Table of Contents - *610147
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Genome
DNA
Protein
Gene Info
Variation
Animal Models
Cellular Pathways
| *610147 | ||||||||
| G PROTEIN-COUPLED BILE ACID RECEPTOR 1; GPBAR1 | ||||||||
| Alternative titles; symbols | ||||||||
| BG37 TGR5 | ||||||||
| HGNC Approved Gene Symbol: GPBAR1 | ||||||||
| Cytogenetic location: 2q35 Genomic coordinates (GRCh37): 2:219,125,737 - 219,128,581 (from NCBI) | ||||||||
| TEXT | ||||||||
| Cloning | ||||||||
| In a database search using sequences of known G protein-coupled receptors (GPCRs) as query, Maruyama et al. (2002) identified a novel human GPCR, BG37, and obtained a full-length cDNA using RACE of fetal cDNA. The BG37 gene encodes a putative 330-amino acid protein with 7 transmembrane domains, characteristic of GPCRs. Maruyama et al. (2002) also identified mouse and rat BG37 sequences, which shared 82 to 91% amino acid identity with the human sequence. Northern blot analysis indicated that BG37 is almost ubiquitously expressed in human tissues including heart, skeletal muscle, spleen, kidney, liver, small intestine, placenta, and leukocytes, but not in brain, colon (without mucosa), thymus, and lung. Further analysis of small intestine and colon with mucosa showed that BG37 is expressed in the stomach, duodenum, ileocecum, ileum, jejunum, ascending colon, transverse colon, descending colon, cecum, and liver, but not in esophagus or rectum. Northern analysis of intestinal cell lines suggested that BG37 is expressed in enteroendocrine cells but not in epithelial cells in vivo. | ||||||||
| Gene Function | ||||||||
| To identify BG37 ligands, Maruyama et al. (2002) expressed BG37 in HEK293 cells and monitored intracellular cAMP and calcium ion levels in response to various compounds. They found that bile acids and steroid hormones rapidly modulated intracellular cAMP levels in BG37-transfected cells in a dose-dependent manner. Furthermore, they showed that this response did not involve nuclear bile acid receptors. The rank order of potency of bile acids in transfected NCI-H716, an enteroendocrine cell line, was the same as that observed for HEK293 cells (lithocholic acid, deoxycholic acid, chenodeoxycholic acid, cholic acid). Maruyama et al. (2002) concluded that BG37 endogenously expressed in NCI-H716 cells functions similarly to that exogenously expressed in HEK293 cells. Watanabe et al. (2006) showed that the administration of bile acids to mice increased energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of bile acids is critically dependent on the induction of the cAMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2; 601413), shown by loss of this effect in D2-null mice. Treatment of brown adipocytes and human skeletal myocytes with bile acids increased D2 activity and oxygen consumption. These effects are independent of FXR-alpha (see 603826), and instead are mediated by increased cAMP production that stems from the binding of bile acids with the G protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism since they coexpress D2 and TGR5. Watanabe et al. (2006) concluded that the bile acid-TGR5-cAMP-D2 signaling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control. | ||||||||
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