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Protein

Free fatty acid receptor 3

Gene

Ffar3

Organism
Rattus norvegicus (Rat)
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 (PubMed:24305827). Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate. 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 (PubMed:24412651). May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion. 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. 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. Finally, may also play a role in glucose homeostasis. 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.3 Publications

GO - Molecular functioni

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

GO - Biological processi

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-RNO-416476. G alpha (q) signalling events.
R-RNO-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:Gpr41
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1311035. 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40R → Q: No effect on activation by propionate. 1 Publication1
Mutagenesisi41R → C: No effect on activation by propionate. 1 Publication1
Mutagenesisi170R → W: Loss of activation by propionate. 1 Publication1
Mutagenesisi223L → V: Constitutively active. 1 Publication1
Mutagenesisi252T → V: Reduced activation by propionate. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004303121 – 319Free fatty acid receptor 3Add BLAST319

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi84 ↔ 165PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiB2GV46.

Expressioni

Tissue specificityi

Expressed in the sympathetic nervous system.1 Publication

Gene expression databases

BgeeiENSRNOG00000037467.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000053557.

Structurei

3D structure databases

ProteinModelPortaliB2GV46.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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.
InParanoidiB2GV46.
KOiK04326.
OMAiNSCVDPL.
OrthoDBiEOG091G0EX2.
PhylomeDBiB2GV46.
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.

B2GV46-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTSFFPGNH WLFFSVDLLV FLVGLPLNVM ALVVFVNKLR RRPVAVDLLL
60 70 80 90 100
LNLTISDLLL LLFLPFRIVE AACGMKWILP FIFCPLSGFL FFTTIYLTSL
110 120 130 140 150
FLMTVSIERF LSVAYPLWYK TRPRLAQAGL VSGICWFLAS AHCSVIYVTE
160 170 180 190 200
YWGNATYSQG TNGTCYLEFR EDQLAILLPV RLEMAVVLFM VPLCITSYCY
210 220 230 240 250
SRLVWILSQG ASRRRRKRVM GLLVATLLIF FVCFGPYNMS HVVGYVRGES
260 270 280 290 300
PTWRSYVLLL STLNSCIDPL VFYFSSSKFQ ADFHQLLSRL IRACVPWTQE
310
VSLELKVKNG EEPSKECPS
Length:319
Mass (Da):36,483
Last modified:June 10, 2008 - v1
Checksum:i076C42FB2383161A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06004309 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM07705.1.
BC166522 mRNA. Translation: AAI66522.1.
RefSeqiNP_001102382.1. NM_001108912.1.
UniGeneiRn.122324.

Genome annotation databases

EnsembliENSRNOT00000056714; ENSRNOP00000053557; ENSRNOG00000037467.
GeneIDi365228.
KEGGirno:365228.
UCSCiRGD:1311035. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06004309 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM07705.1.
BC166522 mRNA. Translation: AAI66522.1.
RefSeqiNP_001102382.1. NM_001108912.1.
UniGeneiRn.122324.

3D structure databases

ProteinModelPortaliB2GV46.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000053557.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiB2GV46.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000056714; ENSRNOP00000053557; ENSRNOG00000037467.
GeneIDi365228.
KEGGirno:365228.
UCSCiRGD:1311035. rat.

Organism-specific databases

CTDi2865.
RGDi1311035. Ffar3.

Phylogenomic databases

eggNOGiENOG410IITC. Eukaryota.
ENOG4111Q82. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000026778.
HOVERGENiHBG051811.
InParanoidiB2GV46.
KOiK04326.
OMAiNSCVDPL.
OrthoDBiEOG091G0EX2.
PhylomeDBiB2GV46.
TreeFamiTF350010.

Enzyme and pathway databases

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

Miscellaneous databases

PROiB2GV46.

Gene expression databases

BgeeiENSRNOG00000037467.

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_RAT
AccessioniPrimary (citable) accession number: B2GV46
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 2014
Last sequence update: June 10, 2008
Last modified: September 7, 2016
This is version 62 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. 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.