FFAR4_MOUSE
ID FFAR4_MOUSE Reviewed; 361 AA.
AC Q7TMA4;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Free fatty acid receptor 4;
DE AltName: Full=G-protein coupled receptor 120;
DE AltName: Full=G-protein coupled receptor GT01;
DE AltName: Full=Omega-3 fatty acid receptor 1;
GN Name=Ffar4; Synonyms=Gpr120, O3far1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14623098; DOI=10.1016/s0014-5793(03)01196-7;
RA Fredriksson R., Hoeglund P.J., Gloriam D.E.I., Lagerstroem M.C.,
RA Schioeth H.B.;
RT "Seven evolutionarily conserved human rhodopsin G protein-coupled receptors
RT lacking close relatives.";
RL FEBS Lett. 554:381-388(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=15619630; DOI=10.1038/nm1168;
RA Hirasawa A., Tsumaya K., Awaji T., Katsuma S., Adachi T., Yamada M.,
RA Sugimoto Y., Miyazaki S., Tsujimoto G.;
RT "Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion
RT through GPR120.";
RL Nat. Med. 11:90-94(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=15774482; DOI=10.1074/jbc.m412385200;
RA Katsuma S., Hatae N., Yano T., Ruike Y., Kimura M., Hirasawa A.,
RA Tsujimoto G.;
RT "Free fatty acids inhibit serum deprivation-induced apoptosis through
RT GPR120 in a murine enteroendocrine cell line STC-1.";
RL J. Biol. Chem. 280:19507-19515(2005).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=17250804; DOI=10.1016/j.bbrc.2007.01.028;
RA Gotoh C., Hong Y.H., Iga T., Hishikawa D., Suzuki Y., Song S.H., Choi K.C.,
RA Adachi T., Hirasawa A., Tsujimoto G., Sasaki S., Roh S.G.;
RT "The regulation of adipogenesis through GPR120.";
RL Biochem. Biophys. Res. Commun. 354:591-597(2007).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=19071193; DOI=10.1016/j.neulet.2008.11.056;
RA Matsumura S., Eguchi A., Mizushige T., Kitabayashi N., Tsuzuki S.,
RA Inoue K., Fushiki T.;
RT "Colocalization of GPR120 with phospholipase-Cbeta2 and alpha-gustducin in
RT the taste bud cells in mice.";
RL Neurosci. Lett. 450:186-190(2009).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND INDUCTION.
RX PubMed=20813258; DOI=10.1016/j.cell.2010.07.041;
RA Oh da Y., Talukdar S., Bae E.J., Imamura T., Morinaga H., Fan W., Li P.,
RA Lu W.J., Watkins S.M., Olefsky J.M.;
RT "GPR120 is an omega-3 fatty acid receptor mediating potent anti-
RT inflammatory and insulin-sensitizing effects.";
RL Cell 142:687-698(2010).
RN [8]
RP TISSUE SPECIFICITY, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20573884; DOI=10.1523/jneurosci.0496-10.2010;
RA Cartoni C., Yasumatsu K., Ohkuri T., Shigemura N., Yoshida R., Godinot N.,
RA le Coutre J., Ninomiya Y., Damak S.;
RT "Taste preference for fatty acids is mediated by GPR40 and GPR120.";
RL J. Neurosci. 30:8376-8382(2010).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22343897; DOI=10.1038/nature10798;
RA Ichimura A., Hirasawa A., Poulain-Godefroy O., Bonnefond A., Hara T.,
RA Yengo L., Kimura I., Leloire A., Liu N., Iida K., Choquet H., Besnard P.,
RA Lecoeur C., Vivequin S., Ayukawa K., Takeuchi M., Ozawa K., Tauber M.,
RA Maffeis C., Morandi A., Buzzetti R., Elliott P., Pouta A., Jarvelin M.R.,
RA Korner A., Kiess W., Pigeyre M., Caiazzo R., Van Hul W., Van Gaal L.,
RA Horber F., Balkau B., Levy-Marchal C., Rouskas K., Kouvatsi A.,
RA Hebebrand J., Hinney A., Scherag A., Pattou F., Meyre D., Koshimizu T.A.,
RA Wolowczuk I., Tsujimoto G., Froguel P.;
RT "Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and
RT human.";
RL Nature 483:350-354(2012).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24222669; DOI=10.1152/ajpendo.00306.2013;
RA Gong Z., Yoshimura M., Aizawa S., Kurotani R., Zigman J.M., Sakai T.,
RA Sakata I.;
RT "G protein-coupled receptor 120 signaling regulates ghrelin secretion in
RT vivo and in vitro.";
