UniProtKB - Q76JU9 (FFAR1_MOUSE)
Protein
Free fatty acid receptor 1
Gene
Ffar1
Organism
Mus musculus (Mouse)
Status
Functioni
G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (PubMed:23335512). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway. Mediates the anti-inflammatory effects of omega-3 polyunsaturated fatty acids (PUFAs) via inhibition of NLRP3 inflammasome activation.By similarity7 Publications
Activity regulationi
Is also activated by synthetic agonists, such as AM-8182, AM-6331 and TAK-875 (fasiglifam). AM-8182 is a full agonist, while AM-6331 and TAK-875 (fasiglifam) are partial agonists that potentiate the activity of the endogenous ligands, such as alpha-linolenic acid and gamma-linolenic acid.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 145 | Important for receptor activationBy similarity | 1 | |
Sitei | 172 | Important for receptor activationBy similarity | 1 | |
Binding sitei | 183 | AgonistBy similarity | 1 | |
Binding sitei | 240 | AgonistBy similarity | 1 | |
Binding sitei | 258 | AgonistBy similarity | 1 |
GO - Molecular functioni
- bioactive lipid receptor activity Source: UniProtKB
- fatty acid binding Source: MGI
GO - Biological processi
- glucose homeostasis Source: UniProtKB
- G protein-coupled receptor signaling pathway Source: MGI
- insulin secretion Source: MGI
- negative regulation of interleukin-1 beta production Source: MGI
- positive regulation of calcium ion transport Source: UniProtKB
- positive regulation of calcium ion transport into cytosol Source: MGI
- positive regulation of cytosolic calcium ion concentration Source: UniProtKB
- positive regulation of insulin secretion Source: UniProtKB
- response to fatty acid Source: UniProtKB
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Ligand | Lipid-binding |
Enzyme and pathway databases
Reactomei | R-MMU-381771, Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) R-MMU-400511, Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) R-MMU-416476, G alpha (q) signalling events R-MMU-434316, Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion R-MMU-444209, Free fatty acid receptors |
Names & Taxonomyi
Protein namesi | Recommended name: Free fatty acid receptor 1Alternative name(s): G-protein coupled receptor 40 |
Gene namesi | Name:Ffar1 Synonyms:Gpr40 |
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:2684079, Ffar1 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein Sequence analysis
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 8 | ExtracellularSequence analysisBy similarity | 8 | |
Transmembranei | 9 – 31 | Helical; Name=1Sequence analysisBy similarityAdd BLAST | 23 | |
Topological domaini | 32 – 41 | CytoplasmicSequence analysisBy similarity | 10 | |
Transmembranei | 42 – 64 | Helical; Name=2Sequence analysisBy similarityAdd BLAST | 23 | |
Topological domaini | 65 – 79 | ExtracellularSequence analysisBy similarityAdd BLAST | 15 | |
Transmembranei | 80 – 101 | Helical; Name=3Sequence analysisBy similarityAdd BLAST | 22 | |
Topological domaini | 102 – 121 | CytoplasmicSequence analysisBy similarityAdd BLAST | 20 | |
Transmembranei | 122 – 142 | Helical; Name=4Sequence analysisBy similarityAdd BLAST | 21 | |
Topological domaini | 143 – 178 | ExtracellularSequence analysisBy similarityAdd BLAST | 36 | |
Transmembranei | 179 – 200 | Helical; Name=5Sequence analysisBy similarityAdd BLAST | 22 | |
Topological domaini | 201 – 223 | CytoplasmicSequence analysisBy similarityAdd BLAST | 23 | |
Transmembranei | 224 – 248 | Helical; Name=6Sequence analysisBy similarityAdd BLAST | 25 | |
Topological domaini | 249 – 256 | ExtracellularSequence analysisBy similarity | 8 | |
Transmembranei | 257 – 279 | Helical; Name=7Sequence analysisBy similarityAdd BLAST | 23 | |
Topological domaini | 280 – 300 | CytoplasmicSequence analysisBy similarityAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
No visible phenotype at birth and during the following six weeks. Male mice tend to develop a slightly decreased glucose tolerance after 13 weeks of age, but this is not observed with female mice. Insulin secretion in response to glucose is unchanged in mutant mice, but it is not potentiated by fatty acids, contrary to what is observed with wild-type mice. On the other hand, wild-type and mutant mice display the same inhibition of the first phase of glucose-stimulated insulin secretion after prolonged exposure to fatty acids or exposure to a high-fat diet (PubMed:17395749 and PubMed:18559658). Compared to wild-type, mutant mice that are kept on a high-fat diet display a decrease of the second phase of glucose-stimulated insulin secretion (PubMed:18559658). Mutant mice do not display increased secretion of glucagon-like peptide 1 (GLP-1) in response to oral absorption of corn oil and display slightly increased blood glucose levels after oral absorption of corn oil (PubMed:23403053). Besides, mutant mice display decreased bone density (PubMed:23335512).4 Publications
Chemistry databases
ChEMBLi | CHEMBL5411 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000227755 | 1 – 300 | Free fatty acid receptor 1Add BLAST | 300 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 79 ↔ 170 | By similarity | ||
Glycosylationi | 153 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | Q76JU9 |
PRIDEi | Q76JU9 |
PTM databases
GlyGeni | Q76JU9, 1 site |
iPTMneti | Q76JU9 |
PhosphoSitePlusi | Q76JU9 |
Expressioni
Tissue specificityi
Expressed in pancreatic islet beta cells (at protein level) (PubMed:16044321). Expressed in pancreatic islet beta cells.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000044453, Expressed in spleen and 22 other tissues |
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000055564 |
Chemistry databases
BindingDBi | Q76JU9 |
Miscellaneous databases
RNActi | Q76JU9, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 87 – 91 | Agonist bindingBy similarity | 5 |
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QVCS, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | Q76JU9 |
OMAi | RRPRYSW |
OrthoDBi | 1074213at2759 |
PhylomeDBi | Q76JU9 |
TreeFami | TF350010 |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR013312, GPR40-rel_orph IPR013313, GPR40_recept_FA |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR01905, FATTYACIDR PR00237, GPCRRHODOPSN PR01904, GPR40FAMILY |
PROSITEi | View protein in PROSITE PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
i Sequence
Sequence statusi: Complete.
