Free fatty acid receptor 4
Details
- Name
- Free fatty acid receptor 4
- Kind
- protein
- Synonyms
- G-protein coupled receptor 120
- G-protein coupled receptor 129
- G-protein coupled receptor GT01
- G-protein coupled receptor PGR4
- GPR120
- GPR129
- O3FAR1
- Omega-3 fatty acid receptor 1
- PGR4
- Gene Name
- FFAR4
- UniProtKB Entry
- Q5NUL3Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0058509|Free fatty acid receptor 4 MSPECARAAGDAPLRSLEQANRTRFPFFSDVKGDHRLVLAAVETTVLVLIFAVSLLGNVC ALVLVARRRRRGATACLVLNLFCADLLFISAIPLVLAVRWTEAWLLGPVACHLLFYVMTL SGSVTILTLAAVSLERMVCIVHLQRGVRGPGRRARAVLLALIWGYSAVAALPLCVFFRVV PQRLPGADQEISICTLIWPTIPGEISWDVSFVTLNFLVPGLVIVISYSKILQITKASRKR LTVSLAYSESHQIRVSQQDFRLFRTLFLLMVSFFIMWSPIIITILLILIQNFKQDLVIWP SLFFWVVAFTFANSALNPILYNMTLCRNEWKKIFCCFWFPEKGAILTDTSVKRNDLSIIS G
- Number of residues
- 361
- Molecular Weight
- 40493.84
- Theoretical pI
- 9.63
- GO Classification
- Functionsarrestin family protein binding / G protein-coupled receptor activity / peptide bindingProcessesadenylate cyclase-activating G protein-coupled receptor signaling pathway / brown fat cell differentiation / cellular response to hormone stimulus / G protein-coupled receptor signaling pathway / ghrelin secretion / inflammatory response / negative regulation of cytokine production / negative regulation of interleukin-1 beta production / negative regulation of somatostatin secretion / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of brown fat cell differentiation / positive regulation of cold-induced thermogenesis / positive regulation of cytosolic calcium ion concentration / positive regulation of glucagon secretion / positive regulation of osteoblast differentiation / regulation of glucose transmembrane transport / white fat cell differentiationComponentsciliary membrane / cilium / endosome membrane / lysosomal membrane
- General 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:22343897, PubMed:24742677, PubMed:24817122, PubMed:27852822). 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:22282525, PubMed:22343897, PubMed:24742677, PubMed:27852822). 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 pro-inflammatory cytokine release (PubMed:23809162). Mediates LCFAs anti-apoptotic effects (By similarity)
- Specific Function
- arrestin family protein binding
- Pfam Domain Function
- 7tm_1 (PF00001)
- Signal Regions
- Not Available
- Transmembrane Regions
- 46-66 78-98 113-133 157-177 205-225 269-289 296-316
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0020685|Free fatty acid receptor 4 (FFAR4) ATGTCCCCTGAATGCGCGCGGGCAGCGGGCGACGCGCCCTTGCGCAGCCTGGAGCAAGCC AACCGCACCCGCTTTCCCTTCTTCTCCGACGTCAAGGGCGACCACCGGCTGGTGCTGGCC GCGGTGGAGACAACCGTGCTGGTGCTCATCTTTGCAGTGTCGCTGCTGGGCAACGTGTGC GCCCTGGTGCTGGTGGCGCGCCGACGACGCCGCGGCGCGACTGCCTGCCTGGTACTCAAC CTCTTCTGCGCGGACCTGCTCTTCATCAGCGCTATCCCTCTGGTGCTGGCCGTGCGCTGG ACTGAGGCCTGGCTGCTGGGCCCCGTTGCCTGCCACCTGCTCTTCTACGTGATGACCCTG AGCGGCAGCGTCACCATCCTCACGCTGGCCGCGGTCAGCCTGGAGCGCATGGTGTGCATC GTGCACCTGCAGCGCGGCGTGCGGGGTCCTGGGCGGCGGGCGCGGGCAGTGCTGCTGGCG CTCATCTGGGGCTATTCGGCGGTCGCCGCTCTGCCTCTCTGCGTCTTCTTCCGAGTCGTC CCGCAACGGCTCCCCGGCGCCGACCAGGAAATTTCGATTTGCACACTGATTTGGCCCACC ATTCCTGGAGAGATCTCGTGGGATGTCTCTTTTGTTACTTTGAACTTCTTGGTGCCAGGA CTGGTCATTGTGATCAGTTACTCCAAAATTTTACAGATCACAAAGGCATCAAGGAAGAGG CTCACGGTAAGCCTGGCCTACTCGGAGAGCCACCAGATCCGCGTGTCCCAGCAGGACTTC CGGCTCTTCCGCACCCTCTTCCTCCTCATGGTCTCCTTCTTCATCATGTGGAGCCCCATC ATCATCACCATCCTCCTCATCCTGATCCAGAACTTCAAGCAAGACCTGGTCATCTGGCCG TCCCTCTTCTTCTGGGTGGTGGCCTTCACATTTGCTAATTCAGCCCTAAACCCCATCCTC TACAACATGACACTGTGCAGGAATGAGTGGAAGAAAATTTTTTGCTGCTTCTGGTTCCCA GAAAAGGGAGCCATTTTAACAGACACATCTGTCAAAAGAAATGACTTGTCGATTATTTCT GGCTAA
- Chromosome Location
- 10
- Locus
- 10q23.33
- External Identifiers
Resource Link UniProtKB ID Q5NUL3 UniProtKB Entry Name FFAR4_HUMAN GenBank Gene ID AY288417 GeneCard ID FFAR4 GenAtlas ID GPR120 HGNC ID HGNC:19061 PDB ID(s) 8G59, 8H4I, 8H4K, 8H4L, 8ID3, 8ID4, 8ID6, 8ID8, 8ID9, 8IYS, 8T3O, 8T3Q KEGG ID hsa:338557 IUPHAR/Guide To Pharmacology ID 127 NCBI Gene ID 338557 - General References
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- Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G: Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med. 2005 Jan;11(1):90-4. Epub 2004 Dec 26. [Article]
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- Burns RN, Moniri NH: Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem Biophys Res Commun. 2010 Jun 11;396(4):1030-5. doi: 10.1016/j.bbrc.2010.05.057. Epub 2010 May 13. [Article]
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