RL Am. J. Physiol. 306:E28-E35(2014).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24663807; DOI=10.1007/s00125-014-3213-0;
RA Stone V.M., Dhayal S., Brocklehurst K.J., Lenaghan C., Soerhede Winzell M.,
RA Hammar M., Xu X., Smith D.M., Morgan N.G.;
RT "GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and
RT regulates somatostatin secretion from murine islets of Langerhans.";
RL Diabetologia 57:1182-1191(2014).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=24742677; DOI=10.1074/jbc.m114.568683;
RA Suckow A.T., Polidori D., Yan W., Chon S., Ma J.Y., Leonard J.,
RA Briscoe C.P.;
RT "Alteration of the glucagon axis in GPR120 (FFAR4) knockout mice: a role
RT for GPR120 in glucagon secretion.";
RL J. Biol. Chem. 289:15751-15763(2014).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25535828; DOI=10.1210/en.2014-1653;
RA Iwasaki K., Harada N., Sasaki K., Yamane S., Iida K., Suzuki K.,
RA Hamasaki A., Nasteska D., Shibue K., Joo E., Harada T., Hashimoto T.,
RA Asakawa Y., Hirasawa A., Inagaki N.;
RT "Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K
RT cells of the upper small intestine and has a critical role in GIP secretion
RT after fat ingestion.";
RL Endocrinology 156:837-846(2015).
RN [14]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=26365922; DOI=10.1038/srep14080;
RA Gao B., Huang Q., Jie Q., Lu W.G., Wang L., Li X.J., Sun Z., Hu Y.Q.,
RA Chen L., Liu B.H., Liu J., Yang L., Luo Z.J.;
RT "GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic
RT differentiation of BMMSCs.";
RL Sci. Rep. 5:14080-14080(2015).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 347-THR--SER-361.
RX PubMed=27852822; DOI=10.1074/jbc.m116.754887;
RA Alvarez-Curto E., Inoue A., Jenkins L., Raihan S.Z., Prihandoko R.,
RA Tobin A.B., Milligan G.;
RT "Targeted Elimination of G Proteins and Arrestins Defines Their Specific
RT Contributions to Both Intensity and Duration of G Protein-coupled Receptor
RT Signaling.";
RL J. Biol. Chem. 291:27147-27159(2016).
RN [16]
RP FUNCTION, PHOSPHORYLATION AT THR-347; THR-349; SER-350; SER-357; SER-360
RP AND SER-361, MUTAGENESIS OF 347-THR--SER-361, INTERACTION WITH ARRB2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26873857; DOI=10.1124/mol.115.101949;
RA Prihandoko R., Alvarez-Curto E., Hudson B.D., Butcher A.J., Ulven T.,
RA Miller A.M., Tobin A.B., Milligan G.;
RT "Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free
RT Fatty Acid Receptor 4/G Protein-Coupled Receptor 120.";
RL Mol. Pharmacol. 89:505-520(2016).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY COLD.
RX PubMed=27853148; DOI=10.1038/ncomms13479;
RA Quesada-Lopez T., Cereijo R., Turatsinze J.V., Planavila A., Cairo M.,
RA Gavalda-Navarro A., Peyrou M., Moure R., Iglesias R., Giralt M.,
RA Eizirik D.L., Villarroya F.;
RT "The lipid sensor GPR120 promotes brown fat activation and FGF21 release
RT from adipocytes.";
RL Nat. Commun. 7:13479-13479(2016).
RN [18]
RP FUNCTION, INDUCTION BY ADRB3 AGONIST, AND DEVELOPMENTAL STAGE.
RX PubMed=29343498; DOI=10.15252/emmm.201708047;
RA Schilperoort M., van Dam A.D., Hoeke G., Shabalina I.G., Okolo A.,
RA Hanyaloglu A.C., Dib L.H., Mol I.M., Caengprasath N., Chan Y.W., Damak S.,
RA Miller A.R., Coskun T., Shimpukade B., Ulven T., Kooijman S., Rensen P.C.,
RA Christian M.;
RT "The GPR120 agonist TUG-891 promotes metabolic health by stimulating
RT mitochondrial respiration in brown fat.";
RL EMBO Mol. Med. 10:0-0(2018).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=31761534; DOI=10.1016/j.cell.2019.11.005;
RA Hilgendorf K.I., Johnson C.T., Mezger A., Rice S.L., Norris A.M.,
RA Demeter J., Greenleaf W.J., Reiter J.F., Kopinke D., Jackson P.K.;
RT "Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis.";
RL Cell 179:1289-1305(2019).
