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Protein

Free fatty acid receptor 3

Gene

Ffar3

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. 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. Activated by SCFAs and by beta-hydroxybutyrate, a ketone body produced by the liver upon starvation, it inhibits N-type calcium channels and modulates the activity of sympathetic neurons through a signaling cascade involving the beta and gamma subunits of its coupled G protein, phospholipase C and MAP kinases. Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate (PubMed:21518883, PubMed:22673524). Upon activation by SCFAs accumulating in the intestine, it may also signal to the brain via neural circuits which in turn would regulate intestinal gluconeogenesis. May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion (PubMed:23401498). May also regulate secretion of the PYY peptide by enteroendocrine cells and control gut motility, intestinal transit rate, and the harvesting of energy from SCFAs produced by gut microbiota (PubMed:18931303). May also indirectly regulate the production of LEP/Leptin, a hormone acting on the CNS to inhibit food intake, in response to the presence of short-chain fatty acids in the intestine (PubMed:14722361, PubMed:20399779). Finally, may also play a role in glucose homeostasis (PubMed:22190648, PubMed:24748202). Besides its role in energy homeostasis, may play a role in intestinal immunity. May mediate the activation of the inflammatory and immune response by SCFAs in the gut, regulating the rapid production of chemokines and cytokines by intestinal epithelial cells (PubMed:23665276). Exhibits an SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).10 Publications

GO - Molecular functioni

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

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
  • cellular response to fatty acid Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • inflammatory response Source: UniProtKB-KW
  • mucosal immune response Source: UniProtKB
  • negative regulation of blood pressure Source: UniProtKB
  • positive regulation of action potential Source: MGI
  • 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 glucose import in response to insulin stimulus Source: UniProtKB
  • regulation of heart rate by chemical signal Source: MGI
  • regulation of hormone biosynthetic process Source: UniProtKB
  • regulation of norepinephrine secretion 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 3
Alternative name(s):
G-protein coupled receptor 41
Gene namesi
Name:Ffar3
Synonyms:Gm478, Gpr41
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2685324. Ffar3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 15ExtracellularSequence analysisAdd BLAST15
Transmembranei16 – 36Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini37 – 43CytoplasmicSequence analysis7
Transmembranei44 – 64Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini65 – 98ExtracellularSequence analysisAdd BLAST34
Transmembranei99 – 119Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini120 – 127CytoplasmicSequence analysis8
Transmembranei128 – 148Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini149 – 183ExtracellularSequence analysisAdd BLAST35
Transmembranei184 – 206Helical; Name=5Sequence analysisAdd BLAST23
Topological domaini207 – 218CytoplasmicSequence analysisAdd BLAST12
Transmembranei219 – 239Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini240 – 254ExtracellularSequence analysisAdd BLAST15
Transmembranei255 – 275Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini276 – 319CytoplasmicSequence analysisAdd BLAST44

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Knockout mice display a retarded growth of sympathetic innervation and the superior cervical ganglion is significantly smaller. A heart rate decrease is also observed together with altered secretion of cardiac noradrenaline that might be due to reduced sympathetic nerve activity. Contrary to wild-type mice, oxygen consumption is not modified by feeding or starvation (PubMed:21518883). They also display impaired SCFA-triggered glucagon-like peptide 1/GLP-1 secretion and impaired glucose tolerance (PubMed:22190648). Finally, knockout mice display altered protective intestinal inflammatory and immune responses. Otherwise, they display normal growth and no major morphological abnormalities. Body weight, heart weight to body weight ratio, and metabolic parameters are comparable. However, there might be a gender bias, the effect on energy expenditure and body fat content being male specific (PubMed:23110765).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi154N → D: Loss of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3309101.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002277831 – 319Free fatty acid receptor 3Add BLAST319

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi84 ↔ 165PROSITE-ProRule annotation
Glycosylationi154N-linked (GlcNAc...)Sequence analysis1
Glycosylationi162N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ3UFD7.
PRIDEiQ3UFD7.

