Liver X receptor alpha

Nuclear receptor subfamily 1, group H, member 3
PDB rendering based on 1uhl.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1UHL​, 3IPQ​, 3IPS​, 3IPU​
Identifiers
Symbols	NR1H3 ; LXR-a; LXRA; RLD-1
External IDs	OMIM: 602423 MGI: 1352462 HomoloGene: 21165 IUPHAR: 602 ChEMBL: 2808 GeneCards: NR1H3 Gene
Gene ontology Molecular function • DNA binding • steroid hormone receptor activity • transcription coactivator activity • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • protein binding • zinc ion binding • cholesterol binding • sterol response element binding • sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • receptor complex • RNA polymerase II transcription factor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • gene expression • negative regulation of macrophage derived foam cell differentiation • positive regulation of triglyceride biosynthetic process • positive regulation of receptor biosynthetic process • positive regulation of cholesterol efflux • negative regulation of cholesterol storage • intracellular receptor signaling pathway • positive regulation of cellular protein metabolic process • negative regulation of lipid transport • positive regulation of cholesterol transport • response to progesterone • positive regulation of toll-like receptor 4 signaling pathway • cholesterol homeostasis • regulation of circadian rhythm • negative regulation of macrophage activation • apoptotic cell clearance • steroid hormone mediated signaling pathway • positive regulation of fatty acid biosynthetic process • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation of pinocytosis • negative regulation of inflammatory response • positive regulation of lipoprotein lipase activity • lipid homeostasis • sterol homeostasis • negative regulation of interferon-gamma-mediated signaling pathway • triglyceride homeostasis • cellular response to lipopolysaccharide • negative regulation of pancreatic juice secretion • negative regulation of secretion of lysosomal enzymes • regulation of cholesterol homeostasis • positive regulation of cholesterol homeostasis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10062	22259
Ensembl	ENSG00000025434	ENSMUSG00000002108
UniProt	Q13133	Q9Z0Y9
RefSeq (mRNA)	NM_001130101	NM_001177730
RefSeq (protein)	NP_001123573	NP_001171201
Location (UCSC)	Chr 11: 47.25 – 47.27 Mb	Chr 2: 91.18 – 91.2 Mb
PubMed search

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor subfamily 1, group H, member 3).^[1][2]

Expression

miRNA has-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613.^[3]

Function

The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs) and regulate expression of target genes containing LXR response elements.^[4][5] Restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.^[6]

Interactions

Liver X receptor alpha has been shown to interact with EDF1^[7] and Small heterodimer partner.^[8]

References

1. Miyata KS, McCaw SE, Patel HV, Rachubinski RA, Capone JP (Apr 1996). "The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling". The Journal of Biological Chemistry 271 (16): 9189–92. doi:10.1074/jbc.271.16.9189. PMID 8621574.
2. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ (May 1995). "LXR, a nuclear receptor that defines a distinct retinoid response pathway". Genes & Development 9 (9): 1033–45. doi:10.1101/gad.9.9.1033. PMID 7744246.
3. http://mend.endojournals.org/content/25/4/584.abstract
4. Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B, Gustafsson JA, Grooten J, Huygen K (Jun 2009). "Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice". The Journal of Clinical Investigation 119 (6): 1626–37. doi:10.1172/JCI35288. PMC 2689129. PMID 19436111.
5. "Entrez Gene: nuclear receptor subfamily 1".
6. Gupta DS, Kaul D, Kanwar AJ, Parsad D (Jan 2010). "Psoriasis: crucial role of LXR-alpha RNomics". Genes and Immunity 11 (1): 37–44. doi:10.1038/gene.2009.63. PMID 19798078.
7. Brendel C, Gelman L, Auwerx J (Jun 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology 16 (6): 1367–77. doi:10.1210/mend.16.6.0843. PMID 12040021.
8. 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.

Further reading

• Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM (Feb 1997). "Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway". The Journal of Biological Chemistry 272 (6): 3137–40. doi:10.1074/jbc.272.6.3137. PMID 9013544.
• Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H (Aug 1997). "Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients". Diabetes 46 (8): 1319–27. doi:10.2337/diabetes.46.8.1319. PMID 9231657.
• Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ (May 1998). "Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha". Cell 93 (5): 693–704. doi:10.1016/S0092-8674(00)81432-4. PMID 9630215.
• Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone JP (Nov 1998). "Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha". Molecular and Cellular Endocrinology 146 (1-2): 69–76. doi:10.1016/S0303-7207(98)00196-8. PMID 10022764.
• Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P (Oct 2000). "Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha". Proceedings of the National Academy of Sciences of the United States of America 97 (22): 12097–102. doi:10.1073/pnas.200367697. PMC 17300. PMID 11035776.
• Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B (Jan 2001). "PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway". Nature Medicine 7 (1): 53–8. doi:10.1038/83348. PMID 11135616.
• Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P (Jan 2001). "LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes". Proceedings of the National Academy of Sciences of the United States of America 98 (2): 507–12. doi:10.1073/pnas.021488798. PMC 14617. PMID 11149950.
• Li Y, Bolten C, Bhat BG, Woodring-Dietz J, Li S, Prayaga SK, Xia C, Lala DS (Mar 2002). "Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism". Molecular Endocrinology 16 (3): 506–14. doi:10.1210/me.16.3.506. PMID 11875109.
• Mak PA, Laffitte BA, Desrumaux C, Joseph SB, Curtiss LK, Mangelsdorf DJ, Tontonoz P, Edwards PA (Aug 2002). "Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta". The Journal of Biological Chemistry 277 (35): 31900–8. doi:10.1074/jbc.M202993200. PMID 12032151.
• Brendel C, Gelman L, Auwerx J (Jun 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology 16 (6): 1367–77. doi:10.1210/mend.16.6.0843. PMID 12040021.
• Steffensen KR, Schuster GU, Parini P, Holter E, Sadek CM, Cassel T, Eskild W, Gustafsson JA (May 2002). "Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins". Biochemical and Biophysical Research Communications 293 (5): 1333–40. doi:10.1016/S0006-291X(02)00390-X. PMID 12054659.
• Gbaguidi GF, Agellon LB (Jul 2002). "The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter". Biochimica et Biophysica Acta 1583 (2): 229–36. doi:10.1016/s1388-1981(02)00217-2. PMID 12117567.
• Pawar A, Xu J, Jerks E, Mangelsdorf DJ, Jump DB (Oct 2002). "Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells". The Journal of Biological Chemistry 277 (42): 39243–50. doi:10.1074/jbc.M206170200. PMID 12161442.
• 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.
• Oberkofler H, Schraml E, Krempler F, Patsch W (Apr 2003). "Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha". The Biochemical Journal 371 (Pt 1): 89–96. doi:10.1042/BJ20021665. PMC 1223253. PMID 12470296.
• Wang M, Thomas J, Burris TP, Schkeryantz J, Michael LF (Nov 2003). "Molecular determinants of LXRalpha agonism". Journal of Molecular Graphics & Modelling 22 (2): 173–81. doi:10.1016/S1093-3263(03)00159-1. PMID 12932788.
• 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.

External links

• NR1H3 human gene location in the UCSC Genome Browser.
• NR1H3 human gene details in the UCSC Genome Browser.

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