LMPD Database

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LMP004490

UniProt Annotations

Entry Information
Gene Namefree fatty acid receptor 2
Protein EntryFFAR2_MOUSE
UniProt IDQ8VCK6
SpeciesMouse
Comments
Comment typeDescription
Disruption PhenotypeKnockout mice display altered protective intestinal inflammatory and immune responses but no gross developmental defects. {ECO:0000269|PubMed:18499755, ECO:0000269|PubMed:19865172, ECO:0000269|PubMed:23665276}.
FunctionG 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: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 (PubMed:22190648, PubMed:23589301). May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake (PubMed:20399779). Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes (PubMed:16123168, PubMed:23589301). 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 (PubMed:23665276). May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils (PubMed:19917676, PubMed:19865172). 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. {ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:16123168, ECO:0000269|PubMed:18499755, ECO:0000269|PubMed:19865172, ECO:0000269|PubMed:19917676, ECO:0000269|PubMed:20399779, ECO:0000269|PubMed:22190648, ECO:0000269|PubMed:23589301, ECO:0000269|PubMed:23665276}.
InductionDuring differentiation of leukocytes. This induction is STAT3-dependent. Up-regulated in adipose tissues by high-fat diet. {ECO:0000269|PubMed:12393494, ECO:0000269|PubMed:16123168}.
SimilarityBelongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular LocationCell membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
SubunitInteracts with FCN1 (via Fibrinogen C-terminal domain). {ECO:0000250}.
Tissue SpecificityHighly expressed in hematopoietic tissues, such as spleen and bone marrow, with highest levels in a subset of immune cells, including monocytes or neutrophils. Expressed in adipose tissues with high expression in differentiating adipocytes. Expressed by intestinal endocrine cells. {ECO:0000269|PubMed:12393494, ECO:0000269|PubMed:16123168, ECO:0000269|PubMed:22190648}.