AC T04618
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ID T04618
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DT 19.07.2001 (created); mas.
DT 26.06.2009 (updated); mka.
CO Copyright (C), QIAGEN.
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FA PXR-isoform1
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SY NR1I2; pregnane X receptor; PXR.
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OS mouse, Mus musculus
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; rodentia; myomorpha; muridae; murinae
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GE G002752 Nr1i2.
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CL C0002; CC (rec); 2.1.2.4.2.1.
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SZ 431 AA; 49.6 kDa (cDNA) (calc.).
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SQ MRPEESWSRVGLVQCEEADSALEEPINVEEEDGGLQICRVCGDKANGYHFNVMTCEGCKG
SQ FFRRAMKRNVRLRCPFRKGTCEITRKTRRQCQACRLRKCLESGMKKEMIMSDAAVEQRRA
SQ LIKRKKREKIEAPPPGGQGLTEEQQALIQELMDAQMQTFDTTFSHFKDFRLPAVFHSGCE
SQ LPEFLQASLLEDPATWSQIMKDRVPMKISLQLRGEDGSIWNYQPPSKSDGKEIIPLLPHL
SQ ADVSTYMFKGVINFAKVISYFRDLPIEDQISLLKGATFEMCILRFNTMFDTETGTWECGR
SQ LAYCFEDPNGGFQKLLLDPLMKFHCMLKKLQLHKEEYVLMQAISLFSPDRPGVVQRSVVD
SQ QLQERFALTLKAYIECSRPYPAHRFLFLKIMAVLTELRSINAQQTQQLLRIQDSHPFATP
SQ LMQELFSSTDG
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SC translated from EMBL #AF031814
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FT 1 283 
PF00478; IMP dehydrogenase / GMP reductase domai.
FT 35 107 
SM00399; c4gold.
FT 35 111 
PS51030; NUCLEAR_REC_DBD_2.
FT 36 112 
PF00105; Zinc finger, C4 type (two domains).
FT 38 104 
DNA-binding domain [2].
FT 138 158 
helical region H1 [3].
FT 138 431 
putative ligand-binding domain [2].
FT 163 168 
helical region H2 [3].
FT 236 257 
helical region H3 [3].
FT 242 401 
SM00430; holi.
FT 245 425 PF00104; Ligand-binding domain of nuclear hormon.
FT 266 275 helical region H4 [3].
FT 277 287 helical region H5 [3].
FT 305 309 helical region H6 [3].
FT 318 330 helical region H7 [3].
FT 334 345 helical region H8 [3].
FT 357 377 helical region H9 [3].
FT 386 412 helical region H10 [3].
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SF for DNA binding requires dimerization with RXR-alpha, see T05673;
SF direct interaction of ligand-binding domain with steroid ligands (e.g. pregnenolone, pregnenolone 16alpha-carbonitrile) [2];
SF ligand-dependent interaction of ligand-binding domain with coactivator SRC-1 T04632 [2];
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EX adrenal gland (right + left),,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX brain,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX brain,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX epithelial layer of gastrointestinal tract,,,Theiler Stage 26; high; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX heart,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX heart,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX intestine,,,adult; high; Northern blot; mRNA (poly-A); [2].
EX kidney (right and left),,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX kidney (right and left),,,adult; low; Northern blot; mRNA (poly-A); [2].
EX liver,,,Theiler Stage 26; high; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX liver,,,adult; high; Northern blot; mRNA (poly-A); [2].
EX lung,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX lung,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX muscles,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX muscles,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX skin,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX spinal cord,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX spleen,,,adult; none; Northern blot; mRNA (poly-A); [2].
EX stomach,,,adult; low; Northern blot; mRNA (poly-A); [2].
EX testis (right and left),,,adult; none; Northern blot; mRNA (poly-A); [2].
EX thymus,,,Theiler Stage 26; none; RNA-in situ hybridization (not further specified); RNA (undefined); [2].
EX thymus,,,adult; none; Northern blot; mRNA (poly-A); [2].
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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) [7];
FF regulates physiological response to LCA (toxic bile acid) possibly in the cooperation with FXR (NR1H4) [8];
FF unprecedented broad range of ligands among nuclear receptor superfamily [3];
FF activated by a broader range of steroids than isoform T04619 [2];
FF natural ligand: pregnenolone and its metabolites (pregnenolone, 17alpha-hydroxypregnenolone, progesterone, 17alpha-hydroxyprogesterone) [2];
FF natural ligand: 5beta-pregnane-3,20-dione (very potent) [3];
FF natural ligand: lithocholic acid (LCA) [1] [8];
FF natural ligands: bile acid precursors [9];
FF synthetic activating ligands: dexamethasone, (6,16alpha)-dimethyl pregnenolone, GR-antagonist EU486, pregnenolone 16alpha-carbonitrile [2];
FF activated by environmental xenobiotics (polychlorinated biphenyls) and antihormones (cyproterone acetate, spironolactone) [4];
FF ligand spectrum different from orthologs of related species: for example is not activated in the presence of rifampicin in contrast to rabbit ortholog T04630 [3];
FF rifampicin, SR12813, TCPOBOP, phenobarbital have no or little effect on the mouse orthologue, but are activating ligands for the human PXR-isoform1 [7];
FF RU486, clotrimazole, androstanol, 5beta-pregnane-3,20-dione activate both human and mouse PXR-isoform1 [7];
FF feedback regulatory loop: toxic bile acid precursors activate PXR, PXR/RXR-alpha activates cyp3a enzyme genes, CYP3A enzymes serve to metabolize bile acid precursors [9];
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IN T01345 RXR-alpha; human, Homo sapiens.
IN T04632 SRC-1; 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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DR TRANSPATH: MO000028451.
DR EMBL: AF031814;
DR UniProtKB: O54915-1;
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RN [1]; RE0016456.
RX PUBMED: 11248086.
RA Xie W., Radominska-Pandya A., Shi Y., Simon C. M., Nelson M. C., Ong E. S., Waxman D. J., Evans R. M.
RT An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids.
RL Proc. Natl. Acad. Sci. USA 98:3375-3380 (2001).
RN [2]; RE0016460.
RX PUBMED: 9489701.
RA Kliewer S. A., Moore J. T., Wade L., Staudinger J. L., Watson M. A., Jones S. A., McKee D. D., Oliver B. B., Willson T. M., Zetterstrom R. H., Perlmann T., Lehmann J. M.
RT An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway
RL Cell 92:73-82 (1998).
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]; RE0016504.
RX PUBMED: 9855641.
RA Schuetz E. G., Brimer C., Schuetz J. D.
RT Environmental xenobiotics and the antihormones cyproterone acetate and spironolactone use the nuclear hormone pregnenolone X receptor to activate the CYP3A23 hormone response element
RL Mol. Pharmacol. 54:1113-1117 (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]; 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 [7]; 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 [8]; RE0023245.
RX PUBMED: 11248085.
RA Staudinger J. L., Goodwin B., Jones S. A., Hawkins-Brown D., MacKenzie K. I., LaTour A., Liu Y., Klaassen C. D., Brown K. K., Reinhard J., Willson T. M., Koller B. H., Kliewer S. A.
RT The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity.
RL Proc. Natl. Acad. Sci. USA 98:3369-3374 (2001).
RN [9]; RE0023316.
RX PUBMED: 12509506.
RA Goodwin B., Gauthier K. C., Umetani M., Watson M. A., Lochansky M. I., Collins J. L., Leitersdorf E., Mangelsdorf D. J., Kliewer S. A., Repa J. J.
RT Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor.
RL Proc. Natl. Acad. Sci. USA 100:223-228 (2003).
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