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Protein

Free fatty acid receptor 2

Gene

FFAR2

Organism
Homo sapiens (Human)
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:12496283, PubMed:12711604, 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. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. 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. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. 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 (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).7 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

BioCyciZFISH:ENSG00000126262-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-444209. Free fatty acid receptors.

Chemistry databases

SwissLipidsiSLP:000001558.

Names & Taxonomyi

Protein namesi
Recommended name:
Free fatty acid receptor 2
Alternative name(s):
G-protein coupled receptor 43
Gene namesi
Name:FFAR2
Synonyms:FFA2, GPCR43, GPR43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:4501. FFAR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12ExtracellularSequence analysisAdd BLAST12
Transmembranei13 – 33Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini34 – 41Cytoplasmic8
Transmembranei42 – 62Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini63 – 84ExtracellularSequence analysisAdd BLAST22
Transmembranei85 – 105Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini106 – 126CytoplasmicSequence analysisAdd BLAST21
Transmembranei127 – 147Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini148 – 173ExtracellularSequence analysisAdd BLAST26
Transmembranei174 – 194Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini195 – 219CytoplasmicSequence analysisAdd BLAST25
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

  • cell projection Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 2 Publications1
Mutagenesisi90Y → W: Complete loss of acetate-induced G protein-coupled receptor activity. 2 Publications1
Mutagenesisi106E → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi108Y → A: Complete loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi140H → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 2 Publications1
Mutagenesisi148Q → A: No effect on SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi148Q → E: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi159G → E: Partial loss of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication1
Mutagenesisi165Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi180R → A, K, L or S: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications1
Mutagenesisi238Y → A: Partial loss of propionate-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi239N → A: Complete loss of acetate-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi242H → A or F: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications1
Mutagenesisi255R → A: Complete loss of SCFA-induced G protein-coupled receptor activity. 3 Publications1

Organism-specific databases

DisGeNETi2867.
OpenTargetsiENSG00000126262.
PharmGKBiPA28890.

Chemistry databases

ChEMBLiCHEMBL5493.
GuidetoPHARMACOLOGYi226.

Polymorphism and mutation databases

BioMutaiFFAR2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000695711 – 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

PaxDbiO15552.
PeptideAtlasiO15552.
PRIDEiO15552.

PTM databases

iPTMnetiO15552.
PhosphoSitePlusiO15552.

Expressioni

Tissue specificityi

Expressed at relatively high levels in peripheral blood leukocytes and, to lesser extent, in spleen.2 Publications

Gene expression databases

BgeeiENSG00000126262.
CleanExiHS_FFAR2.
ExpressionAtlasiO15552. baseline and differential.
GenevisibleiO15552. HS.

Organism-specific databases

HPAiHPA023985.

Interactioni

Subunit structurei

Interacts with FCN1 (via Fibrinogen C-terminal domain).1 Publication

Protein-protein interaction databases

BioGridi109125. 2 interactors.
IntActiO15552. 3 interactors.
STRINGi9606.ENSP00000246549.

Chemistry databases

BindingDBiO15552.

Structurei

3D structure databases

ProteinModelPortaliO15552.
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.
InParanoidiO15552.
KOiK04328.
OMAiGHCTIVI.
OrthoDBiEOG091G0EX2.
PhylomeDBiO15552.
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.

