDetails
Paclitaxelapproved, vet_approvedunknowntargetinducerDetails
Docetaxelapproved, investigationalunknowntargetbinderDetails
Prasteroneapproved, investigational, nutraceuticalunknowntargetactivatorDetails
Myrrhapprovedunknowntargetpartial agonistDetails
Carbamazepineapproved, investigationalunknowntargetactivatorDetails
SulfinpyrazoneapprovedunknowntargetactivatorDetails
Phenobarbitalapproved, investigationalunknowntargetactivatorDetails
Phenytoinapproved, vet_approvedunknowntargetDetails
Ritonavirapproved, investigationalunknowntargetactivatorDetails
Clotrimazoleapproved, vet_approvedunknowntargetactivatorDetails
EthotoinapprovedunknowntargetactivatorDetails
Mephenytoinapproved, investigational, withdrawnunknowntargetactivatorDetails
MethylphenobarbitalapprovedunknowntargetactivatorDetails
Pentobarbitalapproved, investigational, vet_approvedunknowntargetactivatorDetails
TroleandomycinapprovedunknowntargetactivatorDetails
AfimoxifeneinvestigationalunknowntargetDetails
Dexamethasoneapproved, investigational, vet_approvedunknowntargetagonistDetails
Diethylstilbestrolapproved, investigational, withdrawnunknowntargetDetails
GenisteininvestigationalunknowntargetDetails
Lindaneapproved, withdrawnunknowntargetDetails
Mifepristoneapproved, investigationalunknowntargetDetails
Pregnenoloneapproved, experimentalunknowntargetDetails
SpironolactoneapprovedunknowntargetagonistDetails
Triclosanapproved, investigationalunknowntargetDetails
TamoxifenapprovedunknowntargetDetails
Chenodeoxycholic acidapprovedunknowntargetDetails
Econazoleapprovedunknowntargetpartial agonistDetails
Miconazoleapproved, investigational, vet_approvedunknowntargetpartial agonistDetails
Oxiconazoleapprovedunknowntargetpartial agonistDetails
Ketoconazoleapproved, investigationalunknowntargetantagonistDetails
Cyclophosphamideapproved, investigationalunknowntargetDetails
Flutamideapproved, investigationalunknowntargetDetails
IfosfamideapprovedunknowntargetDetails
Bezafibrateapproved, investigationalunknowntargetpartial agonistDetails
Clonazepamapproved, illicitunknowntargetpartial agonistDetails
Fenofibrateapprovedunknowntargetpartial agonistDetails
WarfarinapprovedunknowntargetDetails
HexestrolwithdrawnunknowntargetDetails
Phenolphthaleinapproved, withdrawnunknowntargetDetails
ResveratrolinvestigationalunknowntargetDetails
Permethrinapproved, investigationalunknowntargetDetails
Pyrethrum extractapprovedunknowntargetDetails
NifedipineapprovedunknowntargetagonistDetails
PiperineinvestigationalunknowntargetDetails
Quercetinexperimental, investigationalunknowntargetactivatorDetails
Estradiol acetateapproved, investigational, vet_approvedunknowntargetDetails
Estradiol benzoateapproved, investigational, vet_approvedunknowntargetDetails
Estradiol cypionateapproved, investigational, vet_approvedunknowntargetDetails
Estradiol dienanthateapproved, investigational, vet_approvedunknowntargetDetails
Estradiol valerateapproved, investigational, vet_approvedunknowntargetDetails
Fenofibric acidapprovedunknowntargetpartial agonistDetails
alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknowntargetDetails
D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknowntargetDetails
DovitinibinvestigationalunknowntargetsuppressorDetails
Dexamethasone acetateapproved, investigational, vet_approvedunknowntargetagonistDetails