Expressioni

Tissue specificityi

Expressed in white adipose tissue and skeletal muscle (at protein level). Abundantly expressed in sympathetic ganglia such as the superior cervical ganglion. Also expressed by intestinal endocrine cells.5 Publications

Developmental stagei

Expressed in sympathetic ganglia and trunks at E13.5, E15.5 and P1. Up-regulated during myocyte and adipocyte differentiation (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000019429.
CleanExiMM_FFAR3.
ExpressionAtlasiQ3UFD7. baseline and differential.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092163.

Chemistry databases

BindingDBiQ3UFD7.

Structurei

3D structure databases

ProteinModelPortaliQ3UFD7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi213 – 218Poly-Arg6

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.
InParanoidiQ3UFD7.
KOiK04326.
OMAiNSCVDPL.
OrthoDBiEOG091G0EX2.
PhylomeDBiQ3UFD7.
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.

Q3UFD7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTSFFLGNY WLFFSVYLLV FLVGLPLNVM ALVVFVGKLR RRPVAVDLLL
60 70 80 90 100
LNLTISDLLL LLFLPFRMVE AACGMRWLLP FIFCPLSGFL FFTTIYLTSL
110 120 130 140 150
FLTAVSIERF LSVAYPLWYK TRPRLAQAGL VSVVCWFLAS AHCSVVYITE
160 170 180 190 200
YWGNATYSQG TNGTCYLEFR EDQLAILLPV RLEMAVVLFM VPLCITSYCY
210 220 230 240 250
SRLVWILSRG ASRRRRKRIM GLLAATLLIF FVCFGPYNMS HVVGYVSRES
260 270 280 290 300
PSWRSYVLLL STLNSCIDPL VFYFSSSKFQ ADFHQLLGRL LRTCVPWTQQ
310
VSLELKVKNG EEPSKECPS
Length:319
Mass (Da):36,501
Last modified:October 11, 2005 - v1
Checksum:iB049EC4A8BFEDCC4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK148616 mRNA. Translation: BAE28624.1.
CCDSiCCDS21112.1.
RefSeqiNP_001028488.1. NM_001033316.2.
UniGeneiMm.291167.

Genome annotation databases

EnsembliENSMUST00000094583; ENSMUSP00000092163; ENSMUSG00000019429.
ENSMUST00000185748; ENSMUSP00000140252; ENSMUSG00000019429.
GeneIDi233080.
KEGGimmu:233080.
UCSCiuc009ggp.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK148616 mRNA. Translation: BAE28624.1.
CCDSiCCDS21112.1.
RefSeqiNP_001028488.1. NM_001033316.2.
UniGeneiMm.291167.

3D structure databases

ProteinModelPortaliQ3UFD7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092163.

Chemistry databases

BindingDBiQ3UFD7.
ChEMBLiCHEMBL3309101.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiQ3UFD7.
PRIDEiQ3UFD7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000094583; ENSMUSP00000092163; ENSMUSG00000019429.
ENSMUST00000185748; ENSMUSP00000140252; ENSMUSG00000019429.
GeneIDi233080.
KEGGimmu:233080.
UCSCiuc009ggp.1. mouse.

Organism-specific databases

CTDi2865.
MGIiMGI:2685324. Ffar3.

Phylogenomic databases

eggNOGiENOG410IITC. Eukaryota.
ENOG4111Q82. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000026778.
HOVERGENiHBG051811.
InParanoidiQ3UFD7.
KOiK04326.
OMAiNSCVDPL.
OrthoDBiEOG091G0EX2.
PhylomeDBiQ3UFD7.
TreeFamiTF350010.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ3UFD7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019429.
CleanExiMM_FFAR3.
ExpressionAtlasiQ3UFD7. baseline and differential.

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 nameiFFAR3_MOUSE
AccessioniPrimary (citable) accession number: Q3UFD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 11, 2005
Last modified: November 2, 2016
This is version 84 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.