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Protein

Free fatty acid receptor 1

Gene

Ffar1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.7 Publications

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei145Important for receptor activationBy similarity1
Sitei172Important for receptor activationBy similarity1
Binding sitei183AgonistBy similarity1
Binding sitei240AgonistBy similarity1
Binding sitei258AgonistBy similarity1

GO - Molecular functioni

  • bioactive lipid receptor activity Source: UniProtKB
  • lipid binding Source: UniProtKB-KW

GO - Biological processi

  • glucose homeostasis Source: UniProtKB
  • insulin secretion Source: MGI
  • positive regulation of calcium ion transport Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • response to fatty acid Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-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 1
Alternative name(s):
G-protein coupled receptor 40
Gene namesi
Name:Ffar1
Synonyms:Gpr40
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2684079. Ffar1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8ExtracellularSequence analysisBy similarity8
Transmembranei9 – 31Helical; Name=1Sequence analysisBy similarityAdd BLAST23
Topological domaini32 – 41CytoplasmicSequence analysisBy similarity10
Transmembranei42 – 64Helical; Name=2Sequence analysisBy similarityAdd BLAST23
Topological domaini65 – 79ExtracellularSequence analysisBy similarityAdd BLAST15
Transmembranei80 – 101Helical; Name=3Sequence analysisBy similarityAdd BLAST22
Topological domaini102 – 121CytoplasmicSequence analysisBy similarityAdd BLAST20
Transmembranei122 – 142Helical; Name=4Sequence analysisBy similarityAdd BLAST21
Topological domaini143 – 178ExtracellularSequence analysisBy similarityAdd BLAST36
Transmembranei179 – 200Helical; Name=5Sequence analysisBy similarityAdd BLAST22
Topological domaini201 – 223CytoplasmicSequence analysisBy similarityAdd BLAST23
Transmembranei224 – 248Helical; Name=6Sequence analysisBy similarityAdd BLAST25
Topological domaini249 – 256ExtracellularSequence analysisBy similarity8
Transmembranei257 – 279Helical; Name=7Sequence analysisBy similarityAdd BLAST23
Topological domaini280 – 300CytoplasmicSequence analysisBy similarityAdd BLAST21

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & 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

ChEMBLiCHEMBL5411.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002277551 – 300Free fatty acid receptor 1Add BLAST300

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi79 ↔ 170By similarity
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ76JU9.
PRIDEiQ76JU9.

PTM databases

iPTMnetiQ76JU9.
PhosphoSitePlusiQ76JU9.

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

BgeeiENSMUSG00000044453.
CleanExiMM_FFAR1.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000055564.

Chemistry databases

BindingDBiQ76JU9.

Structurei

3D structure databases

ProteinModelPortaliQ76JU9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni87 – 91Agonist bindingBy similarity5

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IV8D. Eukaryota.
ENOG4111572. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000236290.
HOVERGENiHBG080696.
InParanoidiQ76JU9.
KOiK04325.
OMAiLHLGCSD.
OrthoDBiEOG091G0HSS.
PhylomeDBiQ76JU9.
TreeFamiTF350010.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
IPR013313. GPR40_recept_FA.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01905. FATTYACIDR.
PR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q76JU9-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:300
Mass (Da):31,804
Last modified:July 5, 2004 - v1
Checksum:iD7FE133E510C399A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7L → F in AAN03478 (PubMed:12496284).Curated1

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.
CCDSiCCDS21113.1.
RefSeqiNP_918946.2. NM_194057.2.
UniGeneiMm.425422.

Genome annotation databases

EnsembliENSMUST00000052700; ENSMUSP00000055564; ENSMUSG00000044453.
GeneIDi233081.
KEGGimmu:233081.
UCSCiuc009ggq.1. mouse.

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.
CCDSiCCDS21113.1.
RefSeqiNP_918946.2. NM_194057.2.
UniGeneiMm.425422.

3D structure databases

ProteinModelPortaliQ76JU9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000055564.

Chemistry databases

BindingDBiQ76JU9.
ChEMBLiCHEMBL5411.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ76JU9.
PhosphoSitePlusiQ76JU9.

Proteomic databases

PaxDbiQ76JU9.
PRIDEiQ76JU9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052700; ENSMUSP00000055564; ENSMUSG00000044453.
GeneIDi233081.
KEGGimmu:233081.
UCSCiuc009ggq.1. mouse.

Organism-specific databases

CTDi2864.
MGIiMGI:2684079. Ffar1.

Phylogenomic databases

eggNOGiENOG410IV8D. Eukaryota.
ENOG4111572. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000236290.
HOVERGENiHBG080696.
InParanoidiQ76JU9.
KOiK04325.
OMAiLHLGCSD.
OrthoDBiEOG091G0HSS.
PhylomeDBiQ76JU9.
TreeFamiTF350010.

Enzyme and pathway databases

ReactomeiR-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

PROiQ76JU9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044453.
CleanExiMM_FFAR1.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
IPR013313. GPR40_recept_FA.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01905. FATTYACIDR.
PR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFFAR1_MOUSE
AccessioniPrimary (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: November 2, 2016
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.