| Tchem | Free fatty acid receptor 2 |
G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).
This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]
This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]
Comments
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6694 | 5.5e-46 |
| ulcerative colitis | 1819 | 2.2e-03 |
| interstitial cystitis | 2312 | 8.0e-03 |
| Multiple Sclerosis | 540 | 2.5e-02 |
| Rheumatoid arthritis | 1191 | 4.5e-02 |
| Disease | log2 FC | p |
|---|---|---|
| interstitial cystitis | 1.200 | 8.0e-03 |
| Multiple Sclerosis | 1.200 | 2.5e-02 |
| psoriasis | 1.400 | 5.5e-46 |
| Rheumatoid arthritis | 1.100 | 4.5e-02 |
| ulcerative colitis | 2.000 | 2.2e-03 |
| Species | Source | Disease |
|---|---|---|
| OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| OMA EggNOG |
![Structure of compound 1 [PMID: 23589301]](/idg/api/v1/structure/3391bfb1-043d-473e-99c6-1c903773b0c4.svg)
compound 1 [PMID: 23589301]
- 7.10
trans-2-methylcrotonic acid
- 3.80
(S)-4-CMTB
- 6.40
CATPB
- 6.50
GLPG0974
pIC50 8.05
MLPDWKSSLILMAYIIIFLTGLPANLLALRAFVGRIRQPQPAPVHILLLSLTLADLLLLLLLPFKIIEAA 1 - 70 SNFRWYLPKVVCALTSFGFYSSIYCSTWLLAGISIERYLGVAFPVQYKLSRRPLYGVIAALVAWVMSFGH 71 - 140 CTIVIIVQYLNTTEQVRSGNEITCYENFTDNQLDVVLPVRLELCLVLFFIPMAVTIFCYWRFVWIMLSQP 141 - 210 LVGAQRRRRAVGLAVVTLLNFLVCFGPYNVSHLVGYHQRKSPWWRSIAVVFSSLNASLDPLLFYFSSSVV 211 - 280 RRAFGRGLQVLRNQGSSLLGRRGKDTAEGTNEDRGVGQGEGMPSSDFTTE 281 - 330 //
