UniProtKB - O14843 (FFAR3_HUMAN)
Protein
Free fatty acid receptor 3
Gene
FFAR3
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. 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 (PubMed:12711604). 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. 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. 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. 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. Finally, may also play a role in glucose homeostasis. 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. Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably propionate, butyrate and pentanoate while acetate is a poor activator (PubMed:12496283, PubMed:12711604).4 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: UniProtKB
- cellular response to fatty acid 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 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 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
PathwayCommonsi | O14843 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-444209, Free fatty acid receptors |
SIGNORi | O14843 |
Chemistry databases
SwissLipidsi | SLP:000001557 |
Names & Taxonomyi
Protein namesi | Recommended name: Free fatty acid receptor 3Alternative name(s): G-protein coupled receptor 41 |
Gene namesi | Name:FFAR3 Synonyms:GPR41 |
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:ENSG00000185897.6 |
HGNCi | HGNC:4499, FFAR3 |
MIMi | 603821, gene |
neXtProti | NX_O14843 |
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
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 19 | ExtracellularSequence analysisAdd BLAST | 19 | |
Transmembranei | 20 – 40 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 41 – 47 | Cytoplasmic | 7 | |
Transmembranei | 48 – 68 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 69 – 88 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 89 – 111 | Helical; Name=3Sequence analysisAdd BLAST | 23 | |
Topological domaini | 112 – 132 | CytoplasmicSequence analysisAdd BLAST | 21 | |
Transmembranei | 133 – 153 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 154 – 178 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 179 – 199 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 200 – 222 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 223 – 243 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 244 – 258 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 259 – 279 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 280 – 346 | CytoplasmicSequence analysisAdd BLAST | 67 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 146 | H → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 158 | D → N: Gain of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 185 | R → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 245 | H → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 | |
Mutagenesisi | 258 | R → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2865 |
OpenTargetsi | ENSG00000185897 |
PharmGKBi | PA28888 |
Miscellaneous databases
Pharosi | O14843, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5201 |
GuidetoPHARMACOLOGYi | 227 |
Polymorphism and mutation databases
BioMutai | FFAR3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069569 | 1 – 346 | Free fatty acid receptor 3Add BLAST | 346 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 88 ↔ 169 | PROSITE-ProRule annotation | ||
Glycosylationi | 166 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | O14843 |
PeptideAtlasi | O14843 |
PRIDEi | O14843 |
ProteomicsDBi | 48274 |
PTM databases
GlyGeni | O14843, 1 site |
Expressioni
Tissue specificityi
Highest level in adipose tissue, and lower expression across all tissues tested. Expressed in sympathetic ganglia.2 Publications
Gene expression databases
Bgeei | ENSG00000185897, Expressed in blood and 79 other tissues |
ExpressionAtlasi | O14843, baseline and differential |
Genevisiblei | O14843, HS |
Organism-specific databases
HPAi | ENSG00000185897, Tissue enhanced (adipose tissue, blood, lymphoid tissue) |
Interactioni
Binary interactionsi
Hide detailsO14843
Protein-protein interaction databases
BioGRIDi | 109123, 14 interactors |
IntActi | O14843, 13 interactors |
STRINGi | 9606.ENSP00000328230 |
Chemistry databases
BindingDBi | O14843 |
Miscellaneous databases
RNActi | O14843, 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 | O14843 |
OMAi | AYPLWYK |
OrthoDBi | 1129026at2759 |
PhylomeDBi | O14843 |
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.
