Liver X receptor beta

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).[5]

NR1H2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1P8D, 1PQ6, 1PQ9, 1PQC, 1UPV, 1UPW, 3KFC, 3L0E, 4DK7, 4DK8, 4RAK, 5HJP, 4NQA, 5I4V,%%s4NQA
Identifiers
Aliases	NR1H2, LXR-b, LXRB, NER, NER-I, RIP15, UNR, Liver X receptor beta, nuclear receptor subfamily 1 group H member 2
External IDs	OMIM: 600380 MGI: 1352463 HomoloGene: 21397 GeneCards: NR1H2
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.33 Start 50,329,653 bp[1] End 50,383,388 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B3 Start 44,549,616 bp[2] End 44,553,951 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • sequence-specific DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • ATPase binding • zinc ion binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • metal ion binding • retinoid X receptor binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • steroid hormone receptor activity • apolipoprotein A-I receptor binding • GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity • GO:0001948 protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • transcription regulatory region sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • transcription factor binding • ligand-dependent nuclear receptor transcription coactivator activity • signaling receptor activity Cellular component • cytoplasm • nucleoplasm • cell nucleus • RNA polymerase II transcription factor complex Biological process • positive regulation of high-density lipoprotein particle assembly • negative regulation of proteolysis • positive regulation of triglyceride biosynthetic process • positive regulation of cellular protein metabolic process • negative regulation of interferon-gamma-mediated signaling pathway • positive regulation of cholesterol transport • regulation of transcription, DNA-templated • cellular lipid metabolic process • regulation of transcription from RNA polymerase II promoter • positive regulation of secretion of lysosomal enzymes • positive regulation of lipid storage • positive regulation of lipoprotein lipase activity • negative regulation of transcription from RNA polymerase II promoter • positive regulation of fatty acid biosynthetic process • negative regulation of gene expression • transcription, DNA-templated • positive regulation of transcription, DNA-templated • negative regulation of cholesterol storage • negative regulation of pinocytosis • positive regulation of gene expression • retinoic acid receptor signaling pathway • positive regulation of cholesterol efflux • positive regulation of pancreatic juice secretion • lipid homeostasis • negative regulation of lipid transport • transcription initiation from RNA polymerase II promoter • negative regulation of transcription, DNA-templated • negative regulation of macrophage derived foam cell differentiation • positive regulation of transcription from RNA polymerase II promoter • steroid hormone mediated signaling pathway • cholesterol homeostasis • lipid metabolism • multicellular organism development • cell differentiation • cellular response to lipopolysaccharide • negative regulation of cold-induced thermogenesis • intracellular receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7376	22260
Ensembl	ENSG00000131408	ENSMUSG00000060601
UniProt	P55055	Q60644
RefSeq (mRNA)	NM_007121 NM_001256647	NM_001285517 NM_001285518 NM_001285519 NM_009473
RefSeq (protein)	NP_001243576 NP_009052 NP_009052.3	NP_001272446 NP_001272447 NP_001272448 NP_033499
Location (UCSC)	Chr 19: 50.33 – 50.38 Mb	Chr 7: 44.55 – 44.55 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5][6]

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.[7]

Interactions

Liver X receptor beta has been shown to interact with NCOA6[8] and Retinoid X receptor alpha.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000131408 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000060601 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: NR1H2 nuclear receptor subfamily 1, group H, member 2".
6. Song C, Hiipakka RA, Kokontis JM, Liao S (Jun 1995). "Ubiquitous receptor: structures, immunocytochemical localization, and modulation of gene activation by receptors for retinoic acids and thyroid hormones". Annals of the New York Academy of Sciences. 761: 38–49. doi:10.1111/j.1749-6632.1995.tb31367.x. PMID 7625741.
7. Lou X, Toresson G, Benod C, Suh JH, Philips KJ, Webb P, Gustafsson JA (Mar 2014). "Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA". Nature Structural & Molecular Biology. 21 (3): 277–81. doi:10.1038/nsmb.2778. PMID 24561505.
8. Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (Feb 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Molecular Endocrinology. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
9. Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.

Further reading

• Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.
• Le Beau MM, Song C, Davis EM, Hiipakka RA, Kokontis JM, Liao S (Mar 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, Vogel R, Rodan GA, Schmidt A (Sep 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 (Nov 1994). "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. doi:10.1073/pnas.91.23.10809. PMC 45115. PMID 7971966.
• Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ (Jan 1999). "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. doi:10.1073/pnas.96.1.266. PMC 15128. PMID 9874807.
• Feltkamp D, Wiebel FF, Alberti S, Gustafsson JA (Apr 1999). "Identification of a novel DNA binding site for nuclear orphan receptor OR1". The Journal of Biological Chemistry. 274 (15): 10421–9. doi:10.1074/jbc.274.15.10421. PMID 10187832.
• Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (Feb 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Molecular Endocrinology. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
• Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, Wilson JG, Willson TM, Collins JL, Kliewer SA (Nov 2001). "Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages". The Journal of Biological Chemistry. 276 (47): 43509–15. doi:10.1074/jbc.M106155200. PMID 11546778.
• Whitney KD, Watson MA, Collins JL, Benson WG, Stone TM, Numerick MJ, Tippin TK, Wilson JG, Winegar DA, Kliewer SA (Jun 2002). "Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system". Molecular Endocrinology. 16 (6): 1378–85. doi:10.1210/me.16.6.1378. PMID 12040022.
• Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (Sep 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
• Mo J, Fang SJ, Chen W, Blobe GC (Dec 2002). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". The Journal of Biological Chemistry. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874.
• Williams S, Bledsoe RK, Collins JL, Boggs S, Lambert MH, Miller AB, Moore J, McKee DD, Moore L, Nichols J, Parks D, Watson M, Wisely B, Willson TM (Jul 2003). "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. doi:10.1074/jbc.M302260200. PMID 12736258.
• Färnegårdh M, Bonn T, Sun S, Ljunggren J, Ahola H, Wilhelmsson A, Gustafsson JA, Carlquist M (Oct 2003). "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. doi:10.1074/jbc.M304842200. PMID 12819202.
• Fukuchi J, Song C, Ko AL, Liao S (Sep 2003). "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, Budzinski RM, Nar H (Dec 2003). "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. doi:10.1016/j.jmb.2003.10.033. PMID 14643652.
• Walczak R, Joseph SB, Laffitte BA, Castrillo A, Pei L, Tontonoz P (Mar 2004). "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. 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.