General Information of the Protein
Protein ID
PT03121
Protein Name
Free fatty acid receptor 4
Secondarily
Protein Name
G-protein coupled receptor 120
G-protein coupled receptor GT01
Omega-3 fatty acid receptor 1
Gene Name
FFAR4
Secondarily
Gene Name
Gpr120
O3far1
Sequence
MSPECAQTTGPGPSHTLDQVNRTHFPFFSDVKGDHRLVLSVVETTVLGLIFVVSLLGNVCALVLVARRRRRGATASLVLNLFCADLLFTSAIPLVLVVRWTEAWLLGPVVCHLLFYVMTMSGSVTILTLAAVSLERMVCIVRLRRGLSGPGRRTQAALLAFIWGYSALAALPLCILFRVVPQRLPGGDQEIPICTLDWPNRIGEISWDVFFVTLNFLVPGLVIVISYSKILQITKASRKRLTLSLAYSESHQIRVSQQDYRLFRTLFLLMVSFFIMWSPIIITILLILIQNFRQDLVIWPSLFFWVVAFTFANSALNPILYNMSLFRNEWRKIFCCFFFPEKGAIFTDTSVRRNDLSVISS
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Organism
Mus musculus, Mouse
Protein Classification
Membrane receptor
>
Family A G protein-coupled receptor
>
Small molecule receptor (family A GPCR)
>
Lipid-like ligand receptor (family A GPCR)
>
Free fatty acid receptor
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:27852822, PubMed:26873857). 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:26873857). 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:27852822, PubMed:26873857). In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation (PubMed:17250804, PubMed:22343897, PubMed:27853148, PubMed:29343498, PubMed:31761534). 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 (PubMed:31761534). Induces differentiation of brown and beige adipocytes probably via autocrine and endocrine functions of FGF21 hormone (PubMed:27853148, PubMed:29343498). Contributes to the thermogenic activation of brown adipose tissue and the browning of white adipose tissue (PubMed:27853148, PubMed:29343498). Activates brown adipocytes by initiating intracellular calcium signaling leading to mitochondrial depolarization and fission, and overall increased mitochondrial respiration (PubMed:29343498). Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass (PubMed:29343498). Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins (PubMed:26365922). In response to dietary fats regulates hormone secretion and appetite (PubMed:15619630, PubMed:25535828, PubMed:24742677, PubMed:24663807, PubMed:24222669). 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 (PubMed:15619630, PubMed:25535828, PubMed:24742677). Negatively regulates glucose-induced SST secretion in pancreatic delta cells (PubMed:24663807). Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling hormone (PubMed:24222669). In taste buds, contributes to sensing of dietary fatty acids by the gustatory system (PubMed:20573884). During the inflammatory response, promotes anti-inflammatory M2 macrophage differentiation in adipose tissue (PubMed:20813258). Mediates the anti-inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 inflammasome activation (By similarity). 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 (PubMed:20813258). Further inhibits the activation step when ARRB2 directly associates with NLRP3, leading to inhibition of pro-inflammatory cytokine release (By similarity). Mediates LCFAs anti-apoptotic effects (PubMed:15774482).
