UniProtKB - Q8VCK6 (FFAR2_MOUSE)
Protein
Free fatty acid receptor 2
Gene
Ffar2
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 but also to the Gq family (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 (PubMed:22190648, PubMed:23589301). May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake (PubMed:20399779). Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes (PubMed:16123168, PubMed:23589301). 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 (PubMed:23665276). May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils (PubMed:19917676, PubMed:19865172). 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.9 Publications
GO - Molecular functioni
- G protein-coupled receptor activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
GO - Biological processi
- cell surface pattern recognition receptor signaling pathway Source: UniProtKB
- cellular response to fatty acid Source: UniProtKB
- fat cell differentiation Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- G protein-coupled receptor signaling pathway Source: UniProtKB
- leukocyte chemotaxis involved in inflammatory response Source: UniProtKB
- lipid storage Source: UniProtKB
- mucosal immune response Source: UniProtKB
- 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
- positive regulation of interleukin-8 production Source: UniProtKB
- regulation of acute inflammatory response 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 2Alternative name(s): G-protein coupled receptor 43 Leukocyte-specific STAT-induced GPCR |
Gene namesi | Name:Ffar2 Synonyms:Gpr43, Lssig |
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:2441731, Ffar2 |
Subcellular locationi
Plasma membrane
- Cell membrane Curated; Multi-pass membrane protein Curated
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cell projection Source: MGI
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 8 | ExtracellularSequence analysis | 8 | |
Transmembranei | 9 – 29 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 30 – 43 | CytoplasmicSequence analysisAdd BLAST | 14 | |
Transmembranei | 44 – 64 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 65 – 79 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 80 – 100 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 101 – 126 | CytoplasmicSequence analysisAdd BLAST | 26 | |
Transmembranei | 127 – 147 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 148 – 184 | ExtracellularSequence analysisAdd BLAST | 37 | |
Transmembranei | 185 – 205 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 206 – 219 | CytoplasmicSequence analysisAdd BLAST | 14 | |
Transmembranei | 220 – 240 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 241 – 255 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 256 – 276 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 277 – 330 | CytoplasmicSequence analysisAdd BLAST | 54 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Knockout mice display altered protective intestinal inflammatory and immune responses but no gross developmental defects.3 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 159 | E → G: Gain of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3309047 |
GuidetoPHARMACOLOGYi | 226 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000228144 | 1 – 330 | Free fatty acid receptor 2Add BLAST | 330 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 151 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 167 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
PaxDbi | Q8VCK6 |
PRIDEi | Q8VCK6 |
PTM databases
GlyGeni | Q8VCK6, 2 sites |
iPTMneti | Q8VCK6 |
PhosphoSitePlusi | Q8VCK6 |
Expressioni
Tissue specificityi
Highly expressed in hematopoietic tissues, such as spleen and bone marrow, with highest levels in a subset of immune cells, including monocytes or neutrophils. Expressed in adipose tissues with high expression in differentiating adipocytes. Expressed by intestinal endocrine cells.3 Publications
Inductioni
During differentiation of leukocytes. This induction is STAT3-dependent. Up-regulated in adipose tissues by high-fat diet.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000051314, Expressed in dorsal pancreas and 118 other tissues |
Genevisiblei | Q8VCK6, MM |
Interactioni
Subunit structurei
Interacts with FCN1 (via Fibrinogen C-terminal domain).
