General Information of the Protein
Protein ID
PT04427
Protein Name
Free fatty acid receptor 4
Secondarily
Protein Name
G-protein coupled receptor 120
G-protein coupled receptor 129
G-protein coupled receptor GT01
G-protein coupled receptor PGR4
Omega-3 fatty acid receptor 1
Gene Name
FFAR4
Secondarily
Gene Name
GPR120
GPR129
O3FAR1
PGR4
Sequence
MSPECARAAGDAPLRSLEQANRTRFPFFSDVKGDHRLVLAAVETTVLVLIFAVSLLGNVCALVLVARRRRRGATACLVLNLFCADLLFISAIPLVLAVRWTEAWLLGPVACHLLFYVMTLSGSVTILTLAAVSLERMVCIVHLQRGVRGPGRRARAVLLALIWGYSAVAALPLCVFFRVVPQRLPGADQEISICTLIWPTIPGEISWDVSFVTLNFLVPGLVIVISYSKILQITKASRKRLTVSLAYSESHQIRVSQQDFRLFRTLFLLMVSFFIMWSPIIITILLILIQNFKQDLVIWPSLFFWVVAFTFANSALNPILYNMTLCRNEWKKIFCCFWFPEKGAILTDTSVKRNDLSIISG
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Organism
Homo sapiens, Human
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: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 pro-inflammatory cytokine release (PubMed:23809162). Mediates LCFAs anti-apoptotic effects (By similarity).
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Uniprot ID
Primary ID:
Q5NUL3

Secondarily ID:
Q495H1
Q5VY25
Q5VY26
Q7Z605
Q86SM7
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HGNC ID
HGNC:19061
Subcellular Location
Cell membrane
Endosome membrane
Lysosome 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: CL000011 , CHO
Compound ID Compound Name Compound Formula
CP0860299
3-(4-((4-Fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic-2,2-d2 acid
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C23H21FO3
 1
1
EC50 = 63.1 nM
   TI
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CP0438829
4-[4-(2,3-difluoro-5-methoxyphenyl)-2,6-difluorophenoxy]butanoic acid
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C17H14F4O4
 1
1
EC50 = 69 nM
   TI
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   TS
CP0145583
3-[4-[[5-fluoro-2-(4-methylphenyl)phenyl]methoxy]phenyl]propanoic acid
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C23H21FO3
 1
1
EC50 = 75.3 nM
   TI
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CP0478430
4-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]butanoic acid
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C21H20F4O5
 1
1
EC50 = 93 nM
   TI
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CP0960219
3-(4-((4-Fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic-2,2-d2 acid
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C22H19FO3
 1
1
EC50 = 126.8 nM
   TI
   LI
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CP0435993
5-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]pentanoic acid
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C22H22F4O5
 1
1
EC50 = 186 nM
   TI
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CP0902466
3-(4-((4'-Methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic-2,2-d2 acid
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C23H22O3
 1
1
EC50 = 195.6 nM
   TI
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CP0412528
CHEMBL4250664
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C22H22F2O7
 1
1
EC50 = 220 nM
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CP0427751
4-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenyl]sulfanylbutanoic acid
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C21H20F4O4S
 1
1
EC50 = 347 nM
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CP0930429
3-(4-([1,1'-Biphenyl]-2-ylmethoxy)phenyl)propanoic-2,2-d2 acid
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C22H20O3
 1
1
EC50 = 396.2 nM
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CP0487116
3-[(2R)-6-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid
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C23H24F2O5
 1
1
EC50 = 463 nM
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CP0456326
6-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]hexanoic acid
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C23H24F4O5
 1
1
EC50 = 638 nM
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CP0427750
CHEMBL4239630
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C23H26F2O5
 1
1
EC50 = 874 nM
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CP0487158
4-[2,6-difluoro-4-[2-(propan-2-ylamino)phenyl]phenoxy]butanoic acid
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C19H21F2NO3
 1
1
EC50 = 1470 nM
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CP0487115
4-[2,6-difluoro-4-[5-(3-methoxycyclobutyl)oxy-2-nitrophenyl]phenoxy]butanoic acid
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C21H21F2NO7
 1
1
EC50 = 1478 nM
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CP0555832
4-[4-[2,3-difluoro-5-(oxan-4-yloxy)phenyl]-2,6-difluorophenoxy]butanoic acid
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C21H20F4O5
 1
1
EC50 = 2780 nM
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CP0478431
4-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]-2,2-dimethylbutanoic acid
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C23H24F4O5
 1
1
EC50 = 5039 nM
   TI
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CP0862686
[(3S)-6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]-biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic Acid Hemihydrate
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C29H34O8S
 1
1
EC50 > 10000 nM
   TI
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CP0078179
