UniProtKB - Q3UFD7 (FFAR3_MOUSE)
Protein
Free fatty acid receptor 3
Gene
Ffar3
Organism
Mus musculus (Mouse)
Status
Functioni
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).10 Publications
GO - Molecular functioni
- G protein-coupled receptor activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
GO - Biological processi
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Source: MGI
- cellular response to fatty acid Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- G protein-coupled receptor signaling pathway Source: UniProtKB
- inflammatory response Source: UniProtKB-KW
- mucosal immune response Source: UniProtKB
- negative regulation of blood pressure Source: UniProtKB
- positive regulation of action potential Source: MGI
- positive regulation of acute inflammatory response to non-antigenic stimulus Source: UniProtKB
- positive regulation of chemokine production Source: UniProtKB
- positive regulation of cytokine production involved in immune response Source: UniProtKB
- regulation of heart rate by chemical signal Source: MGI
- regulation of hormone biosynthetic process Source: UniProtKB
- regulation of insulin receptor signaling pathway Source: UniProtKB
- regulation of norepinephrine secretion Source: UniProtKB
- regulation of peptide hormone secretion Source: UniProtKB
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Biological process | Immunity, Inflammatory response |
Ligand | Lipid-binding |
Enzyme and pathway databases
Reactomei | R-MMU-416476, G alpha (q) signalling events R-MMU-444209, Free fatty acid receptors |
Names & Taxonomyi
Protein namesi | Recommended name: Free fatty acid receptor 3Alternative name(s): G-protein coupled receptor 41 |
Gene namesi | Name:Ffar3 Synonyms:Gm478, Gpr41 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2685324, Ffar3 |
Subcellular locationi
Plasma membrane
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 15 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 16 – 36 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 37 – 43 | CytoplasmicSequence analysis | 7 | |
Transmembranei | 44 – 64 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 65 – 98 | ExtracellularSequence analysisAdd BLAST | 34 | |
Transmembranei | 99 – 119 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 120 – 127 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 128 – 148 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 149 – 183 | ExtracellularSequence analysisAdd BLAST | 35 | |
Transmembranei | 184 – 206 | Helical; Name=5Sequence analysisAdd BLAST | 23 | |
Topological domaini | 207 – 218 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 219 – 239 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 240 – 254 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 255 – 275 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 276 – 319 | CytoplasmicSequence analysisAdd BLAST | 44 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Knockout mice display a retarded growth of sympathetic innervation and the superior cervical ganglion is significantly smaller. A heart rate decrease is also observed together with altered secretion of cardiac noradrenaline that might be due to reduced sympathetic nerve activity. Contrary to wild-type mice, oxygen consumption is not modified by feeding or starvation (PubMed:21518883). They also display impaired SCFA-triggered glucagon-like peptide 1/GLP-1 secretion and impaired glucose tolerance (PubMed:22190648). Finally, knockout mice display altered protective intestinal inflammatory and immune responses. Otherwise, they display normal growth and no major morphological abnormalities. Body weight, heart weight to body weight ratio, and metabolic parameters are comparable. However, there might be a gender bias, the effect on energy expenditure and body fat content being male specific (PubMed:23110765).5 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 154 | N → D: Loss of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3309101 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000227783 | 1 – 319 | Free fatty acid receptor 3Add BLAST | 319 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 84 ↔ 165 | PROSITE-ProRule annotation | ||
Glycosylationi | 154 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 162 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | Q3UFD7 |
PRIDEi | Q3UFD7 |
PTM databases
GlyGeni | Q3UFD7, 2 sites |
Expressioni
Tissue specificityi
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.5 Publications
Developmental stagei
Expressed in sympathetic ganglia and trunks at 13.5 dpc, 15.5 dpc and P1. Up-regulated during myocyte and adipocyte differentiation (at protein level).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000019429, Expressed in sympathetic ganglion and 27 other tissues |
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000092163 |
Chemistry databases
BindingDBi | Q3UFD7 |
Miscellaneous databases
RNActi | Q3UFD7, protein |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 213 – 218 | Poly-Arg | 6 |
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QQGM, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | Q3UFD7 |
OMAi | AYPLWYK |
OrthoDBi | 1129026at2759 |
PhylomeDBi | Q3UFD7 |
TreeFami | TF350010 |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR013312, GPR40-rel_orph |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01904, GPR40FAMILY |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
i Sequence
Sequence statusi: Complete.
Q3UFD7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGTSFFLGNY WLFFSVYLLV FLVGLPLNVM ALVVFVGKLR RRPVAVDLLL
60 70 80 90 100
LNLTISDLLL LLFLPFRMVE AACGMRWLLP FIFCPLSGFL FFTTIYLTSL
110 120 130 140 150
FLTAVSIERF LSVAYPLWYK TRPRLAQAGL VSVVCWFLAS AHCSVVYITE
160 170 180 190 200
YWGNATYSQG TNGTCYLEFR EDQLAILLPV RLEMAVVLFM VPLCITSYCY
210 220 230 240 250
SRLVWILSRG ASRRRRKRIM GLLAATLLIF FVCFGPYNMS HVVGYVSRES
260 270 280 290 300
PSWRSYVLLL STLNSCIDPL VFYFSSSKFQ ADFHQLLGRL LRTCVPWTQQ
310
VSLELKVKNG EEPSKECPS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK148616 mRNA Translation: BAE28624.1 |
CCDSi | CCDS21112.1 |
RefSeqi | NP_001028488.1, NM_001033316.2 |
Genome annotation databases
Ensembli | ENSMUST00000094583; ENSMUSP00000092163; ENSMUSG00000019429 ENSMUST00000185748; ENSMUSP00000140252; ENSMUSG00000019429 |
GeneIDi | 233080 |
KEGGi | mmu:233080 |
UCSCi | uc009ggp.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK148616 mRNA Translation: BAE28624.1 |
CCDSi | CCDS21112.1 |
RefSeqi | NP_001028488.1, NM_001033316.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000092163 |
Chemistry databases
BindingDBi | Q3UFD7 |
ChEMBLi | CHEMBL3309101 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | Q3UFD7, 2 sites |
Proteomic databases
PaxDbi | Q3UFD7 |
PRIDEi | Q3UFD7 |
Genome annotation databases
Ensembli | ENSMUST00000094583; ENSMUSP00000092163; ENSMUSG00000019429 ENSMUST00000185748; ENSMUSP00000140252; ENSMUSG00000019429 |
GeneIDi | 233080 |
KEGGi | mmu:233080 |
UCSCi | uc009ggp.1, mouse |
Organism-specific databases
CTDi | 2865 |
MGIi | MGI:2685324, Ffar3 |
Phylogenomic databases
eggNOGi | ENOG502QQGM, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | Q3UFD7 |
OMAi | AYPLWYK |
OrthoDBi | 1129026at2759 |
PhylomeDBi | Q3UFD7 |
TreeFami | TF350010 |
Enzyme and pathway databases
Reactomei | R-MMU-416476, G alpha (q) signalling events R-MMU-444209, Free fatty acid receptors |
Miscellaneous databases
BioGRID-ORCSi | 233080, 0 hits in 17 CRISPR screens |
PROi | PR:Q3UFD7 |
RNActi | Q3UFD7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000019429, Expressed in sympathetic ganglion and 27 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR013312, GPR40-rel_orph |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01904, GPR40FAMILY |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FFAR3_MOUSE | |
Accessioni | Q3UFD7Primary (citable) accession number: Q3UFD7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 21, 2006 |
Last sequence update: | October 11, 2005 | |
Last modified: | December 2, 2020 | |
This is version 104 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries