BioPAX pathway converted from "Receptor FFAR2 binds carboxylates" in the Reactome database.Receptor FFAR2 binds carboxylatesReceptor FFAR2 binds carboxylatesFree fatty acid receptor 2 (FFAR2/GPR43) is activated by carboxylate ligands, with relative potencies as follows: acetate = propionate = butyrate > pentanoate > hexanoate = formate.Authored: Jupe, S, 2009-10-19Reviewed: D'Eustachio, P, 2009-12-11Edited: Jupe, S, 2010-03-01Converted from EntitySet in ReactomeReactome DB_ID: 4442101extracellular regionGO0005576FFAR2 ligands [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityHCOOH [extracellular region]Valerate [extracellular region]CH3COO- [extracellular region]HXA [extracellular region]EtCOO- or C2H5COO- [extracellular region]BUT [extracellular region]Reactomehttp://www.reactome.orgChEBI30751ChEBI31011ChEBI15366ChEBI17120ChEBI30768ChEBI30772Reactome DB_ID: 4439441plasma membraneGO0005886UniProt:O15552 FFAR2FFAR2FFA2GPR43GPCR43FFAR2FUNCTION 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).SUBUNIT Interacts with FCN1 (via Fibrinogen C-terminal domain).TISSUE SPECIFICITY Expressed at relatively high levels in peripheral blood leukocytes and, to lesser extent, in spleen.SIMILARITY Belongs to the G-protein coupled receptor 1 family.Homo sapiensNCBI Taxonomy9606UniProtO15552Chain Coordinates1EQUAL330EQUALReactome DB_ID: 4441741FFAR2:FFAR2 ligands [plasma membrane]FFAR2:FFAR2 ligandsConverted from EntitySet in ReactomeReactome DB_ID: 4442101Reactome DB_ID: 44394411EQUAL330EQUALReactome Database ID Release 75444174Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444174ReactomeR-HSA-4441742Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444174.2Reactome Database ID Release 75444171Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444171ReactomeR-HSA-4441711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444171.112496283Pubmed2003The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acidsBrown, AJGoldsworthy, SMBarnes, AAEilert, MMTcheang, LDaniels, DMuir, AIWigglesworth, MJKinghorn, IFraser, NJPike, NBStrum, JCSteplewski, KMMurdock, PRHolder, JCMarshall, FHSzekeres, PGWilson, SIgnar, DMFoord, SMWise, ADowell, SJJ Biol Chem 278:11312-9