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Protein

Free fatty acid receptor 4

Gene

Ffar4

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

Functioni

Receptor for medium and long-chain free fatty acids (FFAs). Signals via a G(q)/G(11)-coupled pathway. Acts as a receptor for omega-3 fatty acids and mediates robust anti-inflammatory effects, particularly in macrophages and fat cells. The anti-inflammatory effects involve inhibition of TAK1 through a beta-arrestin 2 (ARRB2)/TAB1-dependent effect, but independent of the G(q)/G(11)-coupled pathway. Mediates potent insulin sensitizing and antidiabetic effects by repressing macrophage-induced tissue inflammation. Mediates the taste of fatty acids. Mediates FFA-induced inhibition of apoptosis in enteroendocrine cells. May play a role in the regulation of adipocyte development and differentiation.5 Publications

GO - Molecular functioni

  • fatty acid binding Source: UniProtKB
  • G-protein coupled receptor activity Source: MGI
  • taste receptor activity Source: UniProtKB

GO - Biological processi

  • fat cell differentiation Source: CACAO
  • G-protein coupled receptor signaling pathway Source: MGI
  • hormone secretion Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cytokine secretion Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of glucose transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-MMU-444209. Free fatty acid receptors.

Chemistry databases

SwissLipidsiSLP:000001560.

Names & Taxonomyi

Protein namesi
Recommended name:
Free fatty acid receptor 4
Alternative name(s):
G-protein coupled receptor 120
G-protein coupled receptor GT01
Omega-3 fatty acid receptor 1
Gene namesi
Name:Ffar4
Synonyms:Gpr120, O3far1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2147577. Ffar4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 45ExtracellularSequence analysisAdd BLAST45
Transmembranei46 – 66Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini67 – 77CytoplasmicSequence analysisAdd BLAST11
Transmembranei78 – 98Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini99 – 103ExtracellularSequence analysis5
Transmembranei104 – 124Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini125 – 156CytoplasmicSequence analysisAdd BLAST32
Transmembranei157 – 177Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini178 – 204ExtracellularSequence analysisAdd BLAST27
Transmembranei205 – 225Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini226 – 268CytoplasmicSequence analysisAdd BLAST43
Transmembranei269 – 289Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini290 – 295ExtracellularSequence analysis6
Transmembranei296 – 316Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini317 – 361CytoplasmicSequence analysisAdd BLAST45

GO - Cellular componenti

  • endocytic vesicle Source: MGI
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Deficient mice show glucose intolerance, hyperinsulinemia and display insulin resistance and a reduced preference for fatty acids. When fed a high-fat diet, they develop obesity and have fatty liver with decreased adipocyte differentiation and lipogenesis, and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signaling and enhanced inflammation in adipose tissue.3 Publications

Chemistry databases

ChEMBLiCHEMBL2052036.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000696111 – 361Free fatty acid receptor 4Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi21N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Phosphorylated. FFA stimulation facilitates phosphorylation (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ7TMA4.
PRIDEiQ7TMA4.

PTM databases

iPTMnetiQ7TMA4.
PhosphoSitePlusiQ7TMA4.

Expressioni

Tissue specificityi

Expressed in the taste buds of the circumvallate and fungiform papillae, mainly in type II cells (at protein level). Abundant expression in the intestinal tract. Highly expressed in adipose tissue, including subcutaneous, perineral, mesentric and epididymal adipose tissue. Expressed in proinflammatory CD11c+ macrophages, mature adipocytes, RAW 264.7 cells and enteroendocrine L cells. Expressed in the epithelium of circumvallate papillae containing taste buds but not in the nonsensory lingual epithelium. High expression detected also in pituitary gland, lung and spleen. Negligible expression in muscle, liver, brain, heart, kidney and stomach.5 Publications

Developmental stagei

Expression detected in differentiated mature adipocytes, with levels increasing during late stage adipocyte differentiation. Not detected in preadipocytes.1 Publication

Inductioni

By high-fat diet in adipose tissue macrophages and in hepatic Kupffer cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000054200.
CleanExiMM_GPR120.
ExpressionAtlasiQ7TMA4. baseline and differential.
GenevisibleiQ7TMA4. MM.

