Liver X receptor alpha

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).[5][6]

NR1H3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNR1H3, LXR-a, LXRA, RLD-1, Liver X receptor alpha, nuclear receptor subfamily 1 group H member 3
External IDsOMIM: 602423 MGI: 1352462 HomoloGene: 21165 GeneCards: NR1H3
Orthologs
SpeciesHumanMouse
Entrez

10062

22259

Ensembl

ENSG00000025434

ENSMUSG00000002108

UniProt

Q13133

Q9Z0Y9

RefSeq (mRNA)

NM_001130101
NM_001130102
NM_001251934
NM_001251935
NM_005693

NM_001177730
NM_013839
NM_001355279

RefSeq (protein)

NP_001171201
NP_038867
NP_001342208

Location (UCSC)Chr 11: 47.25 – 47.27 MbChr 2: 91.01 – 91.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Expression

miRNA hsa-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.[7]

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. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases.[8] 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.[9][10] Restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.[11]

Interactions

Liver X receptor alpha has been shown to interact with EDF1[12] and Small heterodimer partner.[13] LXRα activates the transcription factor SREBP-1c, resulting in lipogenesis.[14]

In 2016, a study found 70% of individuals in two families with a rare form of rapidly progressing multiple sclerosis had a mutation in NR1H3.[15] However, an analysis from The International Multiple Sclerosis Genetics Consortium using a 13-fold larger sample size could not find any evidence that the mutation in question (p.Arg415Gln) associated with multiple sclerosis, refuting these findings.[16]

References
  1. GRCh38: Ensembl release 89: ENSG00000025434 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000002108 - 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. 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.
  6. 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.
  7. http://mend.endojournals.org/content/25/4/584.abstract
  8. Christoffolete MA, Doleschall M, Egri P, Liposits Z, Zavacki AM, Bianco AC, Gereben B (2010). "Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway". The Journal of Endocrinology. 205 (2): 179–86. doi:10.1677/JOE-09-0448. PMC 3133926. PMID 20176747.
  9. 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.
  10. "Entrez Gene: nuclear receptor subfamily 1".
  11. 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.
  12. 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.
  13. 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.
  14. Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, Unger RH (2010). "Leptin therapy in insulin-deficient type I diabetes". Proceedings of the National Academy of Sciences of the United States of America. 107 (11): 4813–9. doi:10.1073/pnas.0909422107. PMC 2841945. PMID 20194735.
  15. Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, Yee IM, de Lemos M, Greenwood T, Lee JD, Wright G, Ross CJ, Zhang S, Song W, Vilariño-Güell C (2016). "Nuclear Receptor NR1H3 in Familial Multiple Sclerosis". Neuron. 90 (5): 948–54. doi:10.1016/j.neuron.2016.04.039. PMC 5092154. PMID 27253448.
  16. Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, et al. (International Multiple Sclerosis Genetics Consortium) (October 2016). "NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk". Neuron. 92 (2): 333–335. doi:10.1016/j.neuron.2016.09.052. PMC 5641967. PMID 27764667.

Further reading

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