FFAR4_RAT
ID FFAR4_RAT Reviewed; 361 AA.
AC Q2AC31;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Free fatty acid receptor 4;
DE AltName: Full=G-protein coupled receptor 120;
DE AltName: Full=Omega-3 fatty acid receptor 1;
GN Name=Ffar4; Synonyms=Gpr120, O3far1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:BAE80312.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yano T., Katsuma S., Hirasawa A., Tsujimoto G.;
RT "Cloning and characterization of rat GPR120.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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. LCFAs sensing
CC initiates activation of phosphoinositidase C-linked G proteins GNAQ and
CC GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second
CC messenger pathways such as intracellular calcium mobilization,
CC modulation of cyclic adenosine monophosphate (cAMP) production, and
CC mitogen-activated protein kinases (MAPKs). After LCFAs binding,
CC associates with beta-arrestin ARRB2 that acts as an adapter protein
CC coupling the receptor to specific downstream signaling pathways, as
CC well as mediating receptor endocytosis (By similarity). In response to
CC dietary fats, plays an important role in the regulation of adipocyte
CC proliferation and differentiation. Acts as a receptor for omega-3
CC polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular
CC preadipocytes, initiating an adipogenic program via cAMP and CTCF-
CC dependent chromatin remodeling that ultimately results in
CC transcriptional activation of adipogenic genes and cell cycle entry.
CC Induces differentiation of brown and beige adipocytes probably via
CC autocrine and endocrine functions of FGF21 hormone. Contributes to the
CC thermogenic activation of brown adipose tissue and the browning of
CC white adipose tissue. Activates brown adipocytes by initiating
CC intracellular calcium signaling leading to mitochondrial depolarization
CC and fission, and overall increased mitochondrial respiration.
CC Consequently stimulates fatty acid uptake and oxidation in mitochondria
CC together with UCP1-mediated thermogenic respiration, eventually
CC reducing fat mass. Regulates bi-potential differentiation of bone
CC marrow mesenchymal stem cells toward osteoblasts or adipocytes likely
CC by up-regulating distinct integrins. In response to dietary fats
CC regulates hormone secretion and appetite. 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. Negatively regulates glucose-induced SST
CC secretion in pancreatic delta cells. Mediates LCFAs inhibition of GHRL
CC secretion, an appetite-controlling hormone. In taste buds, contributes
CC to sensing of dietary fatty acids by the gustatory system. 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 (By similarity). 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 (By similarity). Mediates LCFAs anti-apoptotic effects
CC (By similarity). {ECO:0000250|UniProtKB:Q5NUL3,
CC ECO:0000250|UniProtKB:Q7TMA4}.
CC -!- SUBUNIT: Interacts (via C-terminus) with ARRB2 following LCFAs
CC stimulation. {ECO:0000250|UniProtKB:Q5NUL3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q7TMA4};
CC Multi-pass 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:0000250|UniProtKB:Q7TMA4}; 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 (By similarity). {ECO:0000250|UniProtKB:Q5NUL3,
CC ECO:0000250|UniProtKB:Q7TMA4}.
CC -!- PTM: Phosphorylated at two clusters of Ser and Thr residues located in
CC the intracellular C-terminus. Prerequisite for FFAR4 internalization
CC via an ARRB2-dependent pathway. {ECO:0000250|UniProtKB:Q5NUL3}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB207868; BAE80312.1; -; mRNA.
DR RefSeq; NP_001040553.1; NM_001047088.1.
DR AlphaFoldDB; Q2AC31; -.
DR SMR; Q2AC31; -.
DR STRING; 10116.ENSRNOP00000032715; -.
DR BindingDB; Q2AC31; -.
DR ChEMBL; CHEMBL3309099; -.
DR GuidetoPHARMACOLOGY; 127; -.
DR GlyGen; Q2AC31; 1 site.
DR PhosphoSitePlus; Q2AC31; -.
DR PaxDb; Q2AC31; -.
DR Ensembl; ENSRNOT00000034563; ENSRNOP00000032715; ENSRNOG00000021763.
DR GeneID; 294075; -.
DR KEGG; rno:294075; -.
DR UCSC; RGD:1308252; rat.
DR CTD; 338557; -.
DR RGD; 1308252; Ffar4.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230390; -.
DR HOGENOM; CLU_061487_0_0_1; -.
DR InParanoid; Q2AC31; -.
DR OMA; TLPLCCF; -.
DR OrthoDB; 1057232at2759; -.
DR PhylomeDB; Q2AC31; -.
DR TreeFam; TF336844; -.
DR Reactome; R-RNO-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:Q2AC31; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021763; Expressed in colon and 9 other tissues.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; ISO:RGD.
DR GO; GO:0005504; F:fatty acid binding; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISO:RGD.
DR GO; GO:0008527; F:taste receptor activity; ISO:RGD.
DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:CACAO.
DR GO; GO:0036321; P:ghrelin secretion; ISS:UniProtKB.
DR GO; GO:0046879; P:hormone secretion; ISO:RGD.
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; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISO:RGD.
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; ISO:RGD.
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; 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 2: Evidence at transcript 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_0000262961"
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 REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 347
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5NUL3"
FT MOD_RES 349
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5NUL3"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5NUL3"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5NUL3"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5NUL3"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 111..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 361 AA; 40902 MW; 8444F22C1CB7DC0F CRC64;
MSPECAQTTG PGPSRTPDQV NRTHFPFFSD VKGDHRLVLS VLETTVLGLI FVVSLLGNVC
ALVLVVRRRR RGATVSLVLN LFCADLLFTS AIPLVLVVRW TEAWLLGPVV CHLLFYVMTM
SGSVTILTLA AVSLERMVCI VRLRRGLSGP GRRTQAALLA FIWGYSALAA LPLCILFRVV
PQRLPGGDQE IPICTLDWPN RIGEISWDVF FVTLNFLVPG LVIVISYSKI LQITKASRKR
LTLSLAYSES HQIRVSQQDY RLFRTLFLLM VSFFIMWSPI IITILLILIQ NFRQDLVIWP
SLFFWVVAFT FANSALNPIL YNMSLFRSEW RKIFCCFFFP EKGAIFTETS IRRNDLSVIS
T
