FFAR4_HUMAN
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 03-AUG-2022, entry version 145.
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 AlphaFoldDB; Q5NUL3; -.
DR SMR; Q5NUL3; -.
DR STRING; 9606.ENSP00000360538; -.
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 GlyGen; Q5NUL3; 1 site.
DR iPTMnet; Q5NUL3; -.
DR PhosphoSitePlus; Q5NUL3; -.
DR BioMuta; FFAR4; -.
DR DMDM; 82581671; -.
DR PaxDb; Q5NUL3; -.
DR PeptideAtlas; Q5NUL3; -.
DR PRIDE; Q5NUL3; -.
DR ProteomicsDB; 63598; -. [Q5NUL3-1]
DR ProteomicsDB; 63599; -. [Q5NUL3-2]
DR Antibodypedia; 16549; 363 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 CTD; 338557; -.
DR DisGeNET; 338557; -.
DR GeneCards; FFAR4; -.
DR HGNC; HGNC:19061; FFAR4.
DR HPA; ENSG00000186188; Tissue enhanced (intestine, 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; ENSGT01020000230390; -.
DR HOGENOM; CLU_061487_0_0_1; -.
DR InParanoid; Q5NUL3; -.
DR OMA; TLPLCCF; -.
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; 16 hits in 1078 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 93 other tissues.
DR ExpressionAtlas; Q5NUL3; baseline and differential.
DR Genevisible; Q5NUL3; HS.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; 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: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 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; Cell projection; Differentiation;
KW Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein;
KW Inflammatory response; Lipid-binding; Lysosome; Membrane; Phosphoprotein;
KW 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 (associated with increased risk of 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 LCFA-
FT 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"
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