3-[4-[[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methoxy]phenyl]propanoic acid
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C18H15ClN2O4
 1
1
EC50 > 10000 nM
   TI
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CP0078180
3-[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]propanoic acid
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C20H19NO4
 1
1
EC50 > 10000 nM
   TI
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CP0141574
3-[4-[[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methoxy]phenyl]propanoic acid
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C19H18N2O4
 1
1
EC50 > 10000 nM
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CP0054882
3-[5-[[3-(4-fluorophenyl)phenyl]carbamoyl]-1,3,4-thiadiazol-2-yl]propanoic acid
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C18H14FN3O3S
 1
1
EC50 > 10000 nM
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CP0065854
3-[5-[[3-(3-methylphenyl)phenyl]carbamoyl]-1,3,4-thiadiazol-2-yl]propanoic acid
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C19H17N3O3S
 1
1
EC50 > 10000 nM
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CP0191122
3-[4-[[5-[(2-fluorophenyl)carbamoyl]-1,3,4-thiadiazol-2-yl]methoxy]phenyl]propanoic acid
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C19H16FN3O4S
 1
1
EC50 > 10000 nM
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CP0452086
3-[4-[[5-[(3,4-difluorophenyl)carbamoyl]-1,3,4-thiadiazol-2-yl]methoxy]phenyl]propanoic acid
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C19H15F2N3O4S
 1
1
EC50 > 10000 nM
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CP0388929
3-[4-[[4-[(4-benzyl-1-oxa-9-azaspiro[5.5]undecan-9-yl)methyl]phenyl]methoxy]phenyl]propanoic acid;hydrochloride
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C33H40ClNO4
 1
1
EC50 > 10000 nM
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CP0400943
3-[4-[[4-[[4-[(4-methoxyphenyl)methyl]-1-oxa-9-azaspiro[5.5]undecan-9-yl]methyl]phenyl]methoxy]phenyl]propanoic acid;hydrochloride
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C34H42ClNO5
 1
1
EC50 > 10000 nM
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CP0455532
3-[4-[[4-[[4-[(4-fluorophenyl)methyl]-1-oxa-9-azaspiro[5.5]undecan-9-yl]methyl]phenyl]methoxy]phenyl]propanoic acid;hydrochloride
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C33H39ClFNO4
 1
1
EC50 > 10000 nM
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CP0456185
3-[4-[[4-[[4-[(4-methylphenyl)methyl]-1-oxa-9-azaspiro[5.5]undecan-9-yl]methyl]phenyl]methoxy]phenyl]propanoic acid;hydrochloride
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C34H42ClNO4
 1
1
EC50 > 10000 nM
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CP0476696
3-[4-[[4-[[4-[2-(6-methylpyridin-2-yl)oxyethyl]-1-oxa-9-azaspiro[5.5]undecan-9-yl]methyl]phenyl]methoxy]phenyl]propanoic acid;dihydrochloride
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C34H44Cl2N2O5
 1
1
EC50 > 10000 nM
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CP0393671
(3R)-3-[5-[[3-(2,6-dimethylphenyl)phenyl]methoxy]thiophen-2-yl]-3-ethoxypropanoic acid
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C24H26O4S
 1
1
EC50 > 10000 nM
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CP0408053
3-[5-[[3-(2,6-dimethylphenyl)phenyl]methoxy]thiophen-2-yl]propanoic acid
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C22H22O3S
 1
1
EC50 > 10000 nM
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CP0420403
(3R)-3-[5-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]thiophen-2-yl]hex-4-ynoic acid
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C29H32O6S2
 1
1
EC50 > 10000 nM
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CP0104146
2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid
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C29H32O7S
 1
1
EC50 > 10000 nM
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CP0558597
8-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]octanoic acid
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C25H28F4O5
 1
1
EC50 = 24040 nM
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CP0438830
7-[4-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-2,6-difluorophenoxy]heptanoic acid
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C24H26F4O5
 1
1
EC50 > 100000 nM
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Biochemical Assays
Compound ID Compound Name Compound Formula
CP0048255
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid
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C18H12F4O4
 2
1 EC50 = 16 nM
2 EC50 = 63 nM
CP0085978
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]-2,6-dimethylphenoxy]butanoic acid
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C19H18ClF3O4
 2
1 EC50 = 94 nM
2 EC50 = 1100 nM
CP0145583
3-[4-[[5-fluoro-2-(4-methylphenyl)phenyl]methoxy]phenyl]propanoic acid
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C23H21FO3
 1
1 EC50 = 471 nM
CP0153669
3-[4-[2-[2-(cyanomethyl)phenyl]ethynyl]phenyl]propanoic acid
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C19H15NO2
 1
1 EC50 = 4786.3 nM
Clinical Information about the Protein
Target 1 ( G-protein coupled receptor 120 (GPR120) )
Target Type Literature-reported Target
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT03121 Free fatty acid receptor 4 Mus musculus, Mouse
PT05503 Free fatty acid receptor 4 Rattus norvegicus, Rat