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Protein

Free fatty acid receptor 2

Gene

Ffar2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine (PubMed:22190648, PubMed:23589301). May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake (PubMed:20399779). Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes (PubMed:16123168, PubMed:23589301). In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines (PubMed:23665276). May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils (PubMed:19917676, PubMed:19865172). In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes.9 Publications

GO - Molecular functioni

  • G-protein coupled receptor activity Source: UniProtKB
  • lipid binding Source: UniProtKB-KW

GO - Biological processi

  • cell surface pattern recognition receptor signaling pathway Source: UniProtKB
  • cellular response to fatty acid Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • leukocyte chemotaxis involved in inflammatory response Source: UniProtKB
  • lipid storage Source: UniProtKB
  • mucosal immune response Source: UniProtKB
  • positive regulation of acute inflammatory response to non-antigenic stimulus Source: UniProtKB
  • positive regulation of chemokine production Source: UniProtKB
  • positive regulation of cytokine production involved in immune response Source: UniProtKB
  • positive regulation of interleukin-8 secretion Source: UniProtKB
  • regulation of acute inflammatory response Source: UniProtKB
  • regulation of peptide hormone secretion Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Immunity, Inflammatory response

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-416476. G alpha (q) signalling events.
R-MMU-444209. Free fatty acid receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Free fatty acid receptor 2
Alternative name(s):
G-protein coupled receptor 43
Leukocyte-specific STAT-induced GPCR
Gene namesi
Name:Ffar2
Synonyms:Gpr43, Lssig
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2441731. Ffar2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88ExtracellularSequence analysis
Transmembranei9 – 2921Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini30 – 4314CytoplasmicSequence analysisAdd
BLAST
Transmembranei44 – 6421Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini65 – 7915ExtracellularSequence analysisAdd
BLAST
Transmembranei80 – 10021Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini101 – 12626CytoplasmicSequence analysisAdd
BLAST
Transmembranei127 – 14721Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini148 – 18437ExtracellularSequence analysisAdd
BLAST
Transmembranei185 – 20521Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini206 – 21914CytoplasmicSequence analysisAdd
BLAST
Transmembranei220 – 24021Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini241 – 25515ExtracellularSequence analysisAdd
BLAST
Transmembranei256 – 27621Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini277 – 33054CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Knockout mice display altered protective intestinal inflammatory and immune responses but no gross developmental defects.3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi159 – 1591E → G: Gain of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication

Chemistry

ChEMBLiCHEMBL3309047.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 330330Free fatty acid receptor 2PRO_0000228144Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi151 – 1511N-linked (GlcNAc...)Sequence analysis
Glycosylationi167 – 1671N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8VCK6.
PRIDEiQ8VCK6.

PTM databases

iPTMnetiQ8VCK6.
PhosphoSiteiQ8VCK6.

Expressioni

Tissue specificityi

Highly expressed in hematopoietic tissues, such as spleen and bone marrow, with highest levels in a subset of immune cells, including monocytes or neutrophils. Expressed in adipose tissues with high expression in differentiating adipocytes. Expressed by intestinal endocrine cells.3 Publications

Inductioni

During differentiation of leukocytes. This induction is STAT3-dependent. Up-regulated in adipose tissues by high-fat diet.2 Publications

Gene expression databases

BgeeiQ8VCK6.
CleanExiMM_FFAR2.
ExpressionAtlasiQ8VCK6. baseline and differential.
GenevisibleiQ8VCK6. MM.

Interactioni

Subunit structurei

Interacts with FCN1 (via Fibrinogen C-terminal domain).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000052600.

Structurei

3D structure databases

ProteinModelPortaliQ8VCK6.
SMRiQ8VCK6. Positions 14-290.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi216 – 2194Poly-Arg

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IITC. Eukaryota.
ENOG4111Q82. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000026778.
HOVERGENiHBG051811.
InParanoidiQ8VCK6.
KOiK04328.
OMAiGHCTIVI.
OrthoDBiEOG7SFHXH.
PhylomeDBiQ8VCK6.
TreeFamiTF350010.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VCK6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPDWHSSLI LTAYILIFLT GLPANLLALR AFMGRVRQPQ PAPVHILLLN
60 70 80 90 100
LTLADLLLLL LLPFRIVEAA SNFRWYLPKI VCALTGFGFY SSIYCSTWLL
110 120 130 140 150
AGISMERYLG VAFPVQYKLS RRPLYGVIAA LVAWIMSFGH CTIVIIVQYL
160 170 180 190 200
NSTEQVGTEN QITCYENFTQ EQLDVVLPVR LELCLVLFFV PMAVTIFCYW
210 220 230 240 250
RFVWIMLTQP HVGAQRRRRA VGLAVVTLLN FLVCFGPYNM SHLVGFYLRQ
260 270 280 290 300
SPSWRVEAVV FSSLNASLDP LLFYFSSSVV RRAFGKGLLL IRNPASSMLG
310 320 330
RGAKETVEGT KMDRGGSQAE GVQSSEFVTE
Length:330
Mass (Da):37,124
Last modified:March 1, 2002 - v1
Checksum:i7AB16802561B8B46
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF545043 mRNA. Translation: AAO16236.1.
AK078861 mRNA. Translation: BAC37425.1.
BC019570 mRNA. Translation: AAH19570.1.
CCDSiCCDS21111.1.
RefSeqiNP_001161981.1. NM_001168509.1.
NP_001161982.1. NM_001168510.1.
NP_001161983.1. NM_001168511.1.
NP_001161984.1. NM_001168512.1.
NP_666299.1. NM_146187.4.
XP_011248850.1. XM_011250548.1.
XP_011248851.1. XM_011250549.1.
XP_011248852.1. XM_011250550.1.
XP_011248853.1. XM_011250551.1.
XP_011248854.1. XM_011250552.1.
XP_011248855.1. XM_011250553.1.
XP_011248856.1. XM_011250554.1.
UniGeneiMm.97338.

