Recombinant Human Oxysterols receptor LXR-alpha (NR1H3)

Function

Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920, PubMed:37478846). 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 (PubMed:37478846). 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)

Subcellular Location

Nucleus; Cytoplasm

Tissue Specificity

Visceral organs specific expression. Strong expression was found in liver, kidney and intestine followed by spleen and to a lesser extent the adrenals

Subunit

Heterodimer of NR1H3 and RXR (retinoic acid receptor). Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with SIRT1 and this interaction is inhibited by CCAR2 (PubMed:25661920). Interacts with GPS2 (PubMed:19481530)

• Willy P.J. et al. LXR, a nuclear receptor that defines a distinct retinoid response pathway. — Genes Dev. (1995)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Jakobsson T. et al. GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus. — Mol. Cell (2009)
• Sakurabashi A. et al. CCAR2 negatively regulates nuclear receptor LXRalpha by competing with SIRT1 deacetylase. — J. Steroid Biochem. Mol. Biol. (2015)
• Tsai J.M. et al. UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. — Mol. Cell (2023)