UniProtKB - O15552 (FFAR2_HUMAN)
Protein
Free fatty acid receptor 2
Gene
FFAR2
Organism
Homo sapiens (Human)
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:12496283, PubMed:12711604, 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. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. 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. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. 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 (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).7 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
PathwayCommonsi | O15552 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-444209, Free fatty acid receptors |
SIGNORi | O15552 |
Chemistry databases
SwissLipidsi | SLP:000001558 |
Names & Taxonomyi
Protein namesi | Recommended name: Free fatty acid receptor 2Alternative name(s): G-protein coupled receptor 43 |
Gene namesi | Name:FFAR2 Synonyms:FFA2, GPCR43, GPR43 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000126262.4 |
HGNCi | HGNC:4501, FFAR2 |
MIMi | 603823, gene |
neXtProti | NX_O15552 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma Membrane
- integral component of plasma membrane Source: ProtInc
- plasma membrane Source: UniProtKB
Other locations
- cell projection Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 12 | ExtracellularSequence analysisAdd BLAST | 12 | |
Transmembranei | 13 – 33 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 34 – 41 | Cytoplasmic | 8 | |
Transmembranei | 42 – 62 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 63 – 84 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 85 – 105 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 106 – 126 | CytoplasmicSequence analysisAdd BLAST | 21 | |
Transmembranei | 127 – 147 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 148 – 173 | ExtracellularSequence analysisAdd BLAST | 26 | |
Transmembranei | 174 – 194 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 195 – 219 | CytoplasmicSequence analysisAdd BLAST | 25 | |
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
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 90 | Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 2 Publications | 1 | |
Mutagenesisi | 90 | Y → W: Complete loss of acetate-induced G protein-coupled receptor activity. 2 Publications | 1 | |
Mutagenesisi | 106 | E → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 108 | Y → A: Complete loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 140 | H → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 2 Publications | 1 | |
Mutagenesisi | 148 | Q → A: No effect on SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 148 | Q → E: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 159 | G → E: Partial loss of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 165 | Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 180 | R → A, K, L or S: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications | 1 | |
Mutagenesisi | 238 | Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 239 | N → A: Complete loss of acetate-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 242 | H → A or F: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications | 1 | |
Mutagenesisi | 255 | R → A: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications | 1 |
Organism-specific databases
DisGeNETi | 2867 |
OpenTargetsi | ENSG00000126262 |
PharmGKBi | PA28890 |
Miscellaneous databases
Pharosi | O15552, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5493 |
DrugCentrali | O15552 |
GuidetoPHARMACOLOGYi | 226 |
Polymorphism and mutation databases
BioMutai | FFAR2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069571 | 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 | O15552 |
PeptideAtlasi | O15552 |
PRIDEi | O15552 |
ProteomicsDBi | 48754 |
PTM databases
GlyGeni | O15552, 2 sites |
iPTMneti | O15552 |
PhosphoSitePlusi | O15552 |
Expressioni
Tissue specificityi
Expressed at relatively high levels in peripheral blood leukocytes and, to lesser extent, in spleen.2 Publications
Gene expression databases
Bgeei | ENSG00000126262, Expressed in blood and 114 other tissues |
ExpressionAtlasi | O15552, baseline and differential |
Genevisiblei | O15552, HS |
Organism-specific databases
HPAi | ENSG00000126262, Tissue enhanced (blood, lymphoid tissue) |
Interactioni
Subunit structurei
Interacts with FCN1 (via Fibrinogen C-terminal domain).
1 PublicationBinary interactionsi
O15552
Protein-protein interaction databases
BioGRIDi | 109125, 108 interactors |
IntActi | O15552, 106 interactors |
STRINGi | 9606.ENSP00000473159 |
Chemistry databases
BindingDBi | O15552 |
Miscellaneous databases
RNActi | O15552, protein |
Family & Domainsi
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 | O15552 |
OMAi | WVMSFGH |
OrthoDBi | 1129026at2759 |
PhylomeDBi | O15552 |
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.