O14843-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDTGPDQSYF SGNHWFVFSV YLLTFLVGLP LNLLALVVFV GKLQRRPVAV
60 70 80 90 100
DVLLLNLTAS DLLLLLFLPF RMVEAANGMH WPLPFILCPL SGFIFFTTIY
110 120 130 140 150
LTALFLAAVS IERFLSVAHP LWYKTRPRLG QAGLVSVACW LLASAHCSVV
160 170 180 190 200
YVIEFSGDIS HSQGTNGTCY LEFRKDQLAI LLPVRLEMAV VLFVVPLIIT
210 220 230 240 250
SYCYSRLVWI LGRGGSHRRQ RRVAGLLAAT LLNFLVCFGP YNVSHVVGYI
260 270 280 290 300
CGESPAWRIY VTLLSTLNSC VDPFVYYFSS SGFQADFHEL LRRLCGLWGQ
310 320 330 340
WQQESSMELK EQKGGEEQRA DRPAERKTSE HSQGCGTGGQ VACAES
Polymorphismi
The 6 amino acid differences at positions 44, 45, 174, 227, 256 and 346 between GPR42 and FFAR3, are polymorphic in the human population. The frequency of the probable inactive allele of FFAR3, with a Trp at position 174 was estimated to 1%.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_062854 | 44 | Q → R1 PublicationCorresponds to variant dbSNP:rs382771Ensembl. | 1 | |
Natural variantiVAR_062855 | 45 | R → C1 PublicationCorresponds to variant dbSNP:rs1359000742Ensembl. | 1 | |
Natural variantiVAR_062856 | 174 | R → W Abolishes activation by propionate. 2 PublicationsCorresponds to variant dbSNP:rs1415955990Ensembl. | 1 | |
Natural variantiVAR_062857 | 227 | L → V1 PublicationCorresponds to variant dbSNP:rs1395869674Ensembl. | 1 | |
Natural variantiVAR_062858 | 256 | A → V1 PublicationCorresponds to variant dbSNP:rs1170582382Ensembl. | 1 | |
Natural variantiVAR_062962 | 346 | S → N1 PublicationCorresponds to variant dbSNP:rs201080710Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF024688 Genomic DNA Translation: AAB86711.1 U62631 Genomic DNA No translation available. BC035657 mRNA Translation: AAH35657.1 BC113695 mRNA Translation: AAI13696.1 BC148269 mRNA Translation: AAI48270.1 |
CCDSi | CCDS12459.1 |
PIRi | JC5715 |
RefSeqi | NP_005295.1, NM_005304.4 |
Genome annotation databases
Ensembli | ENST00000327809; ENSP00000328230; ENSG00000185897 ENST00000594310; ENSP00000469522; ENSG00000185897 |
GeneIDi | 2865 |
KEGGi | hsa:2865 |
UCSCi | uc002nzd.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF024688 Genomic DNA Translation: AAB86711.1 U62631 Genomic DNA No translation available. BC035657 mRNA Translation: AAH35657.1 BC113695 mRNA Translation: AAI13696.1 BC148269 mRNA Translation: AAI48270.1 |
CCDSi | CCDS12459.1 |
PIRi | JC5715 |
RefSeqi | NP_005295.1, NM_005304.4 |
3D structure databases
SMRi | O14843 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109123, 14 interactors |
IntActi | O14843, 13 interactors |
STRINGi | 9606.ENSP00000328230 |
Chemistry databases
BindingDBi | O14843 |
ChEMBLi | CHEMBL5201 |
GuidetoPHARMACOLOGYi | 227 |
SwissLipidsi | SLP:000001557 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | O14843, 1 site |
Polymorphism and mutation databases
BioMutai | FFAR3 |
Proteomic databases
PaxDbi | O14843 |
PeptideAtlasi | O14843 |
PRIDEi | O14843 |
ProteomicsDBi | 48274 |
Protocols and materials databases
Antibodypediai | 55509, 167 antibodies |
DNASUi | 2865 |
Genome annotation databases
Ensembli | ENST00000327809; ENSP00000328230; ENSG00000185897 ENST00000594310; ENSP00000469522; ENSG00000185897 |
GeneIDi | 2865 |
KEGGi | hsa:2865 |
UCSCi | uc002nzd.4, human |
Organism-specific databases
CTDi | 2865 |
DisGeNETi | 2865 |
EuPathDBi | HostDB:ENSG00000185897.6 |
GeneCardsi | FFAR3 |
HGNCi | HGNC:4499, FFAR3 |
HPAi | ENSG00000185897, Tissue enhanced (adipose tissue, blood, lymphoid tissue) |
MIMi | 603821, gene |
neXtProti | NX_O14843 |
OpenTargetsi | ENSG00000185897 |
PharmGKBi | PA28888 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQGM, Eukaryota |
GeneTreei | ENSGT00990000203527 |
HOGENOMi | CLU_009579_8_4_1 |
InParanoidi | O14843 |
OMAi | AYPLWYK |
OrthoDBi | 1129026at2759 |
PhylomeDBi | O14843 |
TreeFami | TF350010 |
Enzyme and pathway databases
PathwayCommonsi | O14843 |
Reactomei | R-HSA-416476, G alpha (q) signalling events R-HSA-444209, Free fatty acid receptors |
SIGNORi | O14843 |
Miscellaneous databases
BioGRID-ORCSi | 2865, 6 hits in 815 CRISPR screens |
GeneWikii | Free_fatty_acid_receptor_3 |
GenomeRNAii | 2865 |
Pharosi | O14843, Tchem |
PROi | PR:O14843 |
RNActi | O14843, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000185897, Expressed in blood and 79 other tissues |
ExpressionAtlasi | O14843, baseline and differential |
Genevisiblei | O14843, 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 | FFAR3_HUMAN | |
Accessioni | O14843Primary (citable) accession number: O14843 Secondary accession number(s): B2RWM8, Q14CM7 | |
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