ID FFAR4_HUMAN Reviewed; 361 AA. AC Q5NUL3; Q495H1; Q5VY25; Q5VY26; Q7Z605; Q86SM7; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 22-APR-2020, sequence version 3. DT 27-MAR-2024, entry version 154. DE RecName: Full=Free fatty acid receptor 4; DE AltName: Full=G-protein coupled receptor 120; DE AltName: Full=G-protein coupled receptor 129; DE AltName: Full=G-protein coupled receptor GT01; DE AltName: Full=G-protein coupled receptor PGR4; DE AltName: Full=Omega-3 fatty acid receptor 1; GN Name=FFAR4 {ECO:0000312|HGNC:HGNC:19061}; GN Synonyms=GPR120 {ECO:0000303|PubMed:22282525}, GPR129, O3FAR1, PGR4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP VARIANT CYS-67. 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 GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 49-312 (ISOFORM 2). RX PubMed=12679517; DOI=10.1073/pnas.0230374100; RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E., RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C., RA Bergmann J.E., Gaitanaris G.A.; RT "The G protein-coupled receptor repertoires of human and mouse."; RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003). RN [7] RP PHOSPHORYLATION. RX PubMed=20471368; DOI=10.1016/j.bbrc.2010.05.057; RA Burns R.N., Moniri N.H.; RT "Agonism with the omega-3 fatty acids alpha-linolenic acid and RT docosahexaenoic acid mediates phosphorylation of both the short and long RT isoforms of the human GPR120 receptor."; RL Biochem. Biophys. Res. Commun. 396:1030-1035(2010). RN [8] RP FUNCTION (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), RP INTERACTION WITH ARRB2 (ISOFORMS 1 AND 2), AND MUTAGENESIS OF ARG-99 AND RP ARG-178. RX PubMed=22282525; DOI=10.1124/mol.111.077388; RA Watson S.J., Brown A.J., Holliday N.D.; RT "Differential signaling by splice variants of the human free fatty acid RT receptor GPR120."; RL Mol. Pharmacol. 81:631-642(2012). RN [9] RP FUNCTION. RX PubMed=23809162; DOI=10.1016/j.immuni.2013.05.015; RA Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., RA Guarda G., Tian Z., Tschopp J., Zhou R.; RT "Omega-3 fatty acids prevent inflammation and metabolic disorder through RT inhibition of NLRP3 inflammasome activation."; RL Immunity 38:1154-1163(2013). RN [10] RP FUNCTION (ISOFORM 2), AND TISSUE SPECIFICITY (ISOFORM 2). 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 [11] RP FUNCTION (ISOFORM 2), INTERACTION WITH ARRB2 (ISOFORM 2), PHOSPHORYLATION RP AT THR-347; THR-349; SER-350; SER-357 AND SER-360, AND MUTAGENESIS OF RP 347-THR--SER-360. RX PubMed=24817122; DOI=10.1074/jbc.m114.568816; RA Butcher A.J., Hudson B.D., Shimpukade B., Alvarez-Curto E., Prihandoko R., RA Ulven T., Milligan G., Tobin A.B.; RT "Concomitant action of structural elements and receptor phosphorylation RT determines arrestin-3 interaction with the free fatty acid receptor FFA4."; RL J. Biol. Chem. 289:18451-18465(2014). RN [12] RP FUNCTION (ISOFORM 2). 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 [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. 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). RN [14] RP INVOLVEMENT IN BMIQ10, VARIANTS CYS-67 AND HIS-254, ASSOCIATION OF VARIANT RP HIS-254 WITH RISK OF OBESITY, 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). CC -!- FUNCTION: [Isoform 2]: G-protein-coupled receptor for long-chain fatty CC acids (LCFAs) with a major role in adipogenesis, energy metabolism and CC inflammation. Signals via G-protein and beta-arrestin pathways CC (PubMed:22282525, PubMed:24742677, PubMed:27852822, PubMed:24817122, CC PubMed:22343897). 