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Protein

Free fatty acid receptor 2

Gene

FFAR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processImmunity, Inflammatory response
LigandLipid-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000126262.4
HGNCiHGNC:4501 FFAR2
MIMi603823 gene
neXtProtiNX_O15552

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi167N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO15552
PeptideAtlasiO15552
PRIDEiO15552
ProteomicsDBi48754

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 Expressed in 95 organ(s), highest expression level in blood
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, 84 interactors
STRINGi9606.ENSP00000246549

Chemistry databases

BindingDBiO15552

Structurei

3D structure databases

ProteinModelPortaliO15552
SMRiO15552
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
GeneTreeiENSGT00920000148955
HOGENOMiHOG000026778
HOVERGENiHBG051811
InParanoidiO15552
KOiK04328
OMAiFVWIMLT
OrthoDBiEOG091G0EX2
PhylomeDBiO15552
TreeFamiTF350010

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR013312 GPR40-rel_orph
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01904 GPR40FAMILY
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 dbSNP:rs409093Ensembl.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

Similar proteinsi

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
SMRiO15552
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109125, 2 interactors
IntActiO15552, 84 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
ProteomicsDBi48754

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
EuPathDBiHostDB:ENSG00000126262.4
GeneCardsiFFAR2
H-InvDBiHIX0027605
HGNCiHGNC:4501 FFAR2
HPAiHPA023985
MIMi603823 gene
neXtProtiNX_O15552
OpenTargetsiENSG00000126262
PharmGKBiPA28890
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IITC Eukaryota
ENOG4111Q82 LUCA
GeneTreeiENSGT00920000148955
HOGENOMiHOG000026778
HOVERGENiHBG051811
InParanoidiO15552
KOiK04328
OMAiFVWIMLT
OrthoDBiEOG091G0EX2
PhylomeDBiO15552
TreeFamiTF350010

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii2867
PROiPR:O15552
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126262 Expressed in 95 organ(s), highest expression level in blood
CleanExiHS_FFAR2
ExpressionAtlasiO15552 baseline and differential
GenevisibleiO15552 HS

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR013312 GPR40-rel_orph
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01904 GPR40FAMILY
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFFAR2_HUMAN
AccessioniPrimary (citable) accession number: O15552
Secondary accession number(s): B0M0J9
, Q4VAZ3, Q4VAZ5, Q4VBL5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 143 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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Main funding by: National Institutes of Health

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