Biology:Liver X receptor beta

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the NR1H2 gene (nuclear receptor subfamily 1, group H, member 2).

Function

The liver X receptors (LXRs) were originally identified as orphan members of the nuclear receptor superfamily because their ligands were unknown. Like other receptors in the family, LXRs heterodimerize with retinoid X receptor and bind to specific response elements (LXREs) characterized by direct repeats separated by 4 nucleotides. Two genes, alpha (LXRA) and beta, are known to encode LXR proteins.

Structure

Crystal structure of human liver X receptor β(LXRβ) forming heterodimer with its partner retinoid X receptor α(RXRα) on its cognate element, an AGGTCA direct repeat spaced by 4 nt shows an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element.

Interactions

Liver X receptor beta has been shown to interact with NCOA6 and Retinoid X receptor alpha.

Further reading

• "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology 9 (1): 72–85. Jan 1995. doi:10.1210/mend.9.1.7760852. PMID 7760852. 
• "Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization". Genomics 26 (1): 166–8. Mar 1995. doi:10.1016/0888-7543(95)80100-Z. PMID 7782080. 
• "NER, a new member of the gene family encoding the human steroid hormone nuclear receptor". Gene 147 (2): 273–6. Sep 1994. doi:10.1016/0378-1119(94)90080-9. PMID 7926814. 
• "Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors". Proceedings of the National Academy of Sciences of the United States of America 91 (23): 10809–13. Nov 1994. doi:10.1073/pnas.91.23.10809. PMID 7971966. Bibcode: 1994PNAS...9110809S. 
• "Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta". Proceedings of the National Academy of Sciences of the United States of America 96 (1): 266–71. Jan 1999. doi:10.1073/pnas.96.1.266. PMID 9874807. Bibcode: 1999PNAS...96..266J. 
• "Identification of a novel DNA binding site for nuclear orphan receptor OR1". The Journal of Biological Chemistry 274 (15): 10421–9. Apr 1999. doi:10.1074/jbc.274.15.10421. PMID 10187832. 
• "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Molecular Endocrinology 15 (2): 241–54. Feb 2001. doi:10.1210/mend.15.2.0595. PMID 11158331. 
• "Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages". The Journal of Biological Chemistry 276 (47): 43509–15. Nov 2001. doi:10.1074/jbc.M106155200. PMID 11546778. 
• "Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system". Molecular Endocrinology 16 (6): 1378–85. Jun 2002. doi:10.1210/mend.16.6.0835. PMID 12040022. 
• "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology 16 (9): 2065–76. Sep 2002. doi:10.1210/me.2001-0194. PMID 12198243. 
• "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". The Journal of Biological Chemistry 277 (52): 50788–94. Dec 2002. doi:10.1074/jbc.M210376200. PMID 12393874. 
• "X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch". The Journal of Biological Chemistry 278 (29): 27138–43. Jul 2003. doi:10.1074/jbc.M302260200. PMID 12736258. 
• "The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands". The Journal of Biological Chemistry 278 (40): 38821–8. Oct 2003. doi:10.1074/jbc.M304842200. PMID 12819202. 
• "Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors". Steroids 68 (7–8): 685–91. Sep 2003. doi:10.1016/S0039-128X(03)00100-4. PMID 12957674. 
• "Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist". Journal of Molecular Biology 334 (5): 853–61. Dec 2003. doi:10.1016/j.jmb.2003.10.033. PMID 14643652. 
• "Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors". The Journal of Biological Chemistry 279 (11): 9905–11. Mar 2004. doi:10.1074/jbc.M310587200. PMID 14699103. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.