O15552-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPDWKSSLI LMAYIIIFLT GLPANLLALR AFVGRIRQPQ PAPVHILLLS
60 70 80 90 100
LTLADLLLLL LLPFKIIEAA SNFRWYLPKV VCALTSFGFY SSIYCSTWLL
110 120 130 140 150
AGISIERYLG VAFPVQYKLS RRPLYGVIAA LVAWVMSFGH CTIVIIVQYL
160 170 180 190 200
NTTEQVRSGN EITCYENFTD NQLDVVLPVR LELCLVLFFI PMAVTIFCYW
210 220 230 240 250
RFVWIMLSQP LVGAQRRRRA VGLAVVTLLN FLVCFGPYNV SHLVGYHQRK
260 270 280 290 300
SPWWRSIAVV FSSLNASLDP LLFYFSSSVV RRAFGRGLQV LRNQGSSLLG
310 320 330
RRGKDTAEGT NEDRGVGQGE GMPSSDFTTE
Length:330
Mass (Da):37,144
Last modified:January 1, 1998 - v1
Checksum:iF4A8AC6AFBDF1E90
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti227T → M in AAH96201 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011861211L → H.Corresponds to variant rs409093dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024690 Genomic DNA. Translation: AAB86713.1.
AC002511 Genomic DNA. Translation: AAB67886.1.
EU432114 Genomic DNA. Translation: ABY87913.1.
BC095535 mRNA. Translation: AAH95535.1.
BC096198 mRNA. Translation: AAH96198.1.
BC096199 mRNA. Translation: AAH96199.1.
BC096200 mRNA. Translation: AAH96200.1.
BC096201 mRNA. Translation: AAH96201.1.
CCDSiCCDS12461.1.
PIRiJC5717.
RefSeqiNP_005297.1. NM_005306.2.
XP_016882198.1. XM_017026709.1.
XP_016882199.1. XM_017026710.1.
XP_016882200.1. XM_017026711.1.
UniGeneiHs.248056.

Genome annotation databases

EnsembliENST00000246549; ENSP00000246549; ENSG00000126262.
ENST00000599180; ENSP00000473159; ENSG00000126262.
GeneIDi2867.
KEGGihsa:2867.
UCSCiuc010eea.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024690 Genomic DNA. Translation: AAB86713.1.
AC002511 Genomic DNA. Translation: AAB67886.1.
EU432114 Genomic DNA. Translation: ABY87913.1.
BC095535 mRNA. Translation: AAH95535.1.
BC096198 mRNA. Translation: AAH96198.1.
BC096199 mRNA. Translation: AAH96199.1.
BC096200 mRNA. Translation: AAH96200.1.
BC096201 mRNA. Translation: AAH96201.1.
CCDSiCCDS12461.1.
PIRiJC5717.
RefSeqiNP_005297.1. NM_005306.2.
XP_016882198.1. XM_017026709.1.
XP_016882199.1. XM_017026710.1.
XP_016882200.1. XM_017026711.1.
UniGeneiHs.248056.

3D structure databases

ProteinModelPortaliO15552.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109125. 2 interactors.
IntActiO15552. 3 interactors.
STRINGi9606.ENSP00000246549.

Chemistry databases

BindingDBiO15552.
ChEMBLiCHEMBL5493.
GuidetoPHARMACOLOGYi226.
SwissLipidsiSLP:000001558.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO15552.
PhosphoSitePlusiO15552.

Polymorphism and mutation databases

BioMutaiFFAR2.

Proteomic databases

PaxDbiO15552.
PeptideAtlasiO15552.
PRIDEiO15552.

Protocols and materials databases

DNASUi2867.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246549; ENSP00000246549; ENSG00000126262.
ENST00000599180; ENSP00000473159; ENSG00000126262.
GeneIDi2867.
KEGGihsa:2867.
UCSCiuc010eea.4. human.

Organism-specific databases

CTDi2867.
DisGeNETi2867.
GeneCardsiFFAR2.
H-InvDBHIX0027605.
HGNCiHGNC:4501. FFAR2.
HPAiHPA023985.
MIMi603823. gene.
neXtProtiNX_O15552.
OpenTargetsiENSG00000126262.
PharmGKBiPA28890.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IITC. Eukaryota.
ENOG4111Q82. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000026778.
HOVERGENiHBG051811.
InParanoidiO15552.
KOiK04328.
OMAiGHCTIVI.
OrthoDBiEOG091G0EX2.
PhylomeDBiO15552.
TreeFamiTF350010.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000126262-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-444209. Free fatty acid receptors.

Miscellaneous databases

GenomeRNAii2867.
PROiO15552.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126262.
CleanExiHS_FFAR2.
ExpressionAtlasiO15552. baseline and differential.
GenevisibleiO15552. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O15552
Secondary accession number(s): B0M0J9
, Q4VAZ3, Q4VAZ5, Q4VBL5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.