AC T04617
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ID T04617
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DT 18.07.2001 (created); mas.
DT 15.04.2009 (updated); sva.
CO Copyright (C), QIAGEN.
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FA PXR-isoform1A
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SY hPAR-1; NR1I2; PAR-1; pregnane X receptor; steroid and xenobiotic receptor; SXR.
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OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
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GE G002750 NR1I2; HGNC: NR1I2.
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CL C0002; CC (rec); 2.1.2.4.2.1.
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SZ 434 AA; 49.7 kDa (cDNA) (calc.).
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SQ LEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEG
SQ CKGFFRRAMKRNARLRCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEE
SQ RRALIKRKKSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSS
SQ GCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLL
SQ PHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE
SQ CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHR
SQ VVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPF
SQ ATPLMQELFGITGS
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SC translated from EMBL #AF084645, first amino acid modified according to [4]
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FT 2 286 
PF00478; IMP dehydrogenase / GMP reductase domai.
FT 38 110 
SM00399; c4gold.
FT 38 114 
PS51030; NUCLEAR_REC_DBD_2.
FT 39 115 
DNA-binding domain [4].
FT 39 115 
PF00105; Zinc finger, C4 type (two domains).
FT 77 97 
zinc finger 2 (C-X6-C-X9-C-X2-C), unusual spacing between first two cysteins (6 instead of 5 residues) [4].
FT 141 161 
helical region H1 [3].
FT 141 434 
ligand-binding domain [4].
FT 166 171 
helical region H2 [3].
FT 239 260 
helical region H3 [3].
FT 245 404 SM00430; holi.
FT 248 428 PF00104; Ligand-binding domain of nuclear hormon.
FT 269 278 helical region H4 [3].
FT 280 290 helical region H5 [3].
FT 308 312 helical region H6 [3].
FT 309 321 flexible loop [2].
FT 321 333 helical region H7 [3].
FT 337 348 helical region H8 [3].
FT 360 380 helical region H9 [3].
FT 389 415 helical region H10 [3].
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SF for DNA binding requires dimerization with RXR-alpha, see T05671;
SF splice variants are known, human SXR T04610, PXR-2 T04641;
SF the crystal structure of LBD in a complex with the drug SR12813 has been presented [2];
SF the ligand-binding cavity consists of 28 aa: 20 aa are hydrophobic, four are polar, and four are charged or potentially charged [2];
SF the flexible loop between aa 309 and 321 allows to bind both small and large ligands, this loop is not conserved between mammalian species [2];
SF structure of the ligand-binding pocket permit binding of the same ligand, SR12813, in three different orientations [2];
SF sequence is very similar to the human SXR T04610 except of exchanges at pos. 215-233 (LRGEDGSVWNYKPPADSGG instead of AAGGGWQCLELQTPSRQWR) [1] [4];
SF like in SXR T04610 N-terminal amino acid seems to be Leucine (coded by cDNA-sequence) [4];
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EX adipose tissue,,,embryo; none; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX adrenal gland (right and left),,,embryo; none; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX blood,basophil granulocyte,Circulatory System & Hematopoietic System,adult; none; Northern blot; RNA (undefined); [4].
EX blood,eosinophil granulocyte,Circulatory System & Hematopoietic System,adult; none; Northern blot; RNA (undefined); [4].
EX blood,lymphocyte,Circulatory System & Hematopoietic System,adult; none; Northern blot; RNA (undefined); [4].
EX blood,monocyte,Circulatory System & Hematopoietic System,adult; none; Northern blot; RNA (undefined); [4].
EX blood,neutrophil granulocyte,Circulatory System & Hematopoietic System,adult; none; Northern blot; RNA (undefined); [4].
EX brain,,,adult; none; Northern blot; RNA (undefined); [4].
EX colon,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX connective tissue,,,embryo; none; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX heart,,,adult; none; Northern blot; RNA (undefined); [4].
EX kidney (right and left),,,adult; none; Northern blot; RNA (undefined); [4].
EX liver,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX lung (right and left),,,adult; none; Northern blot; RNA (undefined); [4].
EX mucosa of large intestine,,,embryo; detectable; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX mucosa of small intestine,,,embryo; detectable; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX muscles,,,adult; none; Northern blot; RNA (undefined); [4].
EX muscles,,,embryo; none; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX ovary (right and left),,,adult; none; Northern blot; RNA (undefined); [4].
EX pancreas,,,adult; none; Northern blot; RNA (undefined); [4].
EX placenta,,,adult; none; Northern blot; RNA (undefined); [4].
EX prostate gland,,,adult; none; Northern blot; RNA (undefined); [4].
EX skin,,,embryo; none; RNA-in situ hybridization (not further specified); RNA (undefined); [4].
EX small intestine,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX spleen,,,adult; none; Northern blot; RNA (undefined); [4].
EX testis (right and left),,,adult; none; Northern blot; RNA (undefined); [4].
EX thymus,,,adult; none; Northern blot; RNA (undefined); [4].