Genome annotation databases

EnsembliENSMUST00000053156; ENSMUSP00000052600; ENSMUSG00000051314.
ENSMUST00000163504; ENSMUSP00000127758; ENSMUSG00000051314.
ENSMUST00000168528; ENSMUSP00000129398; ENSMUSG00000051314.
GeneIDi233079.
KEGGimmu:233079.
UCSCiuc009ggn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF545043 mRNA. Translation: AAO16236.1.
AK078861 mRNA. Translation: BAC37425.1.
BC019570 mRNA. Translation: AAH19570.1.
CCDSiCCDS21111.1.
RefSeqiNP_001161981.1. NM_001168509.1.
NP_001161982.1. NM_001168510.1.
NP_001161983.1. NM_001168511.1.
NP_001161984.1. NM_001168512.1.
NP_666299.1. NM_146187.4.
XP_011248850.1. XM_011250548.1.
XP_011248851.1. XM_011250549.1.
XP_011248852.1. XM_011250550.1.
XP_011248853.1. XM_011250551.1.
XP_011248854.1. XM_011250552.1.
XP_011248855.1. XM_011250553.1.
XP_011248856.1. XM_011250554.1.
UniGeneiMm.97338.

3D structure databases

ProteinModelPortaliQ8VCK6.
SMRiQ8VCK6. Positions 14-290.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000052600.

Chemistry

ChEMBLiCHEMBL3309047.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ8VCK6.
PhosphoSiteiQ8VCK6.

Proteomic databases

PaxDbiQ8VCK6.
PRIDEiQ8VCK6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053156; ENSMUSP00000052600; ENSMUSG00000051314.
ENSMUST00000163504; ENSMUSP00000127758; ENSMUSG00000051314.
ENSMUST00000168528; ENSMUSP00000129398; ENSMUSG00000051314.
GeneIDi233079.
KEGGimmu:233079.
UCSCiuc009ggn.1. mouse.

Organism-specific databases

CTDi2867.
MGIiMGI:2441731. Ffar2.

Phylogenomic databases

eggNOGiENOG410IITC. Eukaryota.
ENOG4111Q82. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000026778.
HOVERGENiHBG051811.
InParanoidiQ8VCK6.
KOiK04328.
OMAiGHCTIVI.
OrthoDBiEOG7SFHXH.
PhylomeDBiQ8VCK6.
TreeFamiTF350010.

Enzyme and pathway databases

ReactomeiR-MMU-416476. G alpha (q) signalling events.
R-MMU-444209. Free fatty acid receptors.

Miscellaneous databases

PROiQ8VCK6.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VCK6.
CleanExiMM_FFAR2.
ExpressionAtlasiQ8VCK6. baseline and differential.
GenevisibleiQ8VCK6. MM.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3."
    Senga T., Iwamoto S., Yoshida T., Yokota T., Adachi K., Azuma E., Hamaguchi M., Iwamoto T.
    Blood 101:1185-1187(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
    Strain: ddY.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Colon.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Colon.
  4. "Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids."
    Nilsson N.E., Kotarsky K., Owman C., Olde B.
    Biochem. Biophys. Res. Commun. 303:1047-1052(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
  6. "Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids."
    Ge H., Li X., Weiszmann J., Wang P., Baribault H., Chen J.L., Tian H., Li Y.
    Endocrinology 149:4519-4526(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. Cited for: FUNCTION.
  8. "Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43."
    Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D., Schilter H.C., Rolph M.S., Mackay F., Artis D., Xavier R.J., Teixeira M.M., Mackay C.R.
    Nature 461:1282-1286(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  9. "Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids."
    Zaibi M.S., Stocker C.J., O'Dowd J., Davies A., Bellahcene M., Cawthorne M.A., Brown A.J., Smith D.M., Arch J.R.
    FEBS Lett. 584:2381-2386(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2."
    Tolhurst G., Heffron H., Lam Y.S., Parker H.E., Habib A.M., Diakogiannaki E., Cameron J., Grosse J., Reimann F., Gribble F.M.
    Diabetes 61:364-371(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  11. "Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3."
    Hudson B.D., Tikhonova I.G., Pandey S.K., Ulven T., Milligan G.
    J. Biol. Chem. 287:41195-41209(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-159.
  12. "Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice."
    Kim M.H., Kang S.G., Park J.H., Yanagisawa M., Kim C.H.
    Gastroenterology 145:396-406(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  13. "Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor."
    Hudson B.D., Due-Hansen M.E., Christiansen E., Hansen A.M., Mackenzie A.E., Murdoch H., Pandey S.K., Ward R.J., Marquez R., Tikhonova I.G., Ulven T., Milligan G.
    J. Biol. Chem. 288:17296-17312(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiFFAR2_MOUSE
AccessioniPrimary (citable) accession number: Q8VCK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2002
Last modified: June 8, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.