InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ffar3

Summary

InnateDB Protein

IDBP-171531.6

Last Modified

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

Gene Symbol

Ffar3

Protein Name

free fatty acid receptor 3

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000092163

InnateDB Gene

IDBG-171529 (Ffar3)

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. 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. Activated by SCFAs and by beta-hydroxybutyrate, a ketone body produced by the liver upon starvation, it inhibits N-type calcium channels and modulates the activity of sympathetic neurons through a signaling cascade involving the beta and gamma subunits of its coupled G protein, phospholipase C and MAP kinases. Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate (PubMed:21518883, PubMed:22673524). Upon activation by SCFAs accumulating in the intestine, it may also signal to the brain via neural circuits which in turn would regulate intestinal gluconeogenesis. May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion (PubMed:23401498). May also regulate secretion of the PYY peptide by enteroendocrine cells and control gut motility, intestinal transit rate, and the harvesting of energy from SCFAs produced by gut microbiota (PubMed:18931303). May also indirectly regulate the production of LEP/Leptin, a hormone acting on the CNS to inhibit food intake, in response to the presence of short-chain fatty acids in the intestine (PubMed:14722361, PubMed:20399779). Finally, may also play a role in glucose homeostasis (PubMed:22190648, PubMed:24748202). Besides its role in energy homeostasis, may play a role in intestinal immunity. May mediate the activation of the inflammatory and immune response by SCFAs in the gut, regulating the rapid production of chemokines and cytokines by intestinal epithelial cells (PubMed:23665276). Exhibits an SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016). {ECO:0000269PubMed:14722361, ECO:0000269PubMed:18931303, ECO:0000269PubMed:20399779, ECO:0000269PubMed:21518883, ECO:0000269PubMed:22190648, ECO:0000269PubMed:22673524, ECO:0000269PubMed:23066016, ECO:0000269PubMed:23401498, ECO:0000269PubMed:23665276, ECO:0000269PubMed:24748202}.

Subcellular Localization

Cell membrane; Multi-pass membrane protein.

Disease Associations

Tissue Specificity

Expressed in white adipose tissue and skeletal muscle (at protein level). Abundantly expressed in sympathetic ganglia such as the superior cervical ganglion. Also expressed by intestinal endocrine cells. {ECO:0000269PubMed:14722361, ECO:0000269PubMed:18931303, ECO:0000269PubMed:21518883, ECO:0000269PubMed:22190648, ECO:0000269PubMed:24748202}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.

Gene Ontology

Molecular Function

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

Biological Process

GO:0003062	regulation of heart rate by chemical signal
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007193	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
GO:0045760	positive regulation of action potential
GO:0071398	cellular response to fatty acid