FFAR3_RAT
ID FFAR3_RAT Reviewed; 319 AA.
AC B2GV46;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Free fatty acid receptor 3;
DE AltName: Full=G-protein coupled receptor 41;
GN Name=Ffar3; Synonyms=Gpr41;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [4]
RP FUNCTION, AND MUTAGENESIS OF ARG-40; ARG-41; ARG-170; LEU-223 AND THR-252.
RX PubMed=12496283; DOI=10.1074/jbc.m211609200;
RA Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M.M., Tcheang L.,
RA Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J.,
RA Pike N.B., Strum J.C., Steplewski K.M., Murdock P.R., Holder J.C.,
RA Marshall F.H., Szekeres P.G., Wilson S., Ignar D.M., Foord S.M., Wise A.,
RA Dowell S.J.;
RT "The orphan G protein-coupled receptors GPR41 and GPR43 are activated by
RT propionate and other short chain carboxylic acids.";
RL J. Biol. Chem. 278:11312-11319(2003).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24305827; DOI=10.1523/jneurosci.3102-13.2013;
RA Won Y.J., Lu V.B., Puhl H.L. III, Ikeda S.R.;
RT "beta-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic
RT neurons by acting as an agonist for the G-protein-coupled receptor FFA3.";
RL J. Neurosci. 33:19314-19325(2013).
RN [6]
RP FUNCTION.
RX PubMed=24412651; DOI=10.1016/j.cell.2013.12.016;
RA De Vadder F., Kovatcheva-Datchary P., Goncalves D., Vinera J., Zitoun C.,
RA Duchampt A., Baeckhed F., Mithieux G.;
RT "Microbiota-generated metabolites promote metabolic benefits via gut-brain
RT neural circuits.";
RL Cell 156:84-96(2014).
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. Its activation results in
CC the formation of inositol 1,4,5-trisphosphate, the mobilization of
CC intracellular calcium, the phosphorylation of the MAPK3/ERK1 and
CC MAPK1/ERK2 kinases and the inhibition of intracellular cAMP
CC accumulation. Activated by SCFAs and by beta-hydroxybutyrate, a ketone
CC body produced by the liver upon starvation, it inhibits N-type calcium
CC channels and modulates the activity of sympathetic neurons through a
CC signaling cascade involving the beta and gamma subunits of its coupled
CC G protein, phospholipase C and MAP kinases (PubMed:24305827). Thereby,
CC it may regulate energy expenditure through the control of the
CC sympathetic nervous system that controls for instance heart rate. Upon
CC activation by SCFAs accumulating in the intestine, it may also signal
CC to the brain via neural circuits which in turn would regulate
CC intestinal gluconeogenesis (PubMed:24412651). May also control the
CC production of hormones involved in whole-body energy homeostasis. May
CC for instance, regulate blood pressure through renin secretion. May also
CC regulate secretion of the PYY peptide by enteroendocrine cells and
CC control gut motility, intestinal transit rate, and the harvesting of
CC energy from SCFAs produced by gut microbiota. May also indirectly
CC regulate the production of LEP/Leptin, a hormone acting on the CNS to
CC inhibit food intake, in response to the presence of short-chain fatty
CC acids in the intestine. Finally, may also play a role in glucose
CC homeostasis. Besides its role in energy homeostasis, may play a role in
CC intestinal immunity. May mediate the activation of the inflammatory and
CC immune response by SCFAs in the gut, regulating the rapid production of
CC chemokines and cytokines by intestinal epithelial cells.
CC {ECO:0000269|PubMed:12496283, ECO:0000269|PubMed:24305827,
CC ECO:0000269|PubMed:24412651}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the sympathetic nervous system.
CC {ECO:0000269|PubMed:24305827}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AABR06004309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473979; EDM07705.1; -; Genomic_DNA.
DR EMBL; BC166522; AAI66522.1; -; mRNA.
DR RefSeq; NP_001102382.1; NM_001108912.1.
DR AlphaFoldDB; B2GV46; -.
DR SMR; B2GV46; -.
DR STRING; 10116.ENSRNOP00000053557; -.
DR BindingDB; B2GV46; -.
DR ChEMBL; CHEMBL3886125; -.
DR PaxDb; B2GV46; -.
DR Ensembl; ENSRNOT00000056714; ENSRNOP00000053557; ENSRNOG00000037467.
DR GeneID; 365228; -.
DR KEGG; rno:365228; -.
DR UCSC; RGD:1311035; rat.
DR CTD; 2865; -.
DR RGD; 1311035; Ffar3.
DR eggNOG; ENOG502QQGM; Eukaryota.
DR GeneTree; ENSGT00990000203527; -.
DR HOGENOM; CLU_009579_8_4_1; -.
DR InParanoid; B2GV46; -.
DR OMA; HWLYFSV; -.
DR OrthoDB; 1129026at2759; -.
DR PhylomeDB; B2GV46; -.
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:B2GV46; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000037467; Expressed in jejunum and 4 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
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:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0002385; P:mucosal immune response; ISS:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl.
DR GO; GO:0045760; P:positive regulation of action potential; ISO:RGD.
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:1904457; P:positive regulation of neuronal action potential; IEA:Ensembl.
DR GO; GO:0003062; P:regulation of heart rate by chemical signal; ISO:RGD.
DR GO; GO:0046885; P:regulation of hormone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; 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; Disulfide bond; G-protein coupled receptor; Immunity;
KW Inflammatory response; Lipid-binding; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..319
FT /note="Free fatty acid receptor 3"
FT /id="PRO_0000430312"
FT TOPO_DOM 1..15
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..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..98
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..127
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..148
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..206
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..254
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 276..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DISULFID 84..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 40
FT /note="R->Q: No effect on activation by propionate."
FT /evidence="ECO:0000269|PubMed:12496283"
FT MUTAGEN 41
FT /note="R->C: No effect on activation by propionate."
FT /evidence="ECO:0000269|PubMed:12496283"
FT MUTAGEN 170
FT /note="R->W: Loss of activation by propionate."
FT /evidence="ECO:0000269|PubMed:12496283"
FT MUTAGEN 223
FT /note="L->V: Constitutively active."
FT /evidence="ECO:0000269|PubMed:12496283"
FT MUTAGEN 252
FT /note="T->V: Reduced activation by propionate."
FT /evidence="ECO:0000269|PubMed:12496283"
SQ SEQUENCE 319 AA; 36483 MW; 076C42FB2383161A CRC64;
MDTSFFPGNH WLFFSVDLLV FLVGLPLNVM ALVVFVNKLR RRPVAVDLLL LNLTISDLLL
LLFLPFRIVE AACGMKWILP FIFCPLSGFL FFTTIYLTSL FLMTVSIERF LSVAYPLWYK
TRPRLAQAGL VSGICWFLAS AHCSVIYVTE YWGNATYSQG TNGTCYLEFR EDQLAILLPV
RLEMAVVLFM VPLCITSYCY SRLVWILSQG ASRRRRKRVM GLLVATLLIF FVCFGPYNMS
HVVGYVRGES PTWRSYVLLL STLNSCIDPL VFYFSSSKFQ ADFHQLLSRL IRACVPWTQE
VSLELKVKNG EEPSKECPS