CC -!- FUNCTION: G-protein-coupled receptor for long-chain fatty acids (LCFAs)
CC with a major role in adipogenesis, energy metabolism and inflammation.
CC Signals via G-protein and beta-arrestin pathways (PubMed:27852822,
CC PubMed:26873857). LCFAs sensing initiates activation of
CC phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)),
CC inducing a variety of cellular responses via second messenger pathways
CC such as intracellular calcium mobilization, modulation of cyclic
CC adenosine monophosphate (cAMP) production, and mitogen-activated
CC protein kinases (MAPKs) (PubMed:27852822, PubMed:26873857). After LCFAs
CC binding, associates with beta-arrestin ARRB2 that acts as an adapter
CC protein coupling the receptor to specific downstream signaling
CC pathways, as well as mediating receptor endocytosis (PubMed:27852822,
CC PubMed:26873857). In response to dietary fats, plays an important role
CC in the regulation of adipocyte proliferation and differentiation
CC (PubMed:17250804, PubMed:22343897, PubMed:27853148, PubMed:29343498,
CC PubMed:31761534). Acts as a receptor for omega-3 polyunsaturated fatty
CC acids (PUFAs) at primary cilium of perivascular preadipocytes,
CC initiating an adipogenic program via cAMP and CTCF-dependent chromatin
CC remodeling that ultimately results in transcriptional activation of
CC adipogenic genes and cell cycle entry (PubMed:31761534). Induces
CC differentiation of brown and beige adipocytes probably via autocrine
CC and endocrine functions of FGF21 hormone (PubMed:27853148,
CC PubMed:29343498). Contributes to the thermogenic activation of brown
CC adipose tissue and the browning of white adipose tissue
CC (PubMed:27853148, PubMed:29343498). Activates brown adipocytes by
CC initiating intracellular calcium signaling leading to mitochondrial
CC depolarization and fission, and overall increased mitochondrial
CC respiration (PubMed:29343498). Consequently stimulates fatty acid
CC uptake and oxidation in mitochondria together with UCP1-mediated
CC thermogenic respiration, eventually reducing fat mass
CC (PubMed:29343498). Regulates bi-potential differentiation of bone
CC marrow mesenchymal stem cells toward osteoblasts or adipocytes likely
CC by up-regulating distinct integrins (PubMed:26365922). In response to
CC dietary fats regulates hormone secretion and appetite (PubMed:15619630,
CC PubMed:25535828, PubMed:24742677, PubMed:24663807, PubMed:24222669).
CC Stimulates GIP and GLP1 secretion from enteroendocrine cells as well as
CC GCG secretion in pancreatic alpha cells, thereby playing a role in the
CC regulation of blood glucose levels (PubMed:15619630, PubMed:25535828,
CC PubMed:24742677). Negatively regulates glucose-induced SST secretion in
CC pancreatic delta cells (PubMed:24663807). Mediates LCFAs inhibition of
CC GHRL secretion, an appetite-controlling hormone (PubMed:24222669). In
CC taste buds, contributes to sensing of dietary fatty acids by the
CC gustatory system (PubMed:20573884). During the inflammatory response,
CC promotes anti-inflammatory M2 macrophage differentiation in adipose
CC tissue (PubMed:20813258). Mediates the anti-inflammatory effects of
CC omega-3 PUFAs via inhibition of NLRP3 inflammasome activation (By
CC similarity). In this pathway, interacts with adapter protein ARRB2 and
CC inhibits the priming step triggered by Toll-like receptors (TLRs) at
CC the level of TAK1 and TAB1 (PubMed:20813258). Further inhibits the
CC activation step when ARRB2 directly associates with NLRP3, leading to
CC inhibition of pro-inflammatory cytokine release (By similarity).
CC Mediates LCFAs anti-apoptotic effects (PubMed:15774482).
CC {ECO:0000250|UniProtKB:Q5NUL3, ECO:0000269|PubMed:15619630,
CC ECO:0000269|PubMed:15774482, ECO:0000269|PubMed:17250804,
CC ECO:0000269|PubMed:20573884, ECO:0000269|PubMed:20813258,
CC ECO:0000269|PubMed:22343897, ECO:0000269|PubMed:24222669,
CC ECO:0000269|PubMed:24663807, ECO:0000269|PubMed:24742677,
CC ECO:0000269|PubMed:25535828, ECO:0000269|PubMed:26365922,
CC ECO:0000269|PubMed:26873857, ECO:0000269|PubMed:27852822,
CC ECO:0000269|PubMed:27853148, ECO:0000269|PubMed:29343498,
CC ECO:0000269|PubMed:31761534}.
CC -!- SUBUNIT: Interacts (via C-terminus) with ARRB2 following LCFAs
CC stimulation. {ECO:0000269|PubMed:26873857}.
CC -!- INTERACTION:
CC Q7TMA4; Q91YI4: Arrb2; NbExp=4; IntAct=EBI-2912413, EBI-994161;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20813258,
CC ECO:0000269|PubMed:26873857, ECO:0000269|PubMed:27852822}; Multi-pass
CC membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q5NUL3}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q5NUL3}; Multi-
CC pass membrane protein {ECO:0000255}. Cell projection, cilium membrane
CC {ECO:0000269|PubMed:31761534}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Sorted to late endosome/lysosome compartments upon
CC internalization (By similarity). Specifically localizes to the primary
CC cilium of undifferentiated adipocytes. Ciliary trafficking is TULP3-
CC dependent. As the cilium is lost during adipogenesis, moves to the
CC plasma membrane (PubMed:31761534). {ECO:0000250|UniProtKB:Q5NUL3,
CC ECO:0000269|PubMed:31761534}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brown and white adipose tissue
CC (PubMed:27853148, PubMed:17250804, PubMed:24222669). Expressed in
CC perivascular ciliated preadipocytes (at protein level)
CC (PubMed:31761534). Expressed in the taste buds of the circumvallate and
CC fungiform papillae, mainly in type II cells (at protein level)
CC (PubMed:19071193, PubMed:20573884). Abundant expression is detected in
CC the gastrointestinal tract (PubMed:15619630, PubMed:27853148,
CC PubMed:17250804, PubMed:24222669). Highly expressed in lung and
CC pituitary gland (PubMed:15619630, PubMed:17250804). Expressed in
CC enteroendocrine K cells of the upper small intestine (PubMed:25535828).
CC Expressed in alpha and delta cells of pancreatic islets
CC (PubMed:24742677, PubMed:24663807). Expressed in pro-inflammatory
CC CD11C-positive macrophages (PubMed:20813258). Also expressed in spleen
CC (PubMed:17250804). {ECO:0000269|PubMed:15619630,
CC ECO:0000269|PubMed:17250804, ECO:0000269|PubMed:19071193,
CC ECO:0000269|PubMed:20573884, ECO:0000269|PubMed:20813258,
CC ECO:0000269|PubMed:24222669, ECO:0000269|PubMed:24663807,
CC ECO:0000269|PubMed:24742677, ECO:0000269|PubMed:25535828,
CC ECO:0000269|PubMed:27853148, ECO:0000269|PubMed:31761534}.
CC -!- DEVELOPMENTAL STAGE: Expression detected in differentiated mature
CC adipocytes, with levels increasing during late stage adipocyte
CC differentiation (PubMed:17250804, PubMed:29343498). Low expression is
CC detected in preadipocytes, mainly localized in primary cilium
CC (PubMed:31761534). Expression level in bone marrow mesenchymal stem
CC cells is gradually increased during differentiation toward osteoblasts
CC (PubMed:26365922). {ECO:0000269|PubMed:17250804,
CC ECO:0000269|PubMed:26365922, ECO:0000269|PubMed:29343498,
CC ECO:0000269|PubMed:31761534}.
CC -!- INDUCTION: Up-regulated in response to high-fat diet in adipose tissue
CC macrophages and in hepatic Kupffer cells (PubMed:17250804,
CC PubMed:20813258). Up-regulated in response to either short- or long-
CC term cold exposure in brown adipose tissue and inguinal white adipose
CC tissue (PubMed:27853148). Up-regulated by ADRB3 agonist
CC (PubMed:29343498). {ECO:0000269|PubMed:17250804,
CC ECO:0000269|PubMed:20813258, ECO:0000269|PubMed:27853148,
CC ECO:0000269|PubMed:29343498}.
CC -!- PTM: Phosphorylated at two clusters of Ser and Thr residues located in
CC the intracellular C-terminus, a prerequisite for FFAR4 internalization
CC via an ARRB2-dependent pathway. {ECO:0000269|PubMed:26873857}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice show glucose intolerance,
CC hyperinsulinemia and display insulin (INS) resistance and a reduced
CC preference for fatty acids (PubMed:22343897, PubMed:24742677,
CC PubMed:20573884). When fed a high-fat diet, they develop obesity and
CC have fatty liver with decreased adipocyte differentiation and
CC lipogenesis, and enhanced hepatic lipogenesis (PubMed:22343897). INS
CC resistance in such mice is associated with reduced INS signaling and
CC enhanced inflammation in adipose tissue (PubMed:20813258).
