FFAR2_MOUSE
ID FFAR2_MOUSE Reviewed; 330 AA.
AC Q8VCK6;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Free fatty acid receptor 2;
DE AltName: Full=G-protein coupled receptor 43;
DE AltName: Full=Leukocyte-specific STAT-induced GPCR;
GN Name=Ffar2; Synonyms=Gpr43, Lssig;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=ddY;
RX PubMed=12393494; DOI=10.1182/blood-2002-06-1881;
RA Senga T., Iwamoto S., Yoshida T., Yokota T., Adachi K., Azuma E.,
RA Hamaguchi M., Iwamoto T.;
RT "LSSIG is a novel murine leukocyte-specific GPCR that is induced by the
RT activation of STAT3.";
RL Blood 101:1185-1187(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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.
RX PubMed=12684041; DOI=10.1016/s0006-291x(03)00488-1;
RA Nilsson N.E., Kotarsky K., Owman C., Olde B.;
RT "Identification of a free fatty acid receptor, FFA2R, expressed on
RT leukocytes and activated by short-chain fatty acids.";
RL Biochem. Biophys. Res. Commun. 303:1047-1052(2003).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16123168; DOI=10.1210/en.2005-0545;
RA Hong Y.H., Nishimura Y., Hishikawa D., Tsuzuki H., Miyahara H., Gotoh C.,
RA Choi K.C., Feng D.D., Chen C., Lee H.G., Katoh K., Roh S.G., Sasaki S.;
RT "Acetate and propionate short chain fatty acids stimulate adipogenesis via
RT GPCR43.";
RL Endocrinology 146:5092-5099(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18499755; DOI=10.1210/en.2008-0059;
RA Ge H., Li X., Weiszmann J., Wang P., Baribault H., Chen J.L., Tian H.,
RA Li Y.;
RT "Activation of G protein-coupled receptor 43 in adipocytes leads to
RT inhibition of lipolysis and suppression of plasma free fatty acids.";
RL Endocrinology 149:4519-4526(2008).
RN [7]
RP FUNCTION.
RX PubMed=19917676; DOI=10.4049/jimmunol.0900063;
RA Sina C., Gavrilova O., Forster M., Till A., Derer S., Hildebrand F.,
RA Raabe B., Chalaris A., Scheller J., Rehmann A., Franke A., Ott S.,
RA Hasler R., Nikolaus S., Folsch U.R., Rose-John S., Jiang H.P., Li J.,
RA Schreiber S., Rosenstiel P.;
RT "G protein-coupled receptor 43 is essential for neutrophil recruitment
RT during intestinal inflammation.";
RL J. Immunol. 183:7514-7522(2009).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19865172; DOI=10.1038/nature08530;
RA Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D.,
RA Schilter H.C., Rolph M.S., Mackay F., Artis D., Xavier R.J., Teixeira M.M.,
RA Mackay C.R.;
RT "Regulation of inflammatory responses by gut microbiota and chemoattractant
RT receptor GPR43.";
RL Nature 461:1282-1286(2009).
RN [9]
RP FUNCTION.
RX PubMed=20399779; DOI=10.1016/j.febslet.2010.04.027;
RA Zaibi M.S., Stocker C.J., O'Dowd J., Davies A., Bellahcene M.,
RA Cawthorne M.A., Brown A.J., Smith D.M., Arch J.R.;
RT "Roles of GPR41 and GPR43 in leptin secretory responses of murine
RT adipocytes to short chain fatty acids.";
RL FEBS Lett. 584:2381-2386(2010).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22190648; DOI=10.2337/db11-1019;
RA Tolhurst G., Heffron H., Lam Y.S., Parker H.E., Habib A.M.,
RA Diakogiannaki E., Cameron J., Grosse J., Reimann F., Gribble F.M.;
RT "Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via
RT the G-protein-coupled receptor FFAR2.";
RL Diabetes 61:364-371(2012).
RN [11]
RP MUTAGENESIS OF GLU-159.
RX PubMed=23066016; DOI=10.1074/jbc.m112.396259;
RA Hudson B.D., Tikhonova I.G., Pandey S.K., Ulven T., Milligan G.;
RT "Extracellular ionic locks determine variation in constitutive activity and
RT ligand potency between species orthologs of the free fatty acid receptors
RT FFA2 and FFA3.";
RL J. Biol. Chem. 287:41195-41209(2012).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23665276; DOI=10.1053/j.gastro.2013.04.056;
RA Kim M.H., Kang S.G., Park J.H., Yanagisawa M., Kim C.H.;
RT "Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial
RT cells to promote inflammatory responses in mice.";
RL Gastroenterology 145:396-406(2013).
RN [13]
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
CC (PubMed:22190648, PubMed:23589301). May also regulate the production of
CC LEP/Leptin, a hormone acting on the central nervous system to inhibit
CC food intake (PubMed:20399779). Finally, may also regulate whole-body
CC energy homeostasis through adipogenesis regulating both differentiation
CC and lipid storage of adipocytes (PubMed:16123168, PubMed:23589301). In
CC parallel to its role in energy homeostasis, may also mediate the
CC activation of the inflammatory and immune responses by SCFA in the
CC intestine, regulating the rapid production of chemokines and cytokines
CC (PubMed:23665276). May also play a role in the resolution of the
CC inflammatory response and control chemotaxis in neutrophils
CC (PubMed:19917676, PubMed:19865172). In addition to SCFAs, may also be
CC activated by the extracellular lectin FCN1 in a process leading to
CC activation of monocytes and inducing the secretion of interleukin-8/IL-
CC 8 in response to the presence of microbes.