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:22343897, CC PubMed:22282525, PubMed:24742677). After LCFAs binding, associates with CC beta-arrestin ARRB2 that acts as an adapter protein coupling the CC receptor to specific downstream signaling pathways, as well as CC mediating receptor endocytosis (PubMed:22282525, PubMed:24817122). In CC response to dietary fats, plays an important role in the regulation of CC adipocyte proliferation and differentiation (By similarity). Acts as a CC receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary CC cilium of perivascular preadipocytes, initiating an adipogenic program CC via cAMP and CTCF-dependent chromatin remodeling that ultimately CC results in transcriptional activation of adipogenic genes and cell CC cycle entry (By similarity). Induces differentiation of brown CC adipocytes probably via autocrine and endocrine functions of FGF21 CC hormone (By similarity). Activates brown adipocytes by initiating CC intracellular calcium signaling that leads to mitochondrial CC depolarization and fission, and overall increased mitochondrial CC respiration (By similarity). Consequently stimulates fatty acid uptake CC and oxidation in mitochondria together with UCP1-mediated thermogenic CC respiration, eventually reducing fat mass (By similarity). Regulates CC bi-potential differentiation of bone marrow mesenchymal stem cells CC toward osteoblasts or adipocytes likely by up-regulating distinct CC integrins (By similarity). In response to dietary fats regulates CC hormone secretion and appetite (By similarity). Stimulates GIP and GLP1 CC secretion from enteroendocrine cells as well as GCG secretion in CC pancreatic alpha cells, thereby playing a role in the regulation of CC blood glucose levels (By similarity). Negatively regulates glucose- CC induced SST secretion in pancreatic delta cells (By similarity). CC Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling CC hormone (By similarity). In taste buds, contributes to sensing of CC dietary fatty acids by the gustatory system (By similarity). During the CC inflammatory response, promotes anti-inflammatory M2 macrophage CC differentiation in adipose tissue (By similarity). Mediates the anti- CC inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 CC inflammasome activation (PubMed:23809162). In this pathway, interacts CC with adapter protein ARRB2 and inhibits the priming step triggered by CC Toll-like receptors (TLRs) at the level of TAK1 and TAB1 (By CC similarity). Further inhibits the activation step when ARRB2 directly CC associates with NLRP3, leading to inhibition of pro-inflammatory CC cytokine release (PubMed:23809162). Mediates LCFAs anti-apoptotic CC effects (By similarity). {ECO:0000250|UniProtKB:Q7TMA4, CC ECO:0000269|PubMed:22282525, ECO:0000269|PubMed:22343897, CC ECO:0000269|PubMed:23809162, ECO:0000269|PubMed:24742677, CC ECO:0000269|PubMed:24817122, ECO:0000269|PubMed:27852822}. CC -!- FUNCTION: [Isoform 1]: Receptor for LCFAs decoupled from G-protein CC signaling. May signal through beta-arrestin pathway. After LCFAs CC binding, associates with beta-arrestin ARRB2 that may act as an adapter CC protein coupling the receptor to specific downstream signaling CC pathways, as well as mediating receptor endocytosis. CC {ECO:0000269|PubMed:22282525}. CC -!- SUBUNIT: [Isoform 1]: Interacts (via C-terminus) with ARRB2 following CC LCFAs stimulation. {ECO:0000269|PubMed:22282525}. CC -!