NR1H2

The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, 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 LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).[supplied by OMIM, Jan 2010]

NR1H2

Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity).
Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity).
Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity).
Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity).
Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957).

Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cholesterol homeostasisISS:UniProtKB
Negative regulation of cholesterol storageManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Negative regulation of gene expressionIEA:Ensembl
Negative regulation of interferon-gamma-mediated signaling pathway1 PublicationNAS:BHF-UCL
Negative regulation of lipid transportManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of macrophage derived foam cell differentiation1 PublicationIC:BHF-UCL
Negative regulation of pinocytosisManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of proteolysisIEA:Ensembl
Negative regulation of response to endoplasmic reticulum stressISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:HGNC-UCL
Phosphatidylcholine acyl-chain remodelingISS:UniProtKB
Positive regulation of cellular protein metabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cholesterol effluxManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cholesterol transportManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of fatty acid biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of gene expressionIEA:Ensembl
Positive regulation of high-density lipoprotein particle assemblyIEA:Ensembl
Positive regulation of lipid storageIEA:Ensembl
Positive regulation of lipoprotein lipase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of miRNA transcriptionIEA:Ensembl
Positive regulation of pancreatic juice secretionIEA:Ensembl
Positive regulation of secretion of lysosomal enzymesIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of triglyceride biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Response to nutrient levelsIEA:Ensembl
Retinoic acid receptor signaling pathwayIEA:Ensembl

Nucleus

Sumoylated by SUMO2 at Lys-409 and Lys-447 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation.