Liver X receptor alpha

NR1H3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UHL, 3IPQ, 3IPS, 3IPU, 5AVI, 5AVL, 5HJS
Identifiers
Aliases	NR1H3, LXR-a, LXRA, RLD-1, Liver X receptor alpha, nuclear receptor subfamily 1 group H member 3
External IDs	OMIM: 602423; MGI: 1352462; HomoloGene: 21165; GeneCards: NR1H3; OMA:NR1H3 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p11.2 Start 47,248,300 bp[1] End 47,269,032 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 E1|2 50.52 cM Start 91,014,406 bp[2] End 91,033,179 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver mucosa of transverse colon spleen tibial nerve subcutaneous adipose tissue canal of the cervix gallbladder lymph node right lobe of thyroid gland right adrenal cortex Top expressed in right kidney left lobe of liver Ileal epithelium muscle of thigh lactiferous gland proximal tubule brown adipose tissue white adipose tissue subcutaneous adipose tissue duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cholesterol binding protein binding zinc ion binding nuclear receptor activity sterol response element binding steroid hormone receptor activity DNA binding sequence-specific DNA binding metal ion binding DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific transcription coactivator activity transcription cis-regulatory region binding RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor binding nuclear receptor coactivator activity signaling receptor activity Cellular component receptor complex nucleoplasm RNA polymerase II transcription regulator complex nucleus cytoplasm Biological process positive regulation of toll-like receptor 4 signaling pathway sterol homeostasis negative regulation of pancreatic juice secretion negative regulation of inflammatory response cellular response to lipopolysaccharide negative regulation of lipid transport positive regulation of lipoprotein lipase activity lipid homeostasis triglyceride homeostasis negative regulation of macrophage activation negative regulation of macrophage derived foam cell differentiation positive regulation of cholesterol transport negative regulation of cholesterol storage regulation of transcription, DNA-templated positive regulation of triglyceride biosynthetic process positive regulation of cholesterol efflux positive regulation of protein metabolic process negative regulation of interferon-gamma-mediated signaling pathway regulation of circadian rhythm transcription, DNA-templated negative regulation of transcription by RNA polymerase II response to progesterone steroid hormone mediated signaling pathway apoptotic cell clearance positive regulation of fatty acid biosynthetic process transcription initiation from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II negative regulation of secretion of lysosomal enzymes negative regulation of pinocytosis positive regulation of transcription, DNA-templated intracellular receptor signaling pathway cholesterol homeostasis lipid metabolism multicellular organism development cell differentiation negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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_001123573 NP_001123574 NP_001238863 NP_001238864 NP_005684 NP_001350524 NP_005684.2 NP_001171201 NP_038867 NP_001342208 Location (UCSC) Chr 11: 47.25 – 47.27 Mb Chr 2: 91.01 – 91.03 Mb PubMed search [3] [4]
Wikidata
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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]

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]

Link to multiple sclerosis

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

Further reading

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.