Interactioni

Subunit structurei

Interacts with ARRB2 following docosahexaenoic acid (DHA) stimulation.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Arrb2Q91YI44EBI-2912413,EBI-994161

Protein-protein interaction databases

IntActiQ7TMA4. 1 interactor.
STRINGi10090.ENSMUSP00000063660.

Chemistry databases

BindingDBiQ7TMA4.

Structurei

3D structure databases

ProteinModelPortaliQ7TMA4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi67 – 71Poly-Arg5

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00390000009371.
HOVERGENiHBG051775.
InParanoidiQ7TMA4.
KOiK08425.
OMAiYSKILQI.
OrthoDBiEOG091G0CDY.
PhylomeDBiQ7TMA4.
TreeFamiTF336844.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q7TMA4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPECAQTTG PGPSHTLDQV NRTHFPFFSD VKGDHRLVLS VVETTVLGLI
60 70 80 90 100
FVVSLLGNVC ALVLVARRRR RGATASLVLN LFCADLLFTS AIPLVLVVRW
110 120 130 140 150
TEAWLLGPVV CHLLFYVMTM SGSVTILTLA AVSLERMVCI VRLRRGLSGP
160 170 180 190 200
GRRTQAALLA FIWGYSALAA LPLCILFRVV PQRLPGGDQE IPICTLDWPN
210 220 230 240 250
RIGEISWDVF FVTLNFLVPG LVIVISYSKI LQITKASRKR LTLSLAYSES
260 270 280 290 300
HQIRVSQQDY RLFRTLFLLM VSFFIMWSPI IITILLILIQ NFRQDLVIWP
310 320 330 340 350
SLFFWVVAFT FANSALNPIL YNMSLFRNEW RKIFCCFFFP EKGAIFTDTS
360
VRRNDLSVIS S
Length:361
Mass (Da):40,813
Last modified:October 1, 2003 - v1
Checksum:iD3A3F0BEB55F7B7B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB115769 mRNA. Translation: BAD83369.1.
AY288424 mRNA. Translation: AAP72133.1.
BC053698 mRNA. Translation: AAH53698.1.
CCDSiCCDS29783.1.
RefSeqiNP_861413.1. NM_181748.2.
UniGeneiMm.35288.

Genome annotation databases

EnsembliENSMUST00000067098; ENSMUSP00000063660; ENSMUSG00000054200.
GeneIDi107221.
KEGGimmu:107221.
UCSCiuc008hjc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB115769 mRNA. Translation: BAD83369.1.
AY288424 mRNA. Translation: AAP72133.1.
BC053698 mRNA. Translation: AAH53698.1.
CCDSiCCDS29783.1.
RefSeqiNP_861413.1. NM_181748.2.
UniGeneiMm.35288.

3D structure databases

ProteinModelPortaliQ7TMA4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ7TMA4. 1 interactor.
STRINGi10090.ENSMUSP00000063660.

Chemistry databases

BindingDBiQ7TMA4.
ChEMBLiCHEMBL2052036.
SwissLipidsiSLP:000001560.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ7TMA4.
PhosphoSitePlusiQ7TMA4.

Proteomic databases

PaxDbiQ7TMA4.
PRIDEiQ7TMA4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067098; ENSMUSP00000063660; ENSMUSG00000054200.
GeneIDi107221.
KEGGimmu:107221.
UCSCiuc008hjc.1. mouse.

Organism-specific databases

CTDi338557.
MGIiMGI:2147577. Ffar4.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00390000009371.
HOVERGENiHBG051775.
InParanoidiQ7TMA4.
KOiK08425.
OMAiYSKILQI.
OrthoDBiEOG091G0CDY.
PhylomeDBiQ7TMA4.
TreeFamiTF336844.

Enzyme and pathway databases

ReactomeiR-MMU-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-MMU-444209. Free fatty acid receptors.

Miscellaneous databases

PROiQ7TMA4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054200.
CleanExiMM_GPR120.
ExpressionAtlasiQ7TMA4. baseline and differential.
GenevisibleiQ7TMA4. MM.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFFAR4_MOUSE
AccessioniPrimary (citable) accession number: Q7TMA4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: October 1, 2003
Last modified: November 2, 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.