NR1H2

Description

The NR1H2 (nuclear receptor subfamily 1 group H member 2) is a protein-coding gene located on chromosome 19.

Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the NR1H2 gene (nuclear receptor subfamily 1, group H, member 2). The liver X receptors (LXRs) were originally identified as orphan members of the nuclear receptor superfamily because their ligands were unknown. Like other receptors in the family, LXRs heterodimerize with retinoid X receptor and bind to specific response elements (LXREs) characterized by direct repeats separated by 4 nucleotides. Two genes, alpha (LXRA) and beta, are known to encode LXR proteins. Crystal structure of human liver X receptor β(LXRβ) forming heterodimer with its partner retinoid X receptor α(RXRα) on its cognate element, an AGGTCA direct repeat spaced by 4 nt shows an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element. Liver X receptor beta has been shown to interact with NCOA6 and Retinoid X receptor alpha.

NR1H2 is a nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. It preferentially binds to double-stranded oligonucleotide direct repeats with a consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). NR1H2 regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR, and LRP8; DLDLR and LRP8. It functionally interacts with RORA for the regulation of genes involved in liver metabolism. NR1H2 induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis. Through LPCAT3, it 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, NR1H2 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators. NR1H2 plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: it inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex.

NR1H2 is also known as LXR-b, LXRB, NER, NER-I, RIP15, UNR.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing