FFAR2_RAT
ID FFAR2_RAT Reviewed; 330 AA.
AC Q76EI6;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Free fatty acid receptor 2;
DE AltName: Full=G-protein coupled receptor 43;
GN Name=Ffar2; Synonyms=Gpr43;
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tanaka H., Shinohara T., Ogi K., Hosoya M., Fukusumi S., Noguchi Y.,
RA Tanaka Y., Kizawa H., Fujii R., Itoh Y., Hinuma S., Fujisawa F., Fujino M.;
RT "Search for ligands of GPR43 and analysis for its mRNA expression.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=16453106; DOI=10.1007/s00441-005-0140-x;
RA Karaki S., Mitsui R., Hayashi H., Kato I., Sugiya H., Iwanaga T.,
RA Furness J.B., Kuwahara A.;
RT "Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine
RT cells and mucosal mast cells in rat intestine.";
RL Cell Tissue Res. 324:353-360(2006).
RN [3]
RP FUNCTION.
RX PubMed=23589301; DOI=10.1074/jbc.m113.455337;
RA Hudson B.D., Due-Hansen M.E., Christiansen E., Hansen A.M., Mackenzie A.E.,
RA Murdoch H., Pandey S.K., Ward R.J., Marquez R., Tikhonova I.G., Ulven T.,
RA Milligan G.;
RT "Defining the molecular basis for the first potent and selective
RT orthosteric agonists of the FFA2 free fatty acid receptor.";
RL J. Biol. Chem. 288:17296-17312(2013).
CC -!- FUNCTION: G protein-coupled receptor that is activated by a major
CC product of dietary fiber digestion, the short chain fatty acids
CC (SCFAs), and that plays a role in the regulation of whole-body energy
CC homeostasis and in intestinal immunity. In omnivorous mammals, the
CC short chain fatty acids acetate, propionate and butyrate are produced
CC primarily by the gut microbiome that metabolizes dietary fibers. SCFAs
CC serve as a source of energy but also act as signaling molecules. That G
CC protein-coupled receptor is probably coupled to the pertussis toxin-
CC sensitive, G(i/o)-alpha family of G proteins but also to the Gq family
CC (PubMed:23589301). Its activation results in the formation of inositol
CC 1,4,5-trisphosphate, the mobilization of intracellular calcium, the
CC phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the
CC inhibition of intracellular cAMP accumulation. May play a role in
CC glucose homeostasis by regulating the secretion of GLP-1, in response
CC to short-chain fatty acids accumulating in the intestine. May also
CC regulate the production of LEP/Leptin, a hormone acting on the central
CC nervous system to inhibit food intake. Finally, may also regulate
CC whole-body energy homeostasis through adipogenesis regulating both
CC differentiation and lipid storage of adipocytes. In parallel to its
CC role in energy homeostasis, may also mediate the activation of the
CC inflammatory and immune responses by SCFA in the intestine, regulating
CC the rapid production of chemokines and cytokines. May also play a role
CC in the resolution of the inflammatory response and control chemotaxis
CC in neutrophils. In addition to SCFAs, may also be activated by the
CC extracellular lectin FCN1 in a process leading to activation of
CC monocytes and inducing the secretion of interleukin-8/IL-8 in response
CC to the presence of microbes. {ECO:0000269|PubMed:23589301}.
CC -!- SUBUNIT: Interacts with FCN1 (via Fibrinogen C-terminal domain).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in whole wall and separated mucosa in the
CC distal ileum and colon. Expressed by enteroendocrine cells expressing
CC peptide YY (PYY) (at protein level). {ECO:0000269|PubMed:16453106}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB106675; BAD02826.1; -; mRNA.
DR RefSeq; NP_001005877.1; NM_001005877.1.
DR RefSeq; XP_006228884.1; XM_006228822.3.
DR RefSeq; XP_008757355.1; XM_008759133.2.
DR RefSeq; XP_008757356.1; XM_008759134.2.
DR RefSeq; XP_008757357.1; XM_008759135.1.
DR RefSeq; XP_017444402.1; XM_017588913.1.
DR AlphaFoldDB; Q76EI6; -.
DR SMR; Q76EI6; -.
DR STRING; 10116.ENSRNOP00000028532; -.
DR BindingDB; Q76EI6; -.
DR ChEMBL; CHEMBL3309100; -.
DR GuidetoPHARMACOLOGY; 226; -.
DR GlyGen; Q76EI6; 2 sites.
DR PhosphoSitePlus; Q76EI6; -.
DR PaxDb; Q76EI6; -.
DR Ensembl; ENSRNOT00000028532; ENSRNOP00000028532; ENSRNOG00000021021.
DR Ensembl; ENSRNOT00000110584; ENSRNOP00000092741; ENSRNOG00000021021.
DR Ensembl; ENSRNOT00000111135; ENSRNOP00000076649; ENSRNOG00000021021.
DR GeneID; 292794; -.
DR KEGG; rno:292794; -.
DR UCSC; RGD:1359614; rat.
DR CTD; 2867; -.
DR RGD; 1359614; Ffar2.
DR eggNOG; ENOG502QQGM; Eukaryota.
DR GeneTree; ENSGT00990000203527; -.
DR HOGENOM; CLU_009579_8_4_1; -.
DR InParanoid; Q76EI6; -.
DR OMA; ITIFCYW; -.
DR OrthoDB; 1129026at2759; -.
DR PhylomeDB; Q76EI6; -.
DR TreeFam; TF350010; -.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-444209; Free fatty acid receptors.
DR PRO; PR:Q76EI6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021021; Expressed in colon and 10 other tissues.
DR Genevisible; Q76EI6; RN.
DR GO; GO:0042995; C:cell projection; IDA:RGD.
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:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0002752; P:cell surface pattern recognition receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; ISS:UniProtKB.
DR GO; GO:0002385; P:mucosal immune response; ISS:UniProtKB.
DR GO; GO:0002879; P:positive regulation of acute inflammatory response to non-antigenic stimulus; ISS:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0002673; P:regulation of acute inflammatory response; ISS:UniProtKB.
DR GO; GO:0090276; P:regulation of peptide hormone secretion; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR013312; GPR40-rel_orph.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01904; GPR40FAMILY.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; G-protein coupled receptor; Glycoprotein; Immunity;
KW Inflammatory response; Lipid-binding; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..330
FT /note="Free fatty acid receptor 2"
FT /id="PRO_0000228145"
FT TOPO_DOM 1..8
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..64
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..79
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 148..184
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 241..255
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 300..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 330 AA; 36994 MW; CF32C5B5D226670B CRC64;
MTPDWHSSLI LTAYILIFLT GLPANLLALR AFVSRVRQPQ PAPVHILLLN LTLADLLLLL
LLPFRIVEAA SNFRWYLPKI VCALTGFGFY SSIYCSTWLL AGISIERYLG VAFPVQYKLS
RRPLYGVIAA LVAWIMSFGH CTIVIIVQYL NSTEQVGTEN QITCYENFTQ AQLDVVLPVR
LELCLVLFFV PMTVTIFCYW RFVWIMLTQP HVGAQRRRRA VGLAVVTLLN FLVCFGPYNM
SHLVGFHLRQ SPSWRVEAVV FSSLNASLDP LLFYFSSSVV RRAFGKGLLL LRNPGSSMLG
RGAEETVEGT KTDRGGSQTE GAQSSDFVTE
