ID FFAR4_HUMAN Reviewed; 377 AA. AC Q5NUL3; Q495H1; Q5VY25; Q5VY26; Q7Z605; Q86SM7; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2005, sequence version 2. DT 11-DEC-2019, entry version 132. 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; Synonyms=GPR120, 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 TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. 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 [8] 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 [9] RP INVOLVEMENT IN BMIQ10, VARIANTS CYS-67 AND HIS-270, AND ASSOCIATION OF RP VARIANT HIS-270 WITH RISK OF OBESITY. 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: Receptor for medium and long-chain free fatty acids (FFAs). CC Signals via a G(q)/G(11)-coupled pathway. Acts as a receptor for omega- CC 3 fatty acids and mediates robust anti-inflammatory effects, CC particularly in macrophages and fat cells. The anti-inflammatory CC effects involve inhibition of TAK1 through a beta-arrestin 2 CC (ARRB2)/TAB1-dependent effect, but independent of the G(q)/G(11)- CC coupled pathway. Mediates potent insulin sensitizing and antidiabetic CC effects by repressing macrophage-induced tissue inflammation. May CC mediate the taste of fatty acids. Mediates FFA-induced inhibition of CC apoptosis in enteroendocrine cells. May play a role in the regulation CC of adipocyte development and differentiation. CC {ECO:0000269|PubMed:15619630}. CC -!- SUBUNIT: Interacts with ARRB2 following docosahexaenoic acid (DHA) CC stimulation. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane CC protein {ECO:0000250}. Note=Colocalized with ARRB2 following DHA CC treatment. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5NUL3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5NUL3-2; Sequence=VSP_013684; CC -!- TISSUE SPECIFICITY: Abundant expression in the intestinal tract. Highly CC expressed in adipose tissue, small intestine and pancreas. CC {ECO:0000269|PubMed:15619630, ECO:0000269|PubMed:17250804}. CC -!- DEVELOPMENTAL STAGE: Expression detected in differentiated adipocytes CC but not in preadipocytes. {ECO:0000269|PubMed:17250804}. CC -!- PTM: Phosphorylated. FFA stimulation facilitates phosphorylation. CC {ECO:0000269|PubMed:20471368}. 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 -!- MISCELLANEOUS: It has been shown that FFA alpha-linolenic acid CC stimulates secretion of glucagon-like peptide 1 (GLP-1) from the CC gastro-intestinal tract (PubMed:15619630). However, this ligand is an CC agonist of both FFAR4 and FFAR1 and the latter has been shown to CC mediate GLP-1 release too (PubMed:18519800). So the precise role of CC FFAR4 in mediating needs to be confirmed. CC {ECO:0000305|PubMed:15619630}. CC -!- MISCELLANEOUS: [Isoform 1]: Specific to human. 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 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 iPTMnet; Q5NUL3; -. DR PhosphoSitePlus; Q5NUL3; -. DR BioMuta; FFAR4; -. DR DMDM; 82581671; -. DR jPOST; Q5NUL3; -. DR PaxDb; Q5NUL3; -. DR PeptideAtlas; Q5NUL3; -. DR PRIDE; Q5NUL3; -. DR ProteomicsDB; 63598; -. [Q5NUL3-1] DR ProteomicsDB; 63599; -. [Q5NUL3-2] DR Ensembl; ENST00000371481; ENSP00000360536; ENSG00000186188. [Q5NUL3-2] DR Ensembl; ENST00000371483; ENSP00000360538; ENSG00000186188. [Q5NUL3-1] DR GeneID; 338557; -. DR KEGG; hsa:338557; -. DR UCSC; uc010qnt.2; human. [Q5NUL3-1] DR CTD; 338557; -. DR DisGeNET; 338557; -. DR EuPathDB; HostDB:ENSG00000186188.10; -. DR GeneCards; FFAR4; -. DR HGNC; HGNC:19061; FFAR4. DR HPA; HPA042563; -. DR MalaCards; FFAR4; -. DR MIM; 607514; phenotype. DR MIM; 609044; gene. DR neXtProt; NX_Q5NUL3; -. DR OpenTargets; ENSG00000186188; -. DR PharmGKB; PA134924595; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR GeneTree; ENSGT00970000193367; -. DR InParanoid; Q5NUL3; -. DR KO; K08425; -. DR OMA; MWSPIIV; -. DR OrthoDB; 1057232at2759; -. DR PhylomeDB; Q5NUL3; -. DR TreeFam; TF336844; -. 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 SIGNOR; Q5NUL3; -. 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 74 organ(s), highest expression level in adenohypophysis. DR ExpressionAtlas; Q5NUL3; baseline and differential. DR Genevisible; Q5NUL3; HS. DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005504; F:fatty acid binding; ISS:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central. DR GO; GO:0008527; F:taste receptor activity; IBA:GO_Central. DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0046879; P:hormone secretion; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0050710; P:negative regulation of cytokine secretion; ISS:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0010827; P:regulation of glucose transmembrane transport; ISS: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 Alternative splicing; Cell membrane; G-protein coupled receptor; KW Glycoprotein; Lipid-binding; Membrane; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..377 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..284 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 285..305 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 306..311 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 312..332 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 333..377 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT COMPBIAS 67..71 FT /note="Poly-Arg" FT CARBOHYD 21 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 233..248 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12679517, FT ECO:0000303|PubMed:15489334" FT /id="VSP_013684" 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 270 FT /note="R -> H (polymorphism associated with increased risk FT of obesity; dbSNP:rs116454156)" FT /evidence="ECO:0000269|PubMed:22343897" FT /id="VAR_067800" FT CONFLICT 67 FT /note="Missing (in Ref. 1; AAP72126)" FT /evidence="ECO:0000305" FT CONFLICT 274 FT /note="Q -> H (in Ref. 2; BAD83368)" FT /evidence="ECO:0000305" FT CONFLICT 297 FT /note="I -> T (in Ref. 2; BAD83368)" FT /evidence="ECO:0000305" SQ SEQUENCE 377 AA; 42241 MW; 28BB8C3A939A7EFF CRC64; MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFIS AIPLVLAVRW TEAWLLGPVA CHLLFYVMTL SGSVTILTLA AVSLERMVCI VHLQRGVRGP GRRARAVLLA LIWGYSAVAA LPLCVFFRVV PQRLPGADQE ISICTLIWPT IPGEISWDVS FVTLNFLVPG LVIVISYSKI LQTSEHLLDA RAVVTHSEIT KASRKRLTVS LAYSESHQIR VSQQDFRLFR TLFLLMVSFF IMWSPIIITI LLILIQNFKQ DLVIWPSLFF WVVAFTFANS ALNPILYNMT LCRNEWKKIF CCFWFPEKGA ILTDTSVKRN DLSIISG //