Oxysterols receptor LXR-beta
Also known as: LXRB, NER, NR1H2, UNR
Function
Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. 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.
Classification
- Family (Pfam)
- PF00104 Hormone_recep, PF00105 zf-C4
- InterPro
- Liver_X_rcpt, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 25
- 1P8D X-ray 2.80A
- 1PQ6 X-ray 2.40A
- 1PQ9 X-ray 2.10A
- 1PQC X-ray 2.80A
- 1UPV X-ray 2.10A
- 1UPW X-ray 2.40A
- 3KFC X-ray 2.40A
- 3L0E X-ray 2.30A
- 4DK7 X-ray 2.45A
- 4DK8 X-ray 2.75A
- 4NQA X-ray 3.10A
- 4RAK X-ray 2.04A
- … and 13 more
A predicted model is available from AlphaFold.
Gene Ontology · 48
- GO:0000785 chromatin
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0090575 RNA polymerase II transcription regulator complex
- GO:0034191 apolipoprotein A-I receptor binding
- GO:0051117 ATPase binding
- GO:0031490 chromatin DNA binding
- GO:0003677 DNA binding
- GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
- GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
- GO:0004879 nuclear receptor activity
- GO:0046965 nuclear retinoid X receptor binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0008270 zinc ion binding
- GO:0030154 cell differentiation
- GO:0042632 cholesterol homeostasis
- GO:0009755 hormone-mediated signaling pathway
- GO:0030522 intracellular receptor signaling pathway
- GO:0042789 mRNA transcription by RNA polymerase II
- GO:0010887 negative regulation of cholesterol storage
- GO:0120163 negative regulation of cold-induced thermogenesis
- GO:0045892 negative regulation of DNA-templated transcription
- GO:0010629 negative regulation of gene expression
- GO:0050728 negative regulation of inflammatory response
- GO:0032369 negative regulation of lipid transport
- GO:0010745 negative regulation of macrophage derived foam cell differentiation
- GO:0048550 negative regulation of pinocytosis
- GO:0045861 negative regulation of proteolysis
- GO:1903573 negative regulation of response to endoplasmic reticulum stress
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0060336 negative regulation of type II interferon-mediated signaling pathway
- GO:0036151 phosphatidylcholine acyl-chain remodeling
- GO:0010875 positive regulation of cholesterol efflux
- GO:0032376 positive regulation of cholesterol transport
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045723 positive regulation of fatty acid biosynthetic process
- GO:0010628 positive regulation of gene expression
- GO:0090108 positive regulation of high-density lipoprotein particle assembly
- GO:0010884 positive regulation of lipid storage
- GO:0090187 positive regulation of pancreatic juice secretion
- GO:0090340 positive regulation of secretion of lysosomal enzymes
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0010867 positive regulation of triglyceride biosynthetic process
- GO:0010883 regulation of lipid storage
- GO:0031667 response to nutrient levels
- GO:0048384 retinoic acid receptor signaling pathway
Drugs targeting this protein · 6
- HYODEOXYCHOLIC_ACID agonist
- BMS-779788 agonist
- BMS-852927 modulator
- ROVAZOLAC agonist
- LXR-623 agonist
- ABEQUOLIXRON agonist
Related proteins · sequence + function similarity
- Oxysterols receptor LXR-beta 0.97
- Oxysterols receptor LXR-beta 0.97
- Oxysterols receptor LXR-beta 0.97
- Oxysterols receptor LXR-alpha 0.90
- Oxysterols receptor LXR-alpha 0.89
- Oxysterols receptor LXR-alpha 0.89
- Oxysterols receptor LXR-alpha 0.88
- Retinoic acid receptor RXR-beta 0.85
- Retinoic acid receptor RXR-beta 0.84
- Retinoic acid receptor RXR-beta 0.84
- Retinoic acid receptor RXR-beta 0.84
- Nuclear receptor ROR-gamma 0.81
Co-cited proteins · studied together in the literature
- Glucosylceramide transporter ABCA12 1 shared papers
- Oxysterols receptor LXR-alpha 1 shared papers
- G protein pathway suppressor 2 1 shared papers
- Phospholipid-transporting ATPase ABCA1 1 shared papers
- Nuclear receptor subfamily 5 group A member 2 1 shared papers
- Cell cycle and apoptosis regulator protein 2 1 shared papers
- NAD-dependent protein deacetylase sirtuin-1 1 shared papers
Literature · 8 cited papers
- CCAR2 negatively regulates nuclear receptor LXRalpha by competing with SIRT1 deacetylase. J. Steroid Biochem. Mol. Biol. · 2015
- ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis. Cell Metab. · 2013
- GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response. Genes Dev. · 2010
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The DNA sequence and biology of human chromosome 19. Nature · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. J. Biol. Chem. · 2003
- NER, a new member of the gene family encoding the human steroid hormone nuclear receptor. Gene · 1994