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FF activator as a heterodimer with RXR-alpha;
FF regulator of the physiological response to xenobiotics in a complex cross-talk with CAR (NR1I3) [8] [10];
FF regulates physiological response to LCA (toxic bile acid) possibly in the cooperation with FXR (NR1H4), for review, see [11];
FF involved in the coordinated induction of CYP3A4, CYP2C8 and OATP2 in liver and MDR1 in intestine;
FF unprecedented broad range of ligands among nuclear receptor superfamily [3];
FF activating ligands: pregnenolone and its derivates (5beta-pregnane-3,20-dione is most potent activator), steroids (progesterone, 17alpha-hydroxy-pregnenolone, cortisol, 17beta-estradiol), rifampicin, clotrimazole [3] [4];
FF strong activating ligand: bisphosphonate ester SR12813 [3];
FF ligand spectrum different from rodent (rabbit, mouse, rat) orthologs, for example is not activated in the presence of 16alpha-carbonitrile in contrast to mouse ortholog T04618 [4];
FF rifampicin, SR12813, TCPOBOP, phenobarbital are activating ligands for the human PXR-isoform1A, but have no or little effect on the mouse orthologue [8];
FF RU486, clotrimazole, androstanol, 5beta-pregnane-3,20-dione activate both human and mouse PXR-isoform1A [8];
FF xenobiotic TCPOBOP is activator of the human PXR-isoform1A and mouse CAR, but has no effect on the human CAR [8];
FF hyperforin, a drug with antidepressant activity, is a potent activating ligand of the human PXR-isoform1A and activator of the CYP3A4 expression [9];
FF controls bilirubin conjugation and clearance by direct regulation of UGT1A1 [12];
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IN T04689 SMRT; human, Homo sapiens.
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MX M00966 V$DR3_Q4.
MX M00965 V$DR4_Q2.
MX M07280 V$NR1NR2_Q3.
MX M00964 V$PXR_Q2.
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BS R14201.
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DR TRANSPATH: MO000028450.
DR EMBL: AF061056;
DR EMBL: AF084645;
DR EMBL: AF364606; AF364606.
DR UniProtKB: O75469-1;
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RN [1]; RE0016451.
RX PUBMED: 9784494.
RA Blumberg B., Sabbagh W J. r., Juguilon H., Bolado J J. r., van Meter C. M., 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]; RE0016461.
RX PUBMED: 11408620.
RA Watkins R. E., Wisely G. B., Moore L. B., Collins J. L., Lambert M. H., Williams S. P., Willson T. M., Kliewer S. A., Redinbo M. R.
RT The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity
RL Science 292:2329-2333 (2001).
RN [3]; RE0016488.
RX PUBMED: 10628745.
RA Jones S. A., Moore L. B., Shenk J. L., Wisely G. B., Hamilton G. A., McKee D. D., Tomkinson N. C., LeCluyse E. L., Lambert M. H., Willson T. M., Kliewer S. A., Moore J. T.
RT The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution
RL Mol. Endocrinol. 14:27-39 (2000).
RN [4]; RE0016501.
RX PUBMED: 9770465.
RA Bertilsson G., Heidrich J., Svensson K., Asman M., Jendeberg L., Sydow-Backman M., Ohlsson R., Postlind H., Blomquist P., Berkenstam A.
RT Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction
RL Proc. Natl. Acad. Sci. USA 95:12208-12213 (1998).
RN [5]; RE0016510.
RX PUBMED: 10415106.
RA Zhang H., LeCulyse E., Liu L., Hu M., Matoney L., Zhu W., Yan B.
RT Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation
RL Arch. Biochem. Biophys. 368:14-22 (1999).
RN [6]; RE0023222.
RX PUBMED: 11668216.
RA Zhang J., Kuehl P., Green E. D., Touchman J. W., Watkins P. B., Daly A., Hall S. D., Maurel P., Relling M., Brimer C., Yasuda K., Wrighton S. A., Hancock M., Kim R. B., Strom S., Thummel K., Russell C. G., Hudson JR J. r., Schuetz E. G., Boguski M. S.
RT The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants.
RL Pharmacogenetics 11:555-572 (2001).
RN [7]; RE0023228.
RX PUBMED: 9727070.
RA Lehmann J. M., McKee D. D., Watson M. A., Willson T. M., Moore J. T., Kliewer S. A.
RT The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.
RL J. Clin. Invest. 102:1016-1023 (1998).
RN [8]; RE0023233.
RX PUBMED: 10748001.
RA Moore L. B., Parks D. J., Jones S. A., Bledsoe R. K., Consler T. G., Stimmel J. B., Goodwin B., Liddle C., Blanchard S. G., Willson T. M., Collins J. L., Kliewer S. A.
RT Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands.
RL J. Biol. Chem. 275:15122-15127 (2000).
RN [9]; RE0023234.
RX PUBMED: 10852961.
RA Moore L. B., Goodwin B., Jones S. A., Wisely G. B., Serabjit-Singh C. J., Willson T. M., Collins J. L., Kliewer S. A.
RT St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.
RL Proc. Natl. Acad. Sci. USA 97:7500-7502 (2000).
RN [10]; RE0023235.
RX PUBMED: 11502872.
RA Goodwin B., Moore L. B., Stoltz C. M., McKee D. D., Kliewer S. A.
RT Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor.
RL Mol. Pharmacol. 60:427-431 (2001).
RN [11]; RE0023249.
RX PUBMED: 11893771.
RA Kliewer S. A., Willson T. M.
RT Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor.
RL J. Lipid Res. 43:359-364 (2002).
RN [12]; RE0023317.
RX PUBMED: 12644700.
RA Xie W., Yeuh M. F., Radominska-Pandya A., Saini S. P., Negishi Y., Bottroff B. S., Cabrera G. Y., Tukey R. H., Evans R. M.
RT Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor.
RL Proc. Natl. Acad. Sci. USA 100:4150-4155 (2003).
RN [13]; RE0048421.
RX PUBMED: 16219912.
RA Johnson D. R., Li C. W., Chen L. Y., Ghosh J. C., Chen J. D.
RT Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT).
RL Mol. Pharmacol. 69:99-108 (2006).
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