CC {ECO:0000269|PubMed:20573884, ECO:0000269|PubMed:20813258,
CC ECO:0000269|PubMed:22343897, ECO:0000269|PubMed:24742677}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB115769; BAD83369.1; -; mRNA.
DR EMBL; AY288424; AAP72133.1; -; mRNA.
DR EMBL; BC053698; AAH53698.1; -; mRNA.
DR CCDS; CCDS29783.1; -.
DR RefSeq; NP_861413.1; NM_181748.2.
DR AlphaFoldDB; Q7TMA4; -.
DR SMR; Q7TMA4; -.
DR IntAct; Q7TMA4; 1.
DR STRING; 10090.ENSMUSP00000063660; -.
DR BindingDB; Q7TMA4; -.
DR ChEMBL; CHEMBL2052036; -.
DR GuidetoPHARMACOLOGY; 127; -.
DR SwissLipids; SLP:000001560; -.
DR GlyGen; Q7TMA4; 1 site.
DR iPTMnet; Q7TMA4; -.
DR PhosphoSitePlus; Q7TMA4; -.
DR PaxDb; Q7TMA4; -.
DR PRIDE; Q7TMA4; -.
DR ProteomicsDB; 271692; -.
DR Antibodypedia; 16549; 363 antibodies from 36 providers.
DR DNASU; 107221; -.
DR Ensembl; ENSMUST00000067098; ENSMUSP00000063660; ENSMUSG00000054200.
DR GeneID; 107221; -.
DR KEGG; mmu:107221; -.
DR UCSC; uc008hjc.1; mouse.
DR CTD; 338557; -.
DR MGI; MGI:2147577; Ffar4.
DR VEuPathDB; HostDB:ENSMUSG00000054200; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230390; -.
DR HOGENOM; CLU_061487_0_0_1; -.
DR InParanoid; Q7TMA4; -.
DR OMA; TLPLCCF; -.
DR OrthoDB; 1057232at2759; -.
DR PhylomeDB; Q7TMA4; -.
DR TreeFam; TF336844; -.
DR Reactome; R-MMU-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 107221; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Ffar4; mouse.
DR PRO; PR:Q7TMA4; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q7TMA4; protein.
DR Bgee; ENSMUSG00000054200; Expressed in brown adipose tissue and 47 other tissues.
DR ExpressionAtlas; Q7TMA4; baseline and differential.
DR Genevisible; Q7TMA4; MM.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; ISO:MGI.
DR GO; GO:0005504; F:fatty acid binding; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:MGI.
DR GO; GO:0008527; F:taste receptor activity; IMP:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IMP:CACAO.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0036321; P:ghrelin secretion; IMP:UniProtKB.
DR GO; GO:0046879; P:hormone secretion; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0090275; P:negative regulation of somatostatin secretion; IMP:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0070094; P:positive regulation of glucagon secretion; IMP:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; IDA:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Differentiation; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Inflammatory response;
KW Lipid-binding; Lysosome; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..361
FT /note="Free fatty acid receptor 4"
FT /id="PRO_0000069611"
FT TOPO_DOM 1..45
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..98
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..103
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..204
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..225
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..295
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 347
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:26873857"
FT MOD_RES 349
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:26873857"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26873857"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26873857"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:26873857"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26873857"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 111..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 347..361
FT /note="TDTSVRRNDLSVISS->ADAAVRRNDLAVIAA: Impairs LCFA-
FT mediated phosphorylation and interaction with ARRB2."
FT /evidence="ECO:0000269|PubMed:26873857,
FT ECO:0000269|PubMed:27852822"
SQ SEQUENCE 361 AA; 40813 MW; D3A3F0BEB55F7B7B CRC64;
MSPECAQTTG PGPSHTLDQV NRTHFPFFSD VKGDHRLVLS VVETTVLGLI FVVSLLGNVC
ALVLVARRRR RGATASLVLN LFCADLLFTS AIPLVLVVRW TEAWLLGPVV CHLLFYVMTM
SGSVTILTLA AVSLERMVCI VRLRRGLSGP GRRTQAALLA FIWGYSALAA LPLCILFRVV
PQRLPGGDQE IPICTLDWPN RIGEISWDVF FVTLNFLVPG LVIVISYSKI LQITKASRKR
LTLSLAYSES HQIRVSQQDY RLFRTLFLLM VSFFIMWSPI IITILLILIQ NFRQDLVIWP
SLFFWVVAFT FANSALNPIL YNMSLFRNEW RKIFCCFFFP EKGAIFTDTS VRRNDLSVIS
S