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Uniprot ID
Q7TMA4
Subcellular Location
Cell membrane
Endosome membrane
Lysosome membrane
Cell projection
Cilium membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000026 , CHO-K1
Compound ID Compound Name Compound Formula
CP0219930
3-[(2R)-6-[3-fluoro-4-methoxy-6-(3-methoxycyclobutyl)oxypyridin-2-yl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid
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C23H26FNO6
 1
1
EC50 = 5.6 nM
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CP0048202
3-[(2R)-6-[3,4-difluoro-6-(3-methoxycyclobutyl)oxypyridin-2-yl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid
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C22H23F2NO5
 1
1
EC50 = 6.4 nM
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CP0048253
4-[2,6-difluoro-4-[2-fluoro-5-(trifluoromethoxy)phenyl]phenoxy]butanoic acid
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C17H12F6O4
 1
1
EC50 = 7 nM
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CP0048254
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]phenoxy]butanoic acid
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C17H14ClF3O4
 1
1
EC50 = 9 nM
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CP0388566
3-[5-[2-chloro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid
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C18H12ClF3O4
 1
1
EC50 = 12 nM
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CP0085978
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-2,6-dimethylphenoxy]butanoic acid
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C19H18ClF3O4
 1
1
EC50 = 16 nM
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CP0220860
3-[5-[5-(cyclopropanecarbonyl)-2-fluorophenyl]-1-benzofuran-2-yl]propanoic acid
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C21H17FO4
 1
1
EC50 = 22 nM
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CP0153988
4-[4-[2-fluoro-5-(3-fluorophenoxy)phenyl]phenoxy]butanoic acid
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C22H18F2O4
 1
1
EC50 = 27 nM
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CP0048251
3-[5-(3-cyclobutyloxy-5-methylphenyl)-1-benzofuran-2-yl]propanoic acid
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C22H22O4
 1
1
EC50 = 28 nM
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CP0191029
4-[4-(2-fluoro-5-phenoxyphenyl)phenoxy]butanoic acid
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C22H19FO4
 1
1
EC50 = 29 nM
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CP0302776
4-[4-(5-cyclopropyloxy-2-fluorophenyl)phenoxy]butanoic acid
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C19H19FO4
 1
1
EC50 = 32 nM
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CP0346517
4-[4-(2-chloro-5-ethoxyphenyl)phenoxy]butanoic acid
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C18H19ClO4
 1
1
EC50 = 32 nM
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CP0172418
2-[3-[2-chloro-5-(trifluoromethoxy)phenyl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C19H23ClF3NO3
 1
1
EC50 = 33 nM
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CP0048249
4-[4-(2-chloro-5-pyridin-3-yloxyphenyl)phenoxy]butanoic acid
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C21H18ClNO4
 1
1
EC50 = 34 nM
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CP0504415
4-[4-[2-chloro-5-(3-fluorophenoxy)phenyl]phenoxy]butanoic acid
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C22H18ClFO4
 1
1
EC50 = 34 nM
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CP0220861
3-[5-(3-cyclobutyloxyphenyl)-1-benzofuran-2-yl]propanoic acid
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C21H20O4
 1
1
EC50 = 35 nM
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CP0562935
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-3-fluorophenoxy]butanoic acid
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C17H13ClF4O4
 1
1
EC50 = 36 nM
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CP0048255
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid
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C18H12F4O4
 1
1
EC50 = 43 nM
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CP0464379
2-[3-[3-cyano-5-(trifluoromethylsulfanyl)phenyl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C20H23F3N2O2S
 1
1
EC50 = 44 nM
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CP0191030
4-[4-[2-fluoro-5-(trifluoromethoxy)phenyl]-2,6-dimethylphenoxy]butanoic acid
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C19H18F4O4
 1
1
EC50 = 47 nM
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CP0466653
2-[3-[2-fluoro-5-(trifluoromethoxy)phenyl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C19H23F4NO3
 1
1
EC50 = 49 nM
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CP0396176
2-[3-(3,5-dichlorophenyl)-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C18H23Cl2NO2
 1
1
EC50 = 51 nM
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CP0048252
3-[5-(3-chloro-5-cyclobutyloxyphenyl)-1-benzofuran-2-yl]propanoic acid
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C21H19ClO4
 1
1
EC50 = 64 nM
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CP0294302
4-[4-[3-(4-methylphenoxy)phenyl]phenoxy]butanoic acid
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C23H22O4
 1
1
EC50 = 66 nM
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CP0464376
2-[3-[2-cyano-5-(trifluoromethoxy)phenyl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C20H23F3N2O3
 1
1
EC50 = 66 nM
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CP0071468