O15552-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLPDWKSSLI LMAYIIIFLT GLPANLLALR AFVGRIRQPQ PAPVHILLLS
60 70 80 90 100
LTLADLLLLL LLPFKIIEAA SNFRWYLPKV VCALTSFGFY SSIYCSTWLL
110 120 130 140 150
AGISIERYLG VAFPVQYKLS RRPLYGVIAA LVAWVMSFGH CTIVIIVQYL
160 170 180 190 200
NTTEQVRSGN EITCYENFTD NQLDVVLPVR LELCLVLFFI PMAVTIFCYW
210 220 230 240 250
RFVWIMLSQP LVGAQRRRRA VGLAVVTLLN FLVCFGPYNV SHLVGYHQRK
260 270 280 290 300
SPWWRSIAVV FSSLNASLDP LLFYFSSSVV RRAFGRGLQV LRNQGSSLLG
310 320 330
RRGKDTAEGT NEDRGVGQGE GMPSSDFTTE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 227 | T → M in AAH96201 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_011861 | 211 | L → H. Corresponds to variant dbSNP:rs409093Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF024690 Genomic DNA Translation: AAB86713.1 AC002511 Genomic DNA Translation: AAB67886.1 EU432114 Genomic DNA Translation: ABY87913.1 BC095535 mRNA Translation: AAH95535.1 BC096198 mRNA Translation: AAH96198.1 BC096199 mRNA Translation: AAH96199.1 BC096200 mRNA Translation: AAH96200.1 BC096201 mRNA Translation: AAH96201.1 |
CCDSi | CCDS12461.1 |
PIRi | JC5717 |
RefSeqi | NP_005297.1, NM_005306.2 XP_016882198.1, XM_017026709.1 XP_016882199.1, XM_017026710.1 XP_016882200.1, XM_017026711.1 |
Genome annotation databases
Ensembli | ENST00000246549; ENSP00000246549; ENSG00000126262 ENST00000599180; ENSP00000473159; ENSG00000126262 |
GeneIDi | 2867 |
KEGGi | hsa:2867 |
UCSCi | uc010eea.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF024690 Genomic DNA Translation: AAB86713.1 AC002511 Genomic DNA Translation: AAB67886.1 EU432114 Genomic DNA Translation: ABY87913.1 BC095535 mRNA Translation: AAH95535.1 BC096198 mRNA Translation: AAH96198.1 BC096199 mRNA Translation: AAH96199.1 BC096200 mRNA Translation: AAH96200.1 BC096201 mRNA Translation: AAH96201.1 |
CCDSi | CCDS12461.1 |
PIRi | JC5717 |
RefSeqi | NP_005297.1, NM_005306.2 XP_016882198.1, XM_017026709.1 XP_016882199.1, XM_017026710.1 XP_016882200.1, XM_017026711.1 |
3D structure databases
SMRi | O15552 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109125, 108 interactors |
IntActi | O15552, 106 interactors |
STRINGi | 9606.ENSP00000473159 |
Chemistry databases
BindingDBi | O15552 |
ChEMBLi | CHEMBL5493 |
DrugCentrali | O15552 |
GuidetoPHARMACOLOGYi | 226 |
SwissLipidsi | SLP:000001558 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | O15552, 2 sites |
iPTMneti | O15552 |
PhosphoSitePlusi | O15552 |
Polymorphism and mutation databases
BioMutai | FFAR2 |
Proteomic databases
PaxDbi | O15552 |
PeptideAtlasi | O15552 |
PRIDEi | O15552 |
ProteomicsDBi | 48754 |
Protocols and materials databases
Antibodypediai | 15916, 326 antibodies |
DNASUi | 2867 |
Genome annotation databases
Ensembli | ENST00000246549; ENSP00000246549; ENSG00000126262 ENST00000599180; ENSP00000473159; ENSG00000126262 |
GeneIDi | 2867 |
KEGGi | hsa:2867 |
UCSCi | uc010eea.4, human |
Organism-specific databases
CTDi | 2867 |
DisGeNETi | 2867 |
EuPathDBi | HostDB:ENSG00000126262.4 |
GeneCardsi | FFAR2 |
HGNCi | HGNC:4501, FFAR2 |
HPAi | ENSG00000126262, Tissue enhanced (blood, lymphoid tissue) |
MIMi | 603823, gene |
neXtProti | NX_O15552 |
OpenTargetsi | ENSG00000126262 |
PharmGKBi | PA28890 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQGM, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | O15552 |
OMAi | WVMSFGH |
OrthoDBi | 1129026at2759 |
PhylomeDBi | O15552 |
TreeFami | TF350010 |
Enzyme and pathway databases
PathwayCommonsi | O15552 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-444209, Free fatty acid receptors |
SIGNORi | O15552 |
Miscellaneous databases
BioGRID-ORCSi | 2867, 4 hits in 842 CRISPR screens |
GenomeRNAii | 2867 |
Pharosi | O15552, Tchem |
PROi | PR:O15552 |
RNActi | O15552, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000126262, Expressed in blood and 114 other tissues |
ExpressionAtlasi | O15552, baseline and differential |
Genevisiblei | O15552, HS |
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_HUMAN | |
Accessioni | O15552Primary (citable) accession number: O15552 Secondary accession number(s): B0M0J9 Q4VBL5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | January 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 158 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries