| Identification |
|---|
| HMDB Protein ID
| CDBP05648 |
| Secondary Accession Numbers
| Not Available |
| Name
| Free fatty acid receptor 4 |
| Description
| Not Available |
| Synonyms
|
Not Available
|
| Gene Name
| FFAR4 |
| Protein Type
| Receptor |
| Biological Properties |
|---|
| General Function
| taste receptor activity |
| Specific Function
| G-protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation. Signals via G-protein and beta-arrestin pathways (PubMed:22282525, PubMed:24742677, PubMed:27852822, PubMed:24817122, PubMed:22343897). LCFAs sensing initiates activation of phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second messenger pathways such as intracellular calcium mobilization, modulation of cyclic adenosine monophosphate (cAMP) production, and mitogen-activated protein kinases (MAPKs) (PubMed:27852822, PubMed:22343897, PubMed:22282525, PubMed:24742677). After LCFAs binding, associates with beta-arrestin ARRB2 that acts as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:24817122). In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation (By similarity). Acts as a receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular preadipocytes, initiating an adipogenic program via cAMP and CTCF-dependent chromatin remodeling that ultimately results in transcriptional activation of adipogenic genes and cell cycle entry (By similarity). Induces differentiation of brown adipocytes probably via autocrine and endocrine functions of FGF21 hormone (By similarity). Activates brown adipocytes by initiating intracellular calcium signaling that leads to mitochondrial depolarization and fission, and overall increased mitochondrial respiration (By similarity). Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass (By similarity). Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins (By similarity). In response to dietary fats regulates hormone secretion and appetite (By similarity). Stimulates GIP and GLP1 secretion from enteroendocrine cells as well as GCG secretion in pancreatic alpha cells, thereby playing a role in the regulation of blood glucose levels (By similarity). Negatively regulates glucose-induced SST secretion in pancreatic delta cells (By similarity). Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling hormone (By similarity). In taste buds, contributes to sensing of dietary fatty acids by the gustatory system (By similarity). During the inflammatory response, promotes anti-inflammatory M2 macrophage differentiation in adipose tissue (By similarity). Mediates the anti-inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 inflammasome activation (PubMed:23809162). In this pathway, interacts with adapter protein ARRB2 and inhibits the priming step triggered by Toll-like receptors (TLRs) at the level of TAK1 and TAB1 (By similarity). Further inhibits the activation step when ARRB2 directly associates with NLRP3, leading to inhibition of proinflammatory cytokine release (PubMed:23809162). Mediates LCFAs anti-apoptotic effects (By similarity).Receptor for LCFAs decoupled from G-protein signaling. May signal through beta-arrestin pathway. After LCFAs binding, associates with beta-arrestin ARRB2 that may act as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. |
| GO Classification
|
| Biological Process |
| ghrelin secretion |
| white fat cell differentiation |
| hormone secretion |
| phospholipase C-activating G-protein coupled receptor signaling pathway |
| negative regulation of cytokine secretion |
| positive regulation of ERK1 and ERK2 cascade |
| negative regulation of somatostatin secretion |
| positive regulation of cAMP-mediated signaling |
| positive regulation of glucagon secretion |
| positive regulation of osteoblast differentiation |
| positive regulation of brown fat cell differentiation |
| elevation of cytosolic calcium ion concentration |
| regulation of glucose transport |
| negative regulation of apoptotic process |
| negative regulation of inflammatory response |
| G-protein coupled receptor signaling pathway |
| negative regulation of interleukin-1 beta production |
| positive regulation of cold-induced thermogenesis |
| inflammatory response |
| brown fat cell differentiation |
| Cellular Component |
| cilium |
| plasma membrane |
| endocytic vesicle |
| endosome membrane |
| lysosomal membrane |
| integral to plasma membrane |
| cell |
| ciliary membrane |
| Molecular Function |
| fatty acid binding |
| G protein-coupled receptor activity |
| taste receptor activity |
| arrestin family protein binding |
|
| Cellular Location
|
- Cell membrane
- Endosome membrane
- Lysosome membrane
- Cell projection
- cilium membrane
|
| Pathways
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| 10 |
| Locus
| 10q23.33 |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| 361 |
| Molecular Weight
| 40493.84 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
- ["46-66", "78-98", "113-133", "157-177", "205-225", "269-289", "296-316"]
|
| Protein Sequence
|
>Free fatty acid receptor 4
MSPECARAAGDAPLRSLEQANRTRFPFFSDVKGDHRLVLAAVETTVLVLIFAVSLLGNVC
ALVLVARRRRRGATACLVLNLFCADLLFISAIPLVLAVRWTEAWLLGPVACHLLFYVMTL
SGSVTILTLAAVSLERMVCIVHLQRGVRGPGRRARAVLLALIWGYSAVAALPLCVFFRVV
PQRLPGADQEISICTLIWPTIPGEISWDVSFVTLNFLVPGLVIVISYSKILQITKASRKR
LTVSLAYSESHQIRVSQQDFRLFRTLFLLMVSFFIMWSPIIITILLILIQNFKQDLVIWP
SLFFWVVAFTFANSALNPILYNMTLCRNEWKKIFCCFWFPEKGAILTDTSVKRNDLSIIS
G
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q5NUL3 |
| UniProtKB/Swiss-Prot Entry Name
| FFAR4_HUMAN |
| PDB IDs
|
Not Available |
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| HGNC:19061 |
| References |
|---|
| General References
| Not Available |