4-[4-(3-phenoxyphenyl)phenoxy]butanoic acid
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C22H20O4
 1
1
EC50 = 67 nM
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CP0370088
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]-2-methylpropanoic acid
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C19H14F4O4
 1
1
EC50 = 70 nM
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CP0534630
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]butanoic acid
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C19H14F4O4
 1
1
EC50 = 74 nM
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CP0153986
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-3-methylphenoxy]butanoic acid
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C18H16ClF3O4
 1
1
EC50 = 78 nM
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CP0370086
4-[4-[2-fluoro-5-(trifluoromethoxy)phenyl]-2-methylphenoxy]butanoic acid
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C18H16F4O4
 1
1
EC50 = 79 nM
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CP0190800
4-[4-[2-chloro-5-(1,3-thiazol-3-ium-3-yl)phenyl]phenoxy]butanoic acid
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C19H17ClNO3S+
 1
1
EC50 = 81 nM
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CP0346511
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-2-methylphenoxy]butanoic acid
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C18H16ClF3O4
 1
1
EC50 = 131 nM
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CP0190955
4-[4-(5-ethoxy-2-fluorophenyl)phenoxy]butanoic acid
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C18H19FO4
 1
1
EC50 = 140 nM
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CP0461738
2-[3-(3-chloro-2,5-difluorophenyl)-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C18H22ClF2NO2
 1
1
EC50 = 190 nM
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CP0089979
4-[4-[3-(3-methoxyphenoxy)phenyl]phenoxy]butanoic acid
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C23H22O5
 1
1
EC50 = 264 nM
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CP0508078
5-[2-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]ethyl]-2H-tetrazole
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C18H12F4N4O2
 1
1
EC50 = 316 nM
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CP0370087
3-[5-[3-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid
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C18H13F3O4
 1
1
EC50 = 326 nM
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CP0398697
4-[4-(2-phenoxyphenyl)phenoxy]butanoic acid
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C22H20O4
 1
1
EC50 = 418 nM
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CP0534629
4-[4-[2-fluoro-5-(trifluoromethoxy)phenyl]phenoxy]butanoic acid
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C17H14F4O4
 1
1
EC50 = 432 nM
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CP0408977
4-[4-(1,2-benzoxazol-3-yl)-2,3-dichlorophenoxy]butanoic acid
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C17H13Cl2NO4
 1
1
EC50 = 487 nM
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CP0503952
2-[3-(2-chloro-5-methoxyphenyl)-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C19H26ClNO3
 1
1
EC50 = 570 nM
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CP0396175
2-[3-[2-fluoro-5-(trifluoromethyl)phenyl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C19H23F4NO2
 1
1
EC50 = 590 nM
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CP0516513
2-[3-(5-chloro-2,2-dimethyl-3H-1-benzofuran-7-yl)-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C22H30ClNO3
 1
1
EC50 = 670 nM
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CP0500271
2-[3-[4-(trifluoromethyl)pyridin-2-yl]-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C18H23F3N2O2
 1
1
EC50 = 1300 nM
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CP0089978
4-[4-[2-(trifluoromethoxy)phenyl]phenoxy]butanoic acid
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C17H15F3O4
 1
1
EC50 = 1872 nM
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CP0455040
4-[4-[2-(trifluoromethyl)phenyl]phenoxy]butanoic acid
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C17H15F3O3
 1
1
EC50 = 2189 nM
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CP0469180
2-[3-(2-chlorophenyl)-3-azaspiro[5.5]undecan-9-yl]acetic acid
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C18H24ClNO2
 1
1
EC50 > 10000 nM
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CP0048250
4-[4-(3-phenylmethoxyphenyl)phenoxy]butanoic acid
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C23H22O4
 1
1
EC50 > 9950 nM
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CP0541540
5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxylic acid
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C16H8F4O4
 1
1
EC50 > 9950 nM
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Biochemical Assays
Compound ID Compound Name Compound Formula
CP0085978
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-2,6-dimethylphenoxy]butanoic acid
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C19H18ClF3O4
 2
1 EC50 = 16 nM
2 EC50 = 35 nM
CP0048255
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid
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C18H12F4O4
 2
1 EC50 = 21 nM
2 EC50 = 43 nM
Similar Protein(s) and Bioactivity Statistics
90% Identity
Protein ID Protein Name Protein Organism
PT05503 Free fatty acid receptor 4 Rattus norvegicus, Rat
50% Identity
Protein ID Protein Name Protein Organism
PT04427 Free fatty acid receptor 4 Homo sapiens, Human