Search results for NR1H4

Showing 14 results out of 14

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Protein (6 results from a total of 6)

Identifier: R-HSA-5340228
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Identifier: R-HSA-3196157
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Identifier: R-HSA-3196161
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Identifier: R-HSA-3196171
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Identifier: R-HSA-3008624
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Identifier: R-HSA-4755487
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: NR1H4: Q96RI1
Lysine-289 in NR1H4-1 corresponds to lysine-277 in NR1H4-2.

Reaction (5 results from a total of 5)

Identifier: R-HSA-4755419
Species: Homo sapiens
Compartment: nucleoplasm
NR1H4 (FXR, Bile Acid Receptor) is SUMOylated with SUMO1 at lysine-132 and lysine-289 (lysine-122 and lysine-275 of isoform 4, UniProt Q96RI1-2) (Vavassori et al. 2009, Balasubramaniyan et al. 2013). SUMOylation appears to be enhanced when NR1H4 binds ligands (Vavassori et al. 2009). SUMOylated NR1H4 transrepresses genes involved in inflammation (Vavassori et al. 2009) and inhibits ligand-induced activation of FXR targets: bile salt export pump (BSEP) and small heterodimer partner (SHP) (Balasubramaniya et al. 2013).
Identifier: R-HSA-5340195
Species: Homo sapiens
Compartment: nucleoplasm
The nuclear orphan protein bile acid receptor aka farnesoid X-activated receptor (NR1H4 aka FXR) can be activated by bile acids and their salts, its physiological ligands. Mouse Nrih4 is highly expressed in the liver, intestine, kidney and adrenal gland, and to a lesser extent in white adipose tissue and heart (Zhang et al. 2003). Bile acids tested to activate NR1H4 are chenodeoxycholic acid (CDCA), lithocholic acid (LCHA) and deoxycholic acid (DCA) (Parks et al. 1999, Makishima et al. 1999).

Once bound to its ligand, activated NR1H4 binds to retinoic acid receptor RXR-alpha (RXRA) and either nuclear receptor coactivator 1 or 2 (NCOA1 or 2) to function as a ligand-activated transcription factor. This complex repressed transcription of the CYP7A1 gene (encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis) (Holt et al. 2003) and activated the SLC10A2 and 6 genes (encoding Ileal sodium/bile acid cotransporters, both bile acid transporters) (Plass et al. 2002, Ananthanarayanan et al. 2001). Thus, NR1H4 is one of the most important regulators of bile acid metabolism, regulating bile acid synthesis, conjugation, secretion and uptake (Lee et al. 2006, Houten et al. 2006).
Identifier: R-HSA-5340251
Species: Homo sapiens
Compartment: nucleoplasm
The nuclear orphan protein bile acid receptor aka farnesoid X-activated receptor (NR1H4 aka FXR) can be activated by bile acids and their salts, its physiological ligands. Bile acids tested to activate NR1H4 are chenodeoxycholic acid (CDCA), lithocholic acid (LCHA) and deoxycholic acid (DCA) (Parks et al. 1999, Makishima et al. 1999). Once bound to its ligand, activated NR1H4 binds to retinoic acid receptor RXR-alpha (RXRA) and either nuclear receptor coactivator 1 or 2 (NCOA1 or 2) to function as a ligand-activated transcription factor. This complex repressed transcription of the CYP7A1 gene (encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis) (Holt et al. 2003) and activated the SLC10A2 and 6 genes (encoding Ileal sodium/bile acid cotransporters; both bile acid transporters) (Plass et al. 2002, Ananthanarayanan et al. 2001). Thus, NR1H4 is one of the most important regulators of bile acid metabolism, regulating bile acid synthesis, conjugation, secretion and uptake (Lee et al. 2006, Houten et al. 2006).
Identifier: R-HSA-9631296
Species: Homo sapiens
Compartment: nucleoplasm
The ileal bile acid-binding protein (I-BABP, also known as FABP6) is a 14 kDa soluble bile acid (BA) carrier protein which belongs to the fatty acid-binding protein (FABP) family. FABP6 gene expression was directly up-regulated by liver X-receptor α (LXRα or NR1H3) and LXRβ (NR1H2) in human enterocyte-like Caco-2 cells when the cells were transiently cotransfected with a FABP6 promoter fragment cloned upstream of the CAT reporter gene and expression vectors for NR1H3 or NR1H2 and retinoid X receptor α (RXRα) (Landrier JF et al. 2003). Electrophoretic mobility shift assays demonstrated that the NR1H3:RXR heterodimer specifically recognized a farnesoid X‐receptor‐responsive element (FXRE) which functioned as an LXR responsive element (LXRE) in the promoter of FABP6 gene (Landrier JF et al. 2003). Similar data have been reported for the PLTP gene suggesting that the FXRE sequence can function as an LXR‐binding site in different genes (Landrier JF et al. 2002). FABP6 gene expression can be also up-regulated by sterol sensors such as farnesoid X receptor (FXR, NR1H4) or sterol-responsive element-binding protein 1c (SREBP1c) (Mak PA et al. 2002; Landrier JF et al. 2002; Zaghini I et al. 2002).
Identifier: R-HSA-9657791
Species: Homo sapiens
Compartment: cytosol
Expression of the ATP-binding cassette transporter A1 (ABCA1) gene is induced by oxysterol-activated transcription factors liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) and their heterodimeric partners, retinoid X receptors (RXR) via functional LXR response element (LXRE) (Costet P et al. 2000; Ignatova ID et al. 2013). NR1H2, 3-induced expression of ABCA1 is thought to promote ABCA1-mediated cellular cholesterol transport across the plasma membrane to lipid poor apolipoproteins, such as ApoA1 and ApoE in the generation of nascent HDL particles (Vedhachalam C et a. 2007; Ignatova ID et al. 2013). MicroRNA (miR-144) was found to bind the 3'-untranslated region (3'UTR) of ABCA1 mRNA to prohibit translation and reduce ABCA1-mediated cholesterol efflux from hepatocytes (de Aguiar Vallim TQ et al. 2013). In the liver, the farnesoid X receptor (FXR or NR1H4) often acts in opposition to LXRs in the regulation of cholesterol homeostasis. Indeed, FXR activation increases miR-144 expression to decrease hepatic ABCA1 levels and reduce circulating HDL concentrations in mouse models (de Aguiar Vallim TQ et al. 2013). Further, overexpression of miR-144 in a human hepatoma cell line (Hep3B) resulted in a decrease in both ABCA1 protein and efflux of cholesterol to lipid-poor ApoA-I, in the absence of a change in ABCA1 mRNA (de Aguiar Vallim TQ et al. 2013). Hepatic ABCA1 activity is responsible for ~75% of circulating HDL levels (with adipose and intestine contributing to the remainder). While macrophage ABCA1 activity is important in limiting foam cell formation during atherogenesis, macrophage ABCA1-generated HDL particles are not sufficiently abundant to significantly impact the circulating HDL pool. Of note, FXR is not expressed in macrophages, thus FXR/miR-144 is unlikely to contribute greatly to foam cell formation in atherogenesis, but FXR/miR-144 will more dramatically alter circulating serum HDL concentrations through its actions in the liver (de Aguiar Vallim TQ et al. 2013).

Complex (3 results from a total of 3)

Identifier: R-HSA-4755440
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-4755409
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5340186
Species: Homo sapiens
Compartment: nucleoplasm
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