NR1H3

The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Nuclear Receptor Subfamily 1 Group H Member 3

Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920).
Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES (By similarity).
LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity).
Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (PubMed:19481530).
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. 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).

Apoptotic cell clearanceManual Assertion Based On ExperimentIMP:UniProtKB
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to lipopolysaccharideManual Assertion Based On ExperimentIDA:BHF-UCL
Cholesterol homeostasisManual Assertion Based On ExperimentIDA:BHF-UCL
Hormone-mediated signaling pathwayManual Assertion Based On ExperimentIDA:ComplexPortal
Lipid homeostasisISS:BHF-UCL
mRNA transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ComplexPortal
Negative regulation of cholesterol storageManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Negative regulation of inflammatory responseISS:BHF-UCL
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 activationISS:BHF-UCL
Negative regulation of macrophage derived foam cell differentiation1 PublicationIC:BHF-UCL
Negative regulation of pancreatic juice secretionISS: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 secretion of lysosomal enzymesISS:BHF-UCL
Negative regulation of transcription by RNA polymerase IIISS:BHF-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 ExperimentIDA:UniProtKB
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 lipoprotein lipase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of toll-like receptor 4 signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
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 transporter activityManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of triglyceride biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of circadian rhythmManual Assertion Based On ExperimentTAS:BHF-UCL
Response to progesteroneManual Assertion Based On ExperimentIDA:BHF-UCL
Sterol homeostasisISS:BHF-UCL
Triglyceride homeostasisISS:BHF-UCL

Nucleus
Cytoplasm

Ubiquitinated leading to its degradation by the proteasome.