NameFree fatty acid receptor 2
Synonyms
  • FFA2
  • G-protein coupled receptor 43
  • GPCR43
  • GPR43
Gene NameFFAR2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0013914|Free fatty acid receptor 2
MLPDWKSSLILMAYIIIFLTGLPANLLALRAFVGRIRQPQPAPVHILLLSLTLADLLLLL
LLPFKIIEAASNFRWYLPKVVCALTSFGFYSSIYCSTWLLAGISIERYLGVAFPVQYKLS
RRPLYGVIAALVAWVMSFGHCTIVIIVQYLNTTEQVRSGNEITCYENFTDNQLDVVLPVR
LELCLVLFFIPMAVTIFCYWRFVWIMLSQPLVGAQRRRRAVGLAVVTLLNFLVCFGPYNV
SHLVGYHQRKSPWWRSIAVVFSSLNASLDPLLFYFSSSVVRRAFGRGLQVLRNQGSSLLG
RRGKDTAEGTNEDRGVGQGEGMPSSDFTTE
Number of residues330
Molecular Weight37143.375
Theoretical pINot Available
GO Classification
Functions
  • G-protein coupled receptor activity
  • lipid binding
Processes
  • regulation of peptide hormone secretion
  • glucose homeostasis
  • G-protein coupled receptor signaling pathway
  • positive regulation of chemokine production
  • positive regulation of interleukin-8 secretion
  • cellular response to fatty acid
  • cell surface pattern recognition receptor signaling pathway
  • fat cell differentiation
  • leukocyte chemotaxis involved in inflammatory response
  • lipid storage
  • mucosal immune response
  • positive regulation of acute inflammatory response to non-antigenic stimulus
  • positive regulation of cytokine production involved in immune response
  • regulation of acute inflammatory response
Components
  • plasma membrane
  • integral component of plasma membrane
  • cell projection
General FunctionLipid binding
Specific 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: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).
Pfam Domain Function
Transmembrane Regions13-33 42-62 85-105 127-147 174-194 220-240 256-276
GenBank Protein IDNot Available
UniProtKB IDO15552
UniProtKB Entry NameFFAR2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0013915|Free fatty acid receptor 2 (FFAR2)
ATGCTGCCGGACTGGAAGAGCTCCTTGATCCTCATGGCTTACATCATCATCTTCCTCACT
GGCCTCCCTGCCAACCTCCTGGCCCTGCGGGCCTTTGTGGGGCGGATCCGCCAGCCCCAG
CCTGCACCTGTGCACATCCTCCTGCTGAGCCTGACGCTGGCCGACCTCCTCCTGCTGCTG
CTGCTGCCCTTCAAGATCATCGAGGCTGCGTCGAACTTCCGCTGGTACCTGCCCAAGGTC
GTCTGCGCCCTCACGAGTTTTGGCTTCTACAGCAGCATCTACTGCAGCACGTGGCTCCTG
GCGGGCATCAGCATCGAGCGCTACCTGGGAGTGGCTTTCCCCGTGCAGTACAAGCTCTCC
CGCCGGCCTCTGTATGGAGTGATTGCAGCTCTGGTGGCCTGGGTTATGTCCTTTGGTCAC
TGCACCATCGTGATCATCGTTCAATACTTGAACACGACTGAGCAGGTCAGAAGTGGCAAT
GAAATTACCTGCTACGAGAACTTCACCGATAACCAGTTGGACGTGGTGCTGCCCGTGCGG
CTGGAGCTGTGCCTGGTGCTCTTCTTCATCCCCATGGCAGTCACCATCTTCTGCTACTGG
CGTTTTGTGTGGATCATGCTCTCCCAGCCCCTTGTGGGGGCCCAGAGGCGGCGCCGAGCC
GTGGGGCTGGCTGTGGTGACGCTGCTCAATTTCCTGGTGTGCTTCGGACCTTACAACGTG
TCCCACCTGGTGGGGTATCACCAGAGAAAAAGCCCCTGGTGGCGGTCAATAGCCGTGGTG
TTCAGTTCACTCAACGCCAGTCTGGACCCCCTGCTCTTCTATTTCTCTTCTTCAGTGGTG
CGCAGGGCATTTGGGAGAGGGCTGCAGGTGCTGCGGAATCAGGGCTCCTCCCTGTTGGGA
CGCAGAGGCAAAGACACAGCAGAGGGGACAAATGAGGACAGGGGTGTGGGTCAAGGAGAA
GGGATGCCAAGTTCGGACTTCACTACAGAGTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:4501
Chromosome Location19
LocusNot Available
References
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  7. Stoddart LA, Smith NJ, Jenkins L, Brown AJ, Milligan G: Conserved polar residues in transmembrane domains V, VI, and VII of free fatty acid receptor 2 and free fatty acid receptor 3 are required for the binding and function of short chain fatty acids. J Biol Chem. 2008 Nov 21;283(47):32913-24. doi: 10.1074/jbc.M805601200. Epub 2008 Sep 18. 18801738
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  9. Zhang J, Yang L, Ang Z, Yoong SL, Tran TT, Anand GS, Tan NS, Ho B, Ding JL: Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense. J Immunol. 2010 Dec 1;185(11):6899-910. doi: 10.4049/jimmunol.1001225. Epub 2010 Oct 29. 21037097
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