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Details on Person The ATP-binding cassette (ABC) transporter 5 (ABCG5) gene is...
| Class:Id | Summation:9029584 |
|---|---|
| _displayName | The ATP-binding cassette (ABC) transporter 5 (ABCG5) gene is... |
| _timestamp | 2019-08-14 03:34:26 |
| created | [InstanceEdit:9029533] Shamovsky, Veronica, 2017-11-20 |
| literatureReference | [LiteratureReference:9029535] Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta [LiteratureReference:9029545] Cholesterol feeding strongly reduces hepatic VLDL-triglyceride production in mice lacking the liver X receptor alpha [LiteratureReference:9029563] Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor [LiteratureReference:265544] Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters [LiteratureReference:9613811] Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8 [LiteratureReference:265510] ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion [LiteratureReference:9029581] Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface [LiteratureReference:5679149] ABCG5/ABCG8 in cholesterol excretion and atherosclerosis [LiteratureReference:9613821] Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8 [LiteratureReference:9613806] Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients [LiteratureReference:9029553] Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster [LiteratureReference:9613820] The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter |
| modified | [InstanceEdit:9611809] Shamovsky, Veronica, 2018-06-19 [InstanceEdit:9613810] Shamovsky, Veronica, 2018-07-19 [InstanceEdit:9634037] Shamovsky, Veronica, 2019-01-03 [InstanceEdit:9658282] Shamovsky, Veronica, 2019-08-12 [InstanceEdit:9658426] Shamovsky, Veronica, 2019-08-14 |
| text | The ATP-binding cassette (ABC) transporter 5 (ABCG5) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. In mammalian cells, ABCG8 and ABCG5 form obligate heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion (Berge KE et al. 2000; Graf GA et al. 2002, 2003; reviewed by Yu XH et al. 2014). Consistent with these functions, ABCG5 and ABCG8 are expressed almost exclusively on the brush border membranes of enterocytes and in the canalicular membranes of hepatocytes (Yu XH et al. 2014). ABCG5 and ABCG8 mutations are responsible for sitosterolemia, a genetic disorder in which patients accumulate cholesterol and plant sterols in the circulation and are at increased risk for developing premature cardiovascular disease (Berge KE et al. 2000; Lee MH et al. 2001). In the pathogenesis of cholesterol gallstone disease, the upregulation of ABCG5 and ABCG8 in gallstone patients, possibly mediated by increased NR1H3 (LXRα), may contribute to the cholesterol supersaturation of bile (Jiang ZY et al. 2008). As shown in mice, both Abcg8 and Abcg5 are target genes of the liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) (Repa JJ et al. 2002; van der Veen et al. 2007). The synthetic LXR agonist, T0901317, markedly upregulated Abcg5 and Abcg8 mRNA levels in the small intestine and liver of wild type but not NR1H3 knockout mice (Repa JJ et al. 2002; van der Veen et al. 2007; Yu L et al. 2003). The human ABCG8 and ABCG5 genes, each with 13 exons, are located next to each other in a head-to-head configuration on chromosome 2p21 (Remaley AT et al. 2002). Their start codons are separated by a 374-bp intergenic region, which is highly conserved among several species (Remaley AT et al. 2002). This intergenic region acts as a bidirectional promoter, and harbors potential binding sites for hepatocyte nuclear factor 4α (HNF4α), liver receptor homolog 1 (LRH1) and GATA transcription factors (Remaley AT et al. 2002; Sumi K et al. 2007; Freeman LA et al. 2004). Regarding sterol/LXRs regulation of ABCG5, electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated the binding of NR1H3 to two intronic regions of the human ABCG8 gene to confer NR1H3-mediated regulation in human liver carcinoma HepG2 cells (Back SS et al. 2013). |
| (summation) | [BlackBoxEvent:9029531] Expression of ABCG5 regulated by NR1H2,3 [Homo sapiens] |
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