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).[1]
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.[1][2]
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.[3]
Interactions
Liver X receptor beta has been shown to interact with NCOA6[4] and Retinoid X receptor alpha.[5]
References
- ^ a b "Entrez Gene: NR1H2 nuclear receptor subfamily 1, group H, member 2".
- ^ Song C, Hiipakka RA, Kokontis JM, Liao S (June 1995). "Ubiquitous receptor: structures, immunocytochemical localization, and modulation of gene activation by receptors for retinoic acids and thyroid hormones". Ann. N. Y. Acad. Sci. 761: 38–49. doi:10.1111/j.1749-6632.1995.tb31367.x. PMID 7625741.
- ^ Lou X., Toresson G., Benod C., Suh J. H., Philips K. J., Webb P.,Gustafsson JA (February 2014). "Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA". Nat. Struct. Mol. Biol. 21 (3): 277–281. doi:10.1038/nsmb.2778. PMID 24561505.
- ^ Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (February 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
- ^ Seol W, Choi HS, Moore DD (January 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Mol. Endocrinol. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.
Further reading
- Seol W, Choi HS, Moore DD (1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors.". Mol. Endocrinol. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.
- Le Beau MM, Song C, Davis EM et al. (1995). "Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization.". Genomics 26 (1): 166–8. doi:10.1016/0888-7543(95)80100-Z. PMID 7782080.
- Shinar DM, Endo N, Rutledge SJ et al. (1994). "NER, a new member of the gene family encoding the human steroid hormone nuclear receptor.". Gene 147 (2): 273–6. doi:10.1016/0378-1119(94)90080-9. PMID 7926814.
- Song C, Kokontis JM, Hiipakka RA, Liao S (1994). "Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors.". Proc. Natl. Acad. Sci. U.S.A. 91 (23): 10809–13. doi:10.1073/pnas.91.23.10809. PMC 45115. PMID 7971966.
- Janowski BA, Grogan MJ, Jones SA et al. (1999). "Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta.". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 266–71. doi:10.1073/pnas.96.1.266. PMC 15128. PMID 9874807.
- Feltkamp D, Wiebel FF, Alberti S, Gustafsson JA (1999). "Identification of a novel DNA binding site for nuclear orphan receptor OR1.". J. Biol. Chem. 274 (15): 10421–9. doi:10.1074/jbc.274.15.10421. PMID 10187832.
- Lee SK, Jung SY, Kim YS et al. (2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2.". Mol. Endocrinol. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
- Whitney KD, Watson MA, Goodwin B et al. (2001). "Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages.". J. Biol. Chem. 276 (47): 43509–15. doi:10.1074/jbc.M106155200. PMID 11546778.
- Whitney KD, Watson MA, Collins JL et al. (2003). "Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system.". Mol. Endocrinol. 16 (6): 1378–85. doi:10.1210/me.16.6.1378. PMID 12040022.
- Brendel C, Schoonjans K, Botrugno OA et al. (2003). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity.". Mol. Endocrinol. 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
- Mo J, Fang SJ, Chen W, Blobe GC (2003). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta.". J. Biol. Chem. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Williams S, Bledsoe RK, Collins JL et al. (2003). "X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch.". J. Biol. Chem. 278 (29): 27138–43. doi:10.1074/jbc.M302260200. PMID 12736258.
- Färnegårdh M, Bonn T, Sun S et al. (2003). "The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.". J. Biol. Chem. 278 (40): 38821–8. doi:10.1074/jbc.M304842200. PMID 12819202.
- Fukuchi J, Song C, Ko AL, Liao S (2004). "Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors.". Steroids 68 (7–8): 685–91. doi:10.1016/S0039-128X(03)00100-4. PMID 12957674.
- Hoerer S, Schmid A, Heckel A et al. (2004). "Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist". J. Mol. Biol. 334 (5): 853–61. doi:10.1016/j.jmb.2003.10.033. PMID 14643652.
- Walczak R, Joseph SB, Laffitte BA et al. (2004). "Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors". J. Biol. Chem. 279 (11): 9905–11. doi:10.1074/jbc.M310587200. PMID 14699103.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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