Ffar4
entrez
107221
canonical
uniprot
Q7TMA4
canonical
ensembl
ENSMUSG00000054200
resolver
ensp
ENSMUSP00000063660
resolver
enst
ENSMUST00000067098
resolver
genesymbol
Ffar4
resolver
genesymbol_syn
Gpr120
resolver
genesymbol_syn
O3far1
resolver
uniprot
Q3V2S5
resolver
uniprot_entry
FFAR4_MOUSE
resolver
uniprot_entry
Q3V2S5_MOUSE
resolver
amino_acid_sequence
MSPECAQTTGPGPSHTLDQVNRTHFPFFSDVKGDHRLVLSVVETTVLGLIFVVSLLGNVCALVLVARRRRRGATASLVLNLFCADLLFTSAIPLVLVVRWTEAWLLGPVVCHLLFYVMTMSGSVTILTLAAVSLERMVCIVRLRRGLSGPGRRTQAALLAFIWGYSALAALPLCILFRVVPQRLPGGDQEIPICTLDWPNRIGEISWDVFFVTLNFLVPGLVIVISYSKILQITKASRKRLTLSLAYSESHQIRVSQQDYRLFRTLFLLMVSFFIMWSPIIITILLILIQNFRQDLVIWPSLFFWVVAFTFANSALNPILYNMSLFRNEWRKIFCCFFFPEKGAIFTDTSVRRNDLSVISS
uniprot
proteins
function
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:26873857, 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:26873857, 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:26873857, PubMed:27852822). 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:24222669, PubMed:24663807, PubMed:24742677, PubMed:25535828). 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:24742677, PubMed:25535828). 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). Mediates VLCFAs-dependent liver-to-adipose tissue signaling and adipose tissue thermogenesis. {ECO:0000250|UniProtKB:Q5NUL3, ECO:0000269|PubMed:15619630, ECO:0000269|PubMed:15774482, ECO:0000269|PubMed:17250804, ECO:0000269|PubMed:20573884, ECO:0000269|PubMed:20813258, ECO:0000269|PubMed:22343897, ECO:0000269|PubMed:24222669, ECO:0000269|PubMed:24663807, ECO:0000269|PubMed:24742677, ECO:0000269|PubMed:25535828, ECO:0000269|PubMed:26365922, ECO:0000269|PubMed:26873857, ECO:0000269|PubMed:27852822, ECO:0000269|PubMed:27853148, ECO:0000269|PubMed:29343498, ECO:0000269|PubMed:31761534, ECO:0000269|PubMed:38760332}.
uniprot
proteins
mass_dalton
40813
uniprot
proteins
mutagenesis
MUTAGEN 347..361; /note="TDTSVRRNDLSVISS->ADAAVRRNDLAVIAA: Impairs LCFA-mediated phosphorylation and interaction with ARRB2."; /evidence="ECO:0000269|PubMed:26873857, ECO:0000269|PubMed:27852822
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at two clusters of Ser and Thr residues located in the intracellular C-terminus, a prerequisite for FFAR4 internalization via an ARRB2-dependent pathway. {ECO:0000269|PubMed:26873857}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
14623098
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15619630
uniprot
proteins
pubmed
15774482
uniprot
proteins
pubmed
17250804
uniprot
proteins
pubmed
19071193
uniprot
proteins
pubmed
20573884
uniprot
proteins
pubmed
20813258
uniprot
proteins
pubmed
22343897
uniprot
proteins
pubmed
24222669
uniprot
proteins
pubmed
24663807
uniprot
proteins
pubmed
24742677
uniprot
proteins
pubmed
25535828
uniprot
proteins
pubmed
26365922
uniprot
proteins
pubmed
26873857
uniprot
proteins
pubmed
27852822
uniprot
proteins
pubmed
27853148
uniprot
proteins
pubmed
29343498
uniprot
proteins
pubmed
31761534
uniprot
proteins
pubmed
38760332
uniprot
proteins
sequence_length
361
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20813258, ECO:0000269|PubMed:26873857, ECO:0000269|PubMed:27852822}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:Q5NUL3}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q5NUL3}; Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium membrane {ECO:0000269|PubMed:31761534}; Multi-pass membrane protein {ECO:0000255}. Note=Sorted to late endosome/lysosome compartments upon internalization (By similarity). Specifically localizes to the primary cilium of undifferentiated adipocytes. Ciliary trafficking is TULP3-dependent. As the cilium is lost during adipogenesis, moves to the plasma membrane (PubMed:31761534). {ECO:0000250|UniProtKB:Q5NUL3, ECO:0000269|PubMed:31761534}.
uniprot
proteins
transmembrane_region
TRANSMEM 46..66; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 78..98; /note="Helical; Name=2"; /evidence="ECO:0000255"; TRANSMEM 104..124; /note="Helical; Name=3"; /evidence="ECO:0000255"; TRANSMEM 157..177; /note="Helical; Name=4"; /evidence="ECO:0000255"; TRANSMEM 205..225; /note="Helical; Name=5"; /evidence="ECO:0000255"; TRANSMEM 269..289; /note="Helical; Name=6"; /evidence="ECO:0000255"; TRANSMEM 296..316; /note="Helical; Name=7"; /evidence="ECO:0000255
uniprot
proteins