FFAR1_RAT
ID FFAR1_RAT Reviewed; 300 AA.
AC Q8K3T4;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Free fatty acid receptor 1;
DE AltName: Full=G-protein coupled receptor 40;
GN Name=Ffar1; Synonyms=Gpr40;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=12496284; DOI=10.1074/jbc.m211495200;
RA Briscoe C.P., Tadayyon M., Andrews J.L., Benson W.G., Chambers J.K.,
RA Eilert M.M., Ellis C., Elshourbagy N.A., Goetz A.S., Minnick D.T.,
RA Murdock P.R., Sauls H.R. Jr., Shabon U., Spinage L.D., Strum J.C.,
RA Szekeres P.G., Tan K.B., Way J.M., Ignar D.M., Wilson S., Muir A.I.;
RT "The orphan G protein-coupled receptor GPR40 is activated by medium and
RT long-chain fatty acids.";
RL J. Biol. Chem. 278:11303-11311(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12629551; DOI=10.1038/nature01478;
RA Itoh Y., Kawamata Y., Harada M., Kobayashi M., Fujii R., Fukusumi S.,
RA Ogi K., Hosoya M., Tanaka Y., Uejima H., Tanaka H., Maruyama M., Satoh R.,
RA Okubo S., Kizawa H., Komatsu H., Matsumura F., Noguchi Y., Shinohara T.,
RA Hinuma S., Fujisawa Y., Fujino M.;
RT "Free fatty acids regulate insulin secretion from pancreatic beta cells
RT through GPR40.";
RL Nature 422:173-176(2003).
CC -!- FUNCTION: G-protein coupled receptor for medium and long chain
CC saturated and unsaturated fatty acids that plays an important role in
CC glucose homeostasis. Fatty acid binding increases glucose-stimulated
CC insulin secretion, and may also enhance the secretion of glucagon-like
CC peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor
CC signaling activates pathways that inhibit osteoclast differentiation.
CC Ligand binding leads to a conformation change that triggers signaling
CC via G-proteins that activate phospholipase C, leading to an increase of
CC the intracellular calcium concentration. Seems to act through a G(q)
CC and G(i)-mediated pathway. Mediates the anti-inflammatory effects of
CC omega-3 polyunsaturated fatty acids (PUFAs) via inhibition of NLRP3
CC inflammasome activation. {ECO:0000250|UniProtKB:O14842,
CC ECO:0000250|UniProtKB:Q76JU9}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14842};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:O14842}.
CC -!- TISSUE SPECIFICITY: Expressed abundantly in pancreatic beta cells.
CC {ECO:0000269|PubMed:12496284, ECO:0000269|PubMed:12629551}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF539810; AAN03479.1; -; mRNA.
DR EMBL; AB095744; BAC82554.1; -; mRNA.
DR RefSeq; NP_695216.1; NM_153304.2.
DR AlphaFoldDB; Q8K3T4; -.
DR SMR; Q8K3T4; -.
DR STRING; 10116.ENSRNOP00000028533; -.
DR BindingDB; Q8K3T4; -.
DR ChEMBL; CHEMBL1795180; -.
DR GlyGen; Q8K3T4; 1 site.
DR PhosphoSitePlus; Q8K3T4; -.
DR PaxDb; Q8K3T4; -.
DR ABCD; Q8K3T4; 6 sequenced antibodies.
DR GeneID; 266607; -.
DR KEGG; rno:266607; -.
DR CTD; 2864; -.
DR RGD; 628613; Ffar1.
DR eggNOG; ENOG502QVCS; Eukaryota.
DR InParanoid; Q8K3T4; -.
DR OrthoDB; 1074213at2759; -.
DR PhylomeDB; Q8K3T4; -.
DR Reactome; R-RNO-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-RNO-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-434316; Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion.
DR Reactome; R-RNO-444209; Free fatty acid receptors.
DR PRO; PR:Q8K3T4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0045125; F:bioactive lipid receptor activity; ISS:UniProtKB.
DR GO; GO:0005504; F:fatty acid binding; IDA:RGD.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:UniProtKB.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR013312; GPR40-rel_orph.
DR InterPro; IPR013313; GPR40_recept_FA.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01905; FATTYACIDR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01904; GPR40FAMILY.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipid-binding; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..300
FT /note="Free fatty acid receptor 1"
FT /id="PRO_0000227756"
FT TOPO_DOM 1..8
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 9..31
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 32..41
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 42..64
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 65..79
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 80..101
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 102..121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 143..178
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 179..200
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 201..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 224..248
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 249..256
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TRANSMEM 257..279
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT TOPO_DOM 280..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14842, ECO:0000255"
FT SITE 145
FT /note="Important for receptor activation"
FT /evidence="ECO:0000250|UniProtKB:O14842"
FT SITE 172
FT /note="Important for receptor activation"
FT /evidence="ECO:0000250|UniProtKB:O14842"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 79..170
FT /evidence="ECO:0000250|UniProtKB:O14842"
SQ SEQUENCE 300 AA; 31836 MW; 4E882AB259A5DD4F CRC64;
MDLPPQLSFA LYVSAFALGF PLNLLAIRGA VSHAKLRLTP SLVYTLHLAC SDLLLAITLP
LKAVEALASG VWPLPLPFCP VFALAHFAPL YAGGGFLAAL SAGRYLGAAF PFGYQAIRRP
CYSWGVCVAI WALVLCHLGL ALGLEAPRGW VDNTTSSLGI NIPVNGSPVC LEAWDPDSAR
PARLSFSILL FFLPLVITAF CYVGCLRALV HSGLSHKRKL RAAWVAGGAL LTLLLCLGPY
NASNVASFIN PDLEGSWRKL GLITGAWSVV LNPLVTGYLG TGPGQGTICV TRTPRGTIQK
