AC T02752
XX
ID T02752
XX
DT 04.06.1999 (created); mpr.
DT 11.12.2015 (updated); sup.
CO Copyright (C), QIAGEN.
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FA LXR-alpha
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SY liver X receptor alpha; LXR; LXR A; LXR-A; LXRA; NR1H3; nuclear orphan receptor LXR-alpha.
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OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
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GE G004013 NR1H3; HGNC: NR1H3.
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CL C0002; CC (rec); 2.1.2.7.1.
XX
SF two splice variants that differ by the start of transcription and as a result have different first exons: exon 1B is located 345 bp downstream of exon 1A [8];
SF heterodimerization with RXR-alpha T01345 [1];
SF as a heterodimer with RXR-alpha binds to DR4-like sequences;
SF no formation of a biologically active heterodimer with RAR-alpha [1];
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CP liver, intestine, adipose tissue, macrophages.
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FF activation by oxysterols (natural ligands): 24(S),25-epoxycholesterol, 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol [4] [7];
FF ligand selectivity distinct from isoform T04453 (stronger binding to 5,6-24(S),25-di-epoxycholesterol) [4];
FF heterodimer with RXR-alpha is also activated by RXR-ligands: 9-cis retinoic acid and methoprene acid strongly induce transcriptional transactivation [1];
FF in response to 9-cis retinoid acid nearly identical concentration-dependent activation profile to that of RXR-alpha T01345 [1];
FF seems to act as a tissue-specific cofactor that permits RXR-alpha T01345 to function as a potent receptor of 9-cis retinoid acid with a distinct target gene specificity in comparison to other RXR-heterodimers [1];
FF is highly induced in macrophages in response to lipid loading [8];
FF LXR-alpha factor binds to and positively regulates its encoding gene [8];
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IN T09944 DAX1; human, Homo sapiens.
IN T19612 DRIP205; mouse, Mus musculus.
IN T02938 FOXO3a; human, Homo sapiens.
IN T08861 NCOR1-isoform1; human, Homo sapiens.
IN T04687 NCOR1; human, Homo sapiens.
IN T08632 PPARalpha-isoform1; human, Homo sapiens.
IN T09957 PPARbeta; Mammalia.
IN T05351 PPARgamma; human, Homo sapiens.
IN T01345 RXR-alpha; human, Homo sapiens.
IN T09964 RXR-alpha; Mammalia.
IN T01334 RXR-beta; human, Homo sapiens.
IN T04807 RXR-gamma; human, Homo sapiens.
IN T08947 SHP; mouse, Mus musculus.
IN T04689 SMRT; human, Homo sapiens.
IN T04632 SRC-1; human, Homo sapiens.
IN T21552 SRC-1; Mammalia.
IN T04640 SRC3; human, Homo sapiens.
IN T22485 ZXDL; human, Homo sapiens.
XX
MX M00965 V$DR4_Q2.
MX M00647 V$LXR_Q3.
MX M03795 V$LXR_Q6.
MX M07280 V$NR1NR2_Q3.
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BS R09975.
BS R57630.
BS R63130.
BS R62341.
BS R31327.
BS R59022.
BS R68459.
BS R62982.
BS R19146.
BS R28551.
BS R09974.
XX
DR TRANSPATH: MO000026726.
DR UniProtKB: Q13133;
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RN [1]; RE0010391.
RX PUBMED: 7744246.
RA Willy P. J., Umesono K., Ong E. S., Evans R. M., Heyman R. A., Mangelsdorf D. J.
RT LXR, a nuclear receptor that defines a distinct retinoid response pathway
RL Genes Dev. 9:1033-1045 (1995).
RN [2]; RE0013625.
RX PUBMED: 10219237.
RA Nuclear Receptors Nomenclature Committee.
RT A unified nomenclature system for the nuclear receptor superfamily
RL Cell 97:161-163 (1999).
RN [3]; RE0013643.
RX PUBMED: 7926814.
RA Shinar D. M., Endo N., Rutledge S. J., Vogel R., Rodan G. A., Schmidt A.
RT NER, a new member of the gene family encoding the human steroid hormone nuclear receptor
RL Gene 147:273-276 (1994).
RN [4]; RE0013644.
RX PUBMED: 9874807.
RA Janowski B. A., Grogan M. J., Jones S. A., Wisely G. B., Kliewer S. A., Corey E. J., Mangelsdorf D. J.
RT Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta
RL Proc. Natl. Acad. Sci. USA 96:266-271 (1999).
RN [5]; RE0016034.
RX PUBMED: 7971966.
RA Song C., Kokontis J. M., Hiipakka R. A., Liao S.
RT Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors
RL Proc. Natl. Acad. Sci. USA 91:10809-10813 (1994).
RN [6]; RE0016040.
RX PUBMED: 11149950.
