InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FFAR2

Summary

InnateDB Protein

IDBP-44262.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FFAR2

Protein Name

free fatty acid receptor 2

Synonyms

FFA2R; GPR43;

Species

Homo sapiens

Ensembl Protein

ENSP00000246549

InnateDB Gene

IDBG-44260 (FFAR2)

Protein Structure

UniProt Annotation

Function

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). {ECO:0000269PubMed:12496283, ECO:0000269PubMed:12684041, ECO:0000269PubMed:12711604, ECO:0000269PubMed:18801738, ECO:0000269PubMed:21037097, ECO:0000269PubMed:23066016, ECO:0000269PubMed:23589301}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:18801738}; Multi-pass membrane protein {ECO:0000269PubMed:18801738}.

Disease Associations

Tissue Specificity

Expressed at relatively high levels in peripheral blood leukocytes and, to lesser extent, in spleen. {ECO:0000269PubMed:12496283, ECO:0000269PubMed:12684041}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004930	G-protein coupled receptor activity
GO:0008289	lipid binding

Biological Process

GO:0007186	G-protein coupled receptor signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0071398	cellular response to fatty acid

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000276 G protein-coupled receptor, rhodopsin-like
IPR013312 G protein-coupled receptor 40-related receptor
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019426 7TM GPCR, serpentine receptor class v (Srv)

PFAM

PF00001
PF10323

PRINTS

PR00237
PR01904

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O15552