- SUBUNIT: [Isoform 2]: Interacts (via C-terminus) with ARRB2 following CC LCFAs stimulation. {ECO:0000269|PubMed:22282525, CC ECO:0000269|PubMed:24817122}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:22282525}; Multi-pass membrane protein CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:22282525}; Multi- CC pass membrane protein {ECO:0000255}. Lysosome membrane CC {ECO:0000269|PubMed:22282525}; Multi-pass membrane protein CC {ECO:0000255}. Note=Sorted to late endosome/lysosome compartments upon CC internalization. {ECO:0000269|PubMed:22282525}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane CC {ECO:0000269|PubMed:22282525}; Multi-pass membrane protein CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:22282525}; Multi- CC pass membrane protein {ECO:0000255}. Lysosome membrane CC {ECO:0000269|PubMed:22282525}; Multi-pass membrane protein CC {ECO:0000255}. Cell projection, cilium membrane CC {ECO:0000305|PubMed:31761534}; Multi-pass membrane protein CC {ECO:0000255}. Note=Sorted to late endosome/lysosome compartments upon CC internalization (PubMed:22282525). Specifically localizes to the CC primary cilium of undifferentiated adipocytes. Ciliary trafficking is CC TULP3-dependent. As the cilium is lost during adipogenesis, moves to CC the plasma membrane (Probable). {ECO:0000269|PubMed:22282525, CC ECO:0000305|PubMed:31761534}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; CC IsoId=Q5NUL3-2; Sequence=Displayed; CC Name=1; CC IsoId=Q5NUL3-1; Sequence=VSP_060543; CC -!- TISSUE SPECIFICITY: [Isoform 2]: The predominant isoform in human CC tissues. Expressed in adipose tissue, pancreatic islets, lung and CC brain. Expressed in alpha cells of pancreatic islets (PubMed:24742677). CC Expressed in primary cilia of perivascular preadipocytes of white CC adipose tissue (at protein level) (PubMed:31761534). CC {ECO:0000269|PubMed:24742677, ECO:0000269|PubMed:31761534}. CC -!- TISSUE SPECIFICITY: Abundant expression in the intestinal tract. CC Expressed in colonic intraepithelial neuroendocrine cells. CC {ECO:0000269|PubMed:15619630}. CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Low expression is detected in CC preadipocytes, mainly localized in primary cilium. CC {ECO:0000305|PubMed:31761534}. 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:20471368, CC ECO:0000269|PubMed:24817122}. CC -!- POLYMORPHISM: Genetic variations in FFAR4 define the body mass index CC quantitative trait locus 10 (BMIQ10) [MIM:607514]. Variance in body CC mass index is a susceptibility factor for obesity. CC {ECO:0000269|PubMed:22343897}. 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; AY288417; AAP72126.1; -; mRNA. DR EMBL; AB115768; BAD83368.1; -; mRNA. DR EMBL; AL356214; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50069.1; -; Genomic_DNA. DR EMBL; BC101175; AAI01176.1; -; mRNA. DR EMBL; AY255573; AAO85085.1; -; mRNA. DR CCDS; CCDS31248.1; -. [Q5NUL3-1] DR CCDS; CCDS55720.1; -. [Q5NUL3-2] DR RefSeq; NP_001182684.1; NM_001195755.1. [Q5NUL3-2] DR RefSeq; NP_859529.2; NM_181745.3. [Q5NUL3-1] DR PDB; 8G59; EM; 2.64 A; R=1-361. DR PDB; 8H4I; EM; 3.06 A; R=1-361. DR PDB; 8H4K; EM; 3.10 A; R=1-361. DR PDB; 8H4L; EM; 3.07 A; R=1-361. DR PDB; 8ID3; EM; 3.10 A; R=1-361. DR PDB; 8ID4; EM; 3.10 A; R=1-361. DR PDB; 8ID6; EM; 2.80 A; R=1-361. DR PDB; 8ID8; EM; 3.00 A; R=1-361. DR PDB; 8ID9; EM; 3.00 A; R=1-361. DR PDB; 8IYS; EM; 2.95 A; R=1-361. DR PDBsum; 8G59; -. DR PDBsum; 8H4I; -. DR PDBsum; 8H4K; -. DR PDBsum; 8H4L; -. DR PDBsum; 8ID3; -. DR PDBsum; 8ID4; -. DR PDBsum; 8ID6; -. DR PDBsum; 8ID8; -. DR PDBsum; 8ID9; -. DR PDBsum; 8IYS; -. DR AlphaFoldDB; Q5NUL3; -. DR EMDB; EMD-29736; -. DR EMDB; EMD-34478; -. DR EMDB; EMD-34479; -. DR EMDB; EMD-34480; -. DR EMDB; EMD-35356; -. DR EMDB; EMD-35357; -. DR EMDB; EMD-35358; -. DR EMDB; EMD-35359; -. DR EMDB; EMD-35360; -. DR EMDB; EMD-35830; -. DR SMR; Q5NUL3; -. DR IntAct; Q5NUL3; 1. DR STRING; 9606.ENSP00000360538; -. DR BindingDB; Q5NUL3; -. DR ChEMBL; CHEMBL5339; -. DR DrugBank; DB05532; BMS-488043. DR DrugBank; DB13961; Fish oil. DR DrugBank; DB05793; PRO-542. DR DrugCentral; Q5NUL3; -. DR GuidetoPHARMACOLOGY; 127; -. DR SwissLipids; SLP:000001562; -. [Q5NUL3-2] DR TCDB; 9.A.14.13.29; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; Q5NUL3; 1 site, No reported glycans. DR GlyGen; Q5NUL3; 1 site. DR iPTMnet; Q5NUL3; -. DR PhosphoSitePlus; Q5NUL3; -. DR SwissPalm; Q5NUL3; -. DR BioMuta; FFAR4; -. DR DMDM; 82581671; -. DR MassIVE; Q5NUL3; -. DR PaxDb; 9606-ENSP00000360538; -. DR PeptideAtlas; Q5NUL3; -. DR ProteomicsDB; 63598; -. [Q5NUL3-1] DR ProteomicsDB; 63599; -. [Q5NUL3-2] DR Antibodypedia; 16549; 417 antibodies from 36 providers. DR DNASU; 338557; -. DR Ensembl; ENST00000371481.9; ENSP00000360536.5; ENSG00000186188.11. [Q5NUL3-2] DR Ensembl; ENST00000371483.8; ENSP00000360538.4; ENSG00000186188.11. [Q5NUL3-1] DR GeneID; 338557; -. DR KEGG; hsa:338557; -. DR MANE-Select; ENST00000371481.9; ENSP00000360536.5; NM_001195755.2; NP_001182684.1. DR UCSC; uc010qnt.2; human. [Q5NUL3-2] DR AGR; HGNC:19061; -. DR CTD; 338557; -. DR DisGeNET; 338557; -. DR GeneCards; FFAR4; -. DR HGNC; HGNC:19061; FFAR4. DR HPA; ENSG00000186188; Group enriched (adipose tissue, intestine, lung, pituitary gland). DR MalaCards; FFAR4; -. DR MIM; 607514; phenotype. DR MIM; 609044; gene. DR neXtProt; NX_Q5NUL3; -. DR OpenTargets; ENSG00000186188; -. DR PharmGKB; PA134924595; -. DR VEuPathDB; HostDB:ENSG00000186188; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01070000253744; -. DR HOGENOM; CLU_061487_0_0_1; -. DR InParanoid; Q5NUL3; -. DR OMA; CHMLFYV; -. DR OrthoDB; 5310066at2759; -. DR PhylomeDB; Q5NUL3; -. DR TreeFam; TF336844; -. DR PathwayCommons; Q5NUL3; -. DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1). DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-444209; Free fatty acid receptors. DR SignaLink; Q5NUL3; -. DR SIGNOR; Q5NUL3; -. DR BioGRID-ORCS; 338557; 17 hits in 1154 CRISPR screens. DR ChiTaRS; FFAR4; human. DR GeneWiki; GPR120; -. DR GenomeRNAi; 338557; -. DR Pharos; Q5NUL3; Tchem. DR PRO; PR:Q5NUL3; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q5NUL3; Protein. DR Bgee; ENSG00000186188; Expressed in mucosa of sigmoid colon and 94 other cell types or tissues. DR ExpressionAtlas; Q5NUL3; baseline and differential. 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; IEA:Ensembl. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:1990763; F:arrestin family protein binding; IDA:UniProtKB. DR GO; GO:0005504; F:fatty acid binding; ISS:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0042277; F:peptide binding; IBA:GO_Central. DR GO; GO:0008527; F:taste receptor activity; IBA:GO_Central. DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB. DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0036321; P:ghrelin secretion; ISS:UniProtKB. DR GO; GO:0046879; P:hormone secretion; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB. DR GO; GO:0090275; P:negative regulation of somatostatin secretion; ISS: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; IEA:Ensembl. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISS:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0070094; P:positive regulation of glucagon secretion; ISS:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0010827; P:regulation of glucose transmembrane transport; ISS:UniProtKB. DR GO; GO:0050872; P:white fat cell differentiation; IDA:UniProtKB. DR CDD; cd00637; 7tm_classA_rhodopsin-like; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24241:SF67; FREE FATTY ACID RECEPTOR 4; 1. DR PANTHER; PTHR24241; NEUROPEPTIDE RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; Q5NUL3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Differentiation; Disulfide bond; Endosome; G-protein coupled receptor; KW Glycoprotein; Inflammatory response; Lipid-binding; Lysosome; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..361 FT /note="Free fatty acid receptor 4" FT /id="PRO_0000069610" 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..112 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 113..133 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 134..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:24817122" FT MOD_RES 349 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:24817122" FT MOD_RES 350 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:24817122" FT MOD_RES 357 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:24817122" FT MOD_RES 360 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:24817122" 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 VAR_SEQ 232 FT /note="Q -> QTSEHLLDARAVVTHSE (in isoform 1)" FT /evidence="ECO:0000269|PubMed:12679517, FT ECO:0000269|PubMed:15489334" FT /id="VSP_060543" FT VARIANT 67 FT /note="R -> C (in dbSNP:rs61866610)" FT /evidence="ECO:0000269|PubMed:15619630, FT ECO:0000269|PubMed:22343897" FT /id="VAR_067799" FT VARIANT 254 FT /note="R -> H (probable risk factor for obesity; FT significantly decreases LCFA-induced intracellular calcium FT release.; dbSNP:rs116454156)" FT /evidence="ECO:0000269|PubMed:22343897" FT /id="VAR_067800" FT MUTAGEN 99 FT /note="R->A: Impairs LCFA-induced intracellular calcium FT release." FT /evidence="ECO:0000269|PubMed:22282525" FT MUTAGEN 178 FT /note="R->A: Has no effect on LCFA-induced intracellular FT calcium release." FT /evidence="ECO:0000269|PubMed:22282525" FT MUTAGEN 347..360 FT /note="TDTSVKRNDLSIIS->AAAAVKRNALAIIA: Impairs FT LCFA-mediated phosphorylation and interaction with ARRB2." FT /evidence="ECO:0000269|PubMed:24817122" FT CONFLICT 67 FT /note="Missing (in Ref. 1; AAP72126)" FT /evidence="ECO:0000305" FT CONFLICT 258 FT /note="Q -> H (in Ref. 2; BAD83368)" FT /evidence="ECO:0000305" FT CONFLICT 281 FT /note="I -> T (in Ref. 2; BAD83368)" FT /evidence="ECO:0000305" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 43..69 FT /evidence="ECO:0007829|PDB:8G59" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:8H4K" FT HELIX 78..90 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 92..100 FT /evidence="ECO:0007829|PDB:8G59" FT STRAND 101..103 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 110..141 FT /evidence="ECO:0007829|PDB:8G59" FT TURN 143..146 FT /evidence="ECO:0007829|PDB:8H4K" FT HELIX 153..168 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 169..171 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 172..175 FT /evidence="ECO:0007829|PDB:8G59" FT STRAND 176..182 FT /evidence="ECO:0007829|PDB:8G59" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:8ID6" FT STRAND 191..196 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 202..243 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 249..291 FT /evidence="ECO:0007829|PDB:8G59" FT HELIX 300..320 FT /evidence="ECO:0007829|PDB:8G59" FT TURN 321..324 FT /evidence="ECO:0007829|PDB:8H4K" SQ SEQUENCE 361 AA; 40494 MW; E90BD5D64D9E6E78 CRC64; MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFIS AIPLVLAVRW TEAWLLGPVA CHLLFYVMTL SGSVTILTLA AVSLERMVCI VHLQRGVRGP GRRARAVLLA LIWGYSAVAA LPLCVFFRVV PQRLPGADQE ISICTLIWPT IPGEISWDVS FVTLNFLVPG LVIVISYSKI LQITKASRKR LTVSLAYSES HQIRVSQQDF RLFRTLFLLM VSFFIMWSPI IITILLILIQ NFKQDLVIWP SLFFWVVAFT FANSALNPIL YNMTLCRNEW KKIFCCFWFP EKGAILTDTS VKRNDLSIIS G //