RA Laffitte B. A., Repa J. J., Joseph S. B., Wilpitz D. C., Kast H. R., Mangelsdorf D. J., Tontonoz P.
RT LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes
RL Proc. Natl. Acad. Sci. USA 98:507-512 (2001).
RN [7]; RE0016108.
RX PUBMED: 9013544.
RA Lehmann J. M., Kliewer S. A., Moore L. B., Smith-Oliver T. A., Oliver B. B., Su J. L., Sundseth S. S., Winegar D. A., Blanchard D. E., Spencer T. A., Willson T. M.
RT Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway
RL J. Biol. Chem. 272:3137-3140 (1997).
RN [8]; RE0023618.
RX PUBMED: 11604492.
RA Laffitte B. A., Joseph S. B., Walczak R., Pei L., Wilpitz D. C., Collins J. L., Tontonoz P.
RT Autoregulation of the human liver X receptor alpha promoter.
RL Mol. Cell. Biol. 21:7558-7568 (2001).
RN [9]; RE0042891.
RX PUBMED: 12198243.
RA Brendel C., Schoonjans K., Botrugno O. A., Treuter E., Auwerx J.
RT The Small Heterodimer Partner Interacts with the Liver X Receptor alpha and Represses Its Transcriptional Activity
RL Mol. Endocrinol. 16:2065-76 (2002).
RN [10]; RE0047844.
RX PUBMED: 15722453.
RA Yue L., Ye F., Gui C., Luo H., Cai J., Shen J., Chen K., Shen X., Jiang H.
RT Ligand-binding regulation of LXR/RXR and LXR/PPAR heterodimerizations: SPR technology-based kinetic analysis correlated with molecular dynamics simulation.
RL Protein Sci. 14:812-822 (2005).
RN [11]; RE0050893.
RX PUBMED: 15145977.
RA Nishimaki-Mogami T., Une M., Fujino T., Sato Y., Tamehiro N., Kawahara Y., Shudo K., Inoue K.
RT Identification of intermediates in the bile acid synthetic pathway as ligands for the farnesoid X receptor.
RL J. Lipid Res. 45:1538-1545 (2004).
RN [12]; RE0050921.
RX PUBMED: 10936612.
RA Song C., Hiipakka R. A., Liao S.
RT Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and analogs.
RL Steroids 65:423-427 (2000).
RN [13]; RE0051017.
RX PUBMED: 16857673.
RA Yang C., McDonald J. G., Patel A., Zhang Y., Umetani M., Xu F., Westover E. J., Covey D. F., Mangelsdorf D. J., Cohen J. C., Hobbs H. H.
RT Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands.
RL J. Biol. Chem. 281:27816-27826 (2006).
RN [14]; RE0051131.
RX PUBMED: 16904112.
RA Chen M., Bradley M. N., Beaven S. W., Tontonoz P.
RT Phosphorylation of the liver X receptors.
RL FEBS Lett. 580:4835-4841 (2006).
RN [15]; RE0051194.
RX PUBMED: 16154115.
RA Huang T. H., Razmovski-Naumovski V., Salam N. K., Duke R. K., Tran V. H., Duke C. C., Roufogalis B. D.
RT A novel LXR-alpha activator identified from the natural product Gynostemma pentaphyllum.
RL Biochem. Pharmacol. 70:1298-1308 (2005).
RN [16]; RE0051265.
RX PUBMED: 17296605.
RA Yamamoto T., Shimano H., Inoue N., Nakagawa Y., Matsuzaka T., Takahashi A., Yahagi N., Sone H., Suzuki H., Toyoshima H., Yamada N.
RT Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver.
RL J. Biol. Chem. 282:11687-11695 (2007).
RN [17]; RE0051310.
RX PUBMED: 16354658.
RA Albers M., Blume B., Schlueter T., Wright M. B., Kober I., Kremoser C., Deuschle U., Koegl M.
RT A novel principle for partial agonism of liver X receptor ligands. Competitive recruitment of activators and repressors.
RL J. Biol. Chem. 281:4920-4930 (2006).
RN [18]; RE0054989.
RX PUBMED: 15604093.
RA Albers M., Kranz H., Kober I., Kaiser C., Klink M., Suckow J., Kern R., Koegl M.
RT Automated yeast two-hybrid screening for nuclear receptor-interacting proteins.
RL Mol. Cell. Proteomics 4:205-213 (2005).
RN [19]; RE0064089.
RX PUBMED: 18789440.
RA Hao X. R., Cao D. L., Hu Y. W., Li X. X., Liu X. H., Xiao J., Liao D. F., Xiang J., Tang C. K.
RT IFN-gamma down-regulates ABCA1 expression by inhibiting LXRalpha in a JAK/STAT signaling pathway-dependent manner.
RL Atherosclerosis 203:417-428 (2009).
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