Q76JU9-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDLPPQLSFA LYVSAFALGF PLNLLAIRGA VSHAKLRLTP SLVYTLHLGC
60 70 80 90 100
SDLLLAITLP LKAVEALASG AWPLPLPFCP VFALAHFAPL YAGGGFLAAL
110 120 130 140 150
SAGRYLGAAF PFGYQAIRRP RYSWGVCVAI WALVLCHLGL ALGLETSGSW
160 170 180 190 200
LDNSTSSLGI NIPVNGSPVC LEAWDPDSAR PARLSFSILL FFLPLVITAF
210 220 230 240 250
CYVGCLRALV RSGLSHKRKL RAAWVAGGAL LTLLLCLGPY NASNVASFIN
260 270 280 290 300
PDLGGSWRKL GLITGAWSVV LNPLVTGYLG TGPGRGTICV TRTQRGTIQK
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 7 | L → F in AAN03478 (PubMed:12496284).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF539809 Genomic DNA Translation: AAN03478.1 AB095745 mRNA Translation: BAC82555.1 BC132014 mRNA Translation: AAI32015.1 BC138099 mRNA Translation: AAI38100.1 |
CCDSi | CCDS21113.1 |
RefSeqi | NP_918946.2, NM_194057.2 |
Genome annotation databases
Ensembli | ENSMUST00000052700; ENSMUSP00000055564; ENSMUSG00000044453 |
GeneIDi | 233081 |
KEGGi | mmu:233081 |
UCSCi | uc009ggq.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF539809 Genomic DNA Translation: AAN03478.1 AB095745 mRNA Translation: BAC82555.1 BC132014 mRNA Translation: AAI32015.1 BC138099 mRNA Translation: AAI38100.1 |
CCDSi | CCDS21113.1 |
RefSeqi | NP_918946.2, NM_194057.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000055564 |
Chemistry databases
BindingDBi | Q76JU9 |
ChEMBLi | CHEMBL5411 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | Q76JU9, 1 site |
iPTMneti | Q76JU9 |
PhosphoSitePlusi | Q76JU9 |
Proteomic databases
PaxDbi | Q76JU9 |
PRIDEi | Q76JU9 |
Protocols and materials databases
Antibodypediai | 15908, 321 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000052700; ENSMUSP00000055564; ENSMUSG00000044453 |
GeneIDi | 233081 |
KEGGi | mmu:233081 |
UCSCi | uc009ggq.1, mouse |
Organism-specific databases
CTDi | 2864 |
MGIi | MGI:2684079, Ffar1 |
Phylogenomic databases
eggNOGi | ENOG502QVCS, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | Q76JU9 |
OMAi | RRPRYSW |
OrthoDBi | 1074213at2759 |
PhylomeDBi | Q76JU9 |
TreeFami | TF350010 |
Enzyme and pathway databases
Reactomei | R-MMU-381771, Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) R-MMU-400511, Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) R-MMU-416476, G alpha (q) signalling events R-MMU-434316, Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion R-MMU-444209, Free fatty acid receptors |
Miscellaneous databases
BioGRID-ORCSi | 233081, 3 hits in 17 CRISPR screens |
PROi | PR:Q76JU9 |
RNActi | Q76JU9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000044453, Expressed in spleen and 22 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR013312, GPR40-rel_orph IPR013313, GPR40_recept_FA |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR01905, FATTYACIDR PR00237, GPCRRHODOPSN PR01904, GPR40FAMILY |
PROSITEi | View protein in PROSITE PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FFAR1_MOUSE | |
Accessioni | Q76JU9Primary (citable) accession number: Q76JU9 Secondary accession number(s): A2RS88, Q8K3T5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 21, 2006 |
Last sequence update: | July 5, 2004 | |
Last modified: | December 2, 2020 | |
This is version 118 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