By similarityProtein-protein interaction databases
STRINGi | 10090.ENSMUSP00000052600 |
Chemistry databases
BindingDBi | Q8VCK6 |
Miscellaneous databases
RNActi | Q8VCK6, protein |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 216 – 219 | Poly-Arg | 4 |
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 | Q8VCK6 |
OMAi | WVMSFGH |
OrthoDBi | 1129026at2759 |
PhylomeDBi | Q8VCK6 |
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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q8VCK6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTPDWHSSLI LTAYILIFLT GLPANLLALR AFMGRVRQPQ PAPVHILLLN
60 70 80 90 100
LTLADLLLLL LLPFRIVEAA SNFRWYLPKI VCALTGFGFY SSIYCSTWLL
110 120 130 140 150
AGISMERYLG VAFPVQYKLS RRPLYGVIAA LVAWIMSFGH CTIVIIVQYL
160 170 180 190 200
NSTEQVGTEN QITCYENFTQ EQLDVVLPVR LELCLVLFFV PMAVTIFCYW
210 220 230 240 250
RFVWIMLTQP HVGAQRRRRA VGLAVVTLLN FLVCFGPYNM SHLVGFYLRQ
260 270 280 290 300
SPSWRVEAVV FSSLNASLDP LLFYFSSSVV RRAFGKGLLL IRNPASSMLG
310 320 330
RGAKETVEGT KMDRGGSQAE GVQSSEFVTE
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WR60 | A0A087WR60_MOUSE | Free fatty acid receptor 2 | Ffar2 | 133 | Annotation score: | ||
A0A087WQJ1 | A0A087WQJ1_MOUSE | Free fatty acid receptor 2 | Ffar2 | 142 | Annotation score: | ||
A0A087WR67 | A0A087WR67_MOUSE | Free fatty acid receptor 2 | Ffar2 | 182 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF545043 mRNA Translation: AAO16236.1 AK078861 mRNA Translation: BAC37425.1 BC019570 mRNA Translation: AAH19570.1 |
CCDSi | CCDS21111.1 |
RefSeqi | NP_001161981.1, NM_001168509.1 NP_001161982.1, NM_001168510.1 NP_001161983.1, NM_001168511.1 NP_001161984.1, NM_001168512.1 NP_666299.1, NM_146187.4 XP_011248850.1, XM_011250548.2 XP_011248851.1, XM_011250549.2 XP_011248854.1, XM_011250552.2 XP_011248855.1, XM_011250553.2 XP_011248856.1, XM_011250554.2 |
Genome annotation databases
Ensembli | ENSMUST00000053156; ENSMUSP00000052600; ENSMUSG00000051314 ENSMUST00000163504; ENSMUSP00000127758; ENSMUSG00000051314 ENSMUST00000168528; ENSMUSP00000129398; ENSMUSG00000051314 |
GeneIDi | 233079 |
KEGGi | mmu:233079 |
UCSCi | uc009ggn.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF545043 mRNA Translation: AAO16236.1 AK078861 mRNA Translation: BAC37425.1 BC019570 mRNA Translation: AAH19570.1 |
CCDSi | CCDS21111.1 |
RefSeqi | NP_001161981.1, NM_001168509.1 NP_001161982.1, NM_001168510.1 NP_001161983.1, NM_001168511.1 NP_001161984.1, NM_001168512.1 NP_666299.1, NM_146187.4 XP_011248850.1, XM_011250548.2 XP_011248851.1, XM_011250549.2 XP_011248854.1, XM_011250552.2 XP_011248855.1, XM_011250553.2 XP_011248856.1, XM_011250554.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000052600 |
Chemistry databases
BindingDBi | Q8VCK6 |
ChEMBLi | CHEMBL3309047 |
GuidetoPHARMACOLOGYi | 226 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | Q8VCK6, 2 sites |
iPTMneti | Q8VCK6 |
PhosphoSitePlusi | Q8VCK6 |
Proteomic databases
PaxDbi | Q8VCK6 |
PRIDEi | Q8VCK6 |
Protocols and materials databases
Antibodypediai | 15916, 326 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000053156; ENSMUSP00000052600; ENSMUSG00000051314 ENSMUST00000163504; ENSMUSP00000127758; ENSMUSG00000051314 ENSMUST00000168528; ENSMUSP00000129398; ENSMUSG00000051314 |
GeneIDi | 233079 |
KEGGi | mmu:233079 |
UCSCi | uc009ggn.1, mouse |
Organism-specific databases
CTDi | 2867 |
MGIi | MGI:2441731, Ffar2 |
Phylogenomic databases
eggNOGi | ENOG502QQGM, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | Q8VCK6 |
OMAi | WVMSFGH |
OrthoDBi | 1129026at2759 |
PhylomeDBi | Q8VCK6 |
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 | 233079, 1 hit in 18 CRISPR screens |
ChiTaRSi | Ffar2, mouse |
PROi | PR:Q8VCK6 |
RNActi | Q8VCK6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000051314, Expressed in dorsal pancreas and 118 other tissues |
Genevisiblei | Q8VCK6, MM |
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 | FFAR2_MOUSE | |
Accessioni | Q8VCK6Primary (citable) accession number: Q8VCK6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 21, 2006 |
Last sequence update: | March 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 131 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