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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)DescriptionActionsGraphical viewLength
Topological domaini1 – 8ExtracellularSequence analysis8
Transmembranei9 – 29Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini30 – 43CytoplasmicSequence analysisAdd BLAST14
Transmembranei44 – 64Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini65 – 79ExtracellularSequence analysisAdd BLAST15
Transmembranei80 – 100Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini101 – 126CytoplasmicSequence analysisAdd BLAST26
Transmembranei127 – 147Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini148 – 184ExtracellularSequence analysisAdd BLAST37
Transmembranei185 – 205Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini206 – 219CytoplasmicSequence analysisAdd BLAST14
Transmembranei220 – 240Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini241 – 255ExtracellularSequence analysisAdd BLAST15
Transmembranei256 – 276Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini277 – 330CytoplasmicSequence analysisAdd BLAST54

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)DescriptionActionsGraphical viewLength
Mutagenesisi159E → G: Gain of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3309047.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002281441 – 330Free fatty acid receptor 2Add BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi151N-linked (GlcNAc...)Sequence analysis1
Glycosylationi167N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8VCK6.
PRIDEiQ8VCK6.

PTM databases

iPTMnetiQ8VCK6.
PhosphoSitePlusiQ8VCK6.

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

BgeeiENSMUSG00000051314.
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.

Chemistry databases

BindingDBiQ8VCK6.

Structurei

3D structure databases

ProteinModelPortaliQ8VCK6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi216 – 219Poly-Arg4

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.
OrthoDBiEOG091G0EX2.
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_011250548.2.
XP_011248851.1. XM_011250549.2.
XP_011248854.1. XM_011250552.2.
XP_011248855.1. XM_011250553.2.
XP_011248856.1. XM_011250554.2.
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_011250548.2.
XP_011248851.1. XM_011250549.2.
XP_011248854.1. XM_011250552.2.
XP_011248855.1. XM_011250553.2.
XP_011248856.1. XM_011250554.2.
UniGeneiMm.97338.

3D structure databases

ProteinModelPortaliQ8VCK6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000052600.

Chemistry databases

BindingDBiQ8VCK6.
ChEMBLiCHEMBL3309047.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ8VCK6.
PhosphoSitePlusiQ8VCK6.

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.
OrthoDBiEOG091G0EX2.
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

BgeeiENSMUSG00000051314.
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...

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: November 2, 2016
This is version 109 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.