CC {ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:16123168,
CC ECO:0000269|PubMed:18499755, ECO:0000269|PubMed:19865172,
CC ECO:0000269|PubMed:19917676, ECO:0000269|PubMed:20399779,
CC ECO:0000269|PubMed:22190648, ECO:0000269|PubMed:23589301,
CC ECO:0000269|PubMed:23665276}.
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: Highly expressed in hematopoietic tissues, such as
CC spleen and bone marrow, with highest levels in a subset of immune
CC cells, including monocytes or neutrophils. Expressed in adipose tissues
CC with high expression in differentiating adipocytes. Expressed by
CC intestinal endocrine cells. {ECO:0000269|PubMed:12393494,
CC ECO:0000269|PubMed:16123168, ECO:0000269|PubMed:22190648}.
CC -!- INDUCTION: During differentiation of leukocytes. This induction is
CC STAT3-dependent. Up-regulated in adipose tissues by high-fat diet.
CC {ECO:0000269|PubMed:12393494, ECO:0000269|PubMed:16123168}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice display altered protective
CC intestinal inflammatory and immune responses but no gross developmental
CC defects. {ECO:0000269|PubMed:18499755, ECO:0000269|PubMed:19865172,
CC ECO:0000269|PubMed:23665276}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF545043; AAO16236.1; -; mRNA.
DR EMBL; AK078861; BAC37425.1; -; mRNA.
DR EMBL; BC019570; AAH19570.1; -; mRNA.
DR CCDS; CCDS21111.1; -.
DR RefSeq; NP_001161981.1; NM_001168509.1.
DR RefSeq; NP_001161982.1; NM_001168510.1.
DR RefSeq; NP_001161983.1; NM_001168511.1.
DR RefSeq; NP_001161984.1; NM_001168512.1.
DR RefSeq; NP_666299.1; NM_146187.4.
DR RefSeq; XP_011248850.1; XM_011250548.2.
DR RefSeq; XP_011248851.1; XM_011250549.2.
DR RefSeq; XP_011248854.1; XM_011250552.2.
DR RefSeq; XP_011248855.1; XM_011250553.2.
DR RefSeq; XP_011248856.1; XM_011250554.2.
DR AlphaFoldDB; Q8VCK6; -.
DR SMR; Q8VCK6; -.
DR STRING; 10090.ENSMUSP00000052600; -.
DR BindingDB; Q8VCK6; -.
DR ChEMBL; CHEMBL3309047; -.
DR GuidetoPHARMACOLOGY; 226; -.
DR GlyGen; Q8VCK6; 2 sites.
DR iPTMnet; Q8VCK6; -.
DR PhosphoSitePlus; Q8VCK6; -.
DR PaxDb; Q8VCK6; -.
DR PRIDE; Q8VCK6; -.
DR ProteomicsDB; 271691; -.
DR Antibodypedia; 15916; 349 antibodies from 31 providers.
DR DNASU; 233079; -.
DR Ensembl; ENSMUST00000053156; ENSMUSP00000052600; ENSMUSG00000051314.
DR Ensembl; ENSMUST00000163504; ENSMUSP00000127758; ENSMUSG00000051314.
DR Ensembl; ENSMUST00000168528; ENSMUSP00000129398; ENSMUSG00000051314.
DR GeneID; 233079; -.
DR KEGG; mmu:233079; -.
DR UCSC; uc009ggn.1; mouse.
DR CTD; 2867; -.
DR MGI; MGI:2441731; Ffar2.
DR VEuPathDB; HostDB:ENSMUSG00000051314; -.
DR eggNOG; ENOG502QQGM; Eukaryota.
DR GeneTree; ENSGT00990000203527; -.
DR HOGENOM; CLU_009579_8_4_1; -.
DR InParanoid; Q8VCK6; -.
DR OMA; ITIFCYW; -.
DR OrthoDB; 1129026at2759; -.
DR PhylomeDB; Q8VCK6; -.
DR TreeFam; TF350010; -.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-444209; Free fatty acid receptors.
DR BioGRID-ORCS; 233079; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ffar2; mouse.
DR PRO; PR:Q8VCK6; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8VCK6; protein.
DR Bgee; ENSMUSG00000051314; Expressed in dorsal pancreas and 87 other tissues.
DR ExpressionAtlas; Q8VCK6; baseline and differential.
DR Genevisible; Q8VCK6; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IDA:UniProtKB.
DR GO; GO:0002385; P:mucosal immune response; IMP:UniProtKB.
DR GO; GO:0002879; P:positive regulation of acute inflammatory response to non-antigenic stimulus; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IMP:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0002673; P:regulation of acute inflammatory response; IMP:UniProtKB.
DR GO; GO:0090276; P:regulation of peptide hormone secretion; IDA: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_0000228144"
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 306..330
FT /note="Disordered"
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"
FT MUTAGEN 159
FT /note="E->G: Gain of SCFA-independent constitutive G
FT protein-coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:23066016"
SQ SEQUENCE 330 AA; 37124 MW; 7AB16802561B8B46 CRC64;
MTPDWHSSLI LTAYILIFLT GLPANLLALR AFMGRVRQPQ PAPVHILLLN LTLADLLLLL
LLPFRIVEAA SNFRWYLPKI VCALTGFGFY SSIYCSTWLL AGISMERYLG VAFPVQYKLS
RRPLYGVIAA LVAWIMSFGH CTIVIIVQYL NSTEQVGTEN QITCYENFTQ EQLDVVLPVR
LELCLVLFFV PMAVTIFCYW RFVWIMLTQP HVGAQRRRRA VGLAVVTLLN FLVCFGPYNM
SHLVGFYLRQ SPSWRVEAVV FSSLNASLDP LLFYFSSSVV RRAFGKGLLL IRNPASSMLG
RGAKETVEGT KMDRGGSQAE GVQSSEFVTE
