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UniProtKB - O14843 (FFAR3_HUMAN)

Protein

Free fatty acid receptor 3

Gene

FFAR3

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. 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 (PubMed:12711604). 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. 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. 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. Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably propionate, butyrate and pentanoate while acetate is a poor activator (PubMed:12496283, PubMed:12711604).4 Publications

GO - Molecular functioni

  • G protein-coupled receptor activity Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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:000001557

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000185897.6
HGNCiHGNC:4499 FFAR3
MIMi603821 gene
neXtProtiNX_O14843

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 – 19ExtracellularSequence analysisAdd BLAST19
Transmembranei20 – 40Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini41 – 47Cytoplasmic7
Transmembranei48 – 68Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini69 – 88ExtracellularSequence analysisAdd BLAST20
Transmembranei89 – 111Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini112 – 132CytoplasmicSequence analysisAdd BLAST21
Transmembranei133 – 153Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini154 – 178ExtracellularSequence analysisAdd BLAST25
Transmembranei179 – 199Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini200 – 222CytoplasmicSequence analysisAdd BLAST23
Transmembranei223 – 243Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini244 – 258ExtracellularSequence analysisAdd BLAST15
Transmembranei259 – 279Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini280 – 346CytoplasmicSequence analysisAdd BLAST67

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi146H → A: Partial loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi158D → N: Gain of SCFA-independent constitutive G protein-coupled receptor activity. 1 Publication1
Mutagenesisi185R → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi245H → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1
Mutagenesisi258R → A: Loss of SCFA-induced G protein-coupled receptor activity. 1 Publication1

Organism-specific databases

DisGeNETi2865
OpenTargetsiENSG00000185897
PharmGKBiPA28888

Chemistry databases

ChEMBLiCHEMBL5201
GuidetoPHARMACOLOGYi227

Polymorphism and mutation databases

BioMutaiFFAR3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000695691 – 346Free fatty acid receptor 3Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi88 ↔ 169PROSITE-ProRule annotation
Glycosylationi166N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO14843
PeptideAtlasiO14843
PRIDEiO14843
ProteomicsDBi48274

Expressioni

Tissue specificityi

Highest level in adipose tissue, and lower expression across all tissues tested. Expressed in sympathetic ganglia.2 Publications

Gene expression databases

BgeeiENSG00000185897 Expressed in 59 organ(s), highest expression level in blood
CleanExiHS_FFAR3
ExpressionAtlasiO14843 baseline and differential
GenevisibleiO14843 HS

Organism-specific databases

HPAiHPA044681

Interactioni

Protein-protein interaction databases

IntActiO14843, 13 interactors
STRINGi9606.ENSP00000328230

Chemistry databases

BindingDBiO14843

Structurei

3D structure databases

ProteinModelPortaliO14843
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
InParanoidiO14843
KOiK04326
OMAiAYPLWYK
OrthoDBiEOG091G0EX2
PhylomeDBiO14843
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.

O14843-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDTGPDQSYF SGNHWFVFSV YLLTFLVGLP LNLLALVVFV GKLQRRPVAV 
        60         70         80         90        100
DVLLLNLTAS DLLLLLFLPF RMVEAANGMH WPLPFILCPL SGFIFFTTIY 
       110        120        130        140        150
LTALFLAAVS IERFLSVAHP LWYKTRPRLG QAGLVSVACW LLASAHCSVV 
       160        170        180        190        200
YVIEFSGDIS HSQGTNGTCY LEFRKDQLAI LLPVRLEMAV VLFVVPLIIT 
       210        220        230        240        250
SYCYSRLVWI LGRGGSHRRQ RRVAGLLAAT LLNFLVCFGP YNVSHVVGYI 
       260        270        280        290        300
CGESPAWRIY VTLLSTLNSC VDPFVYYFSS SGFQADFHEL LRRLCGLWGQ 
       310        320        330        340 
WQQESSMELK EQKGGEEQRA DRPAERKTSE HSQGCGTGGQ VACAES
Length:346
Mass (Da):38,649
Last modified:January 1, 1998 - v1
Checksum:iB3B19D62D11B6BA1
GO

Polymorphismi

The 6 amino acid differences at positions 44, 45, 174, 227, 256 and 346 between GPR42 and FFAR3, are polymorphic in the human population. The frequency of the probable inactive allele of FFAR3, with a Trp at position 174 was estimated to 1%.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06285444Q → R1 PublicationCorresponds to variant dbSNP:rs382771Ensembl.1
Natural variantiVAR_06285545R → C1 PublicationCorresponds to variant dbSNP:rs1359000742Ensembl.1
Natural variantiVAR_062856174R → W Abolishes activation by propionate. 2 PublicationsCorresponds to variant dbSNP:rs1415955990Ensembl.1
Natural variantiVAR_062857227L → V1 PublicationCorresponds to variant dbSNP:rs1395869674Ensembl.1
Natural variantiVAR_062858256A → V1 PublicationCorresponds to variant dbSNP:rs1170582382Ensembl.1
Natural variantiVAR_062962346S → N1 PublicationCorresponds to variant dbSNP:rs201080710Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024688 Genomic DNA Translation: AAB86711.1
U62631 Genomic DNA No translation available.
BC035657 mRNA Translation: AAH35657.1
BC113695 mRNA Translation: AAI13696.1
BC148269 mRNA Translation: AAI48270.1
CCDSiCCDS12459.1
PIRiJC5715
RefSeqiNP_005295.1, NM_005304.4
UniGeneiHs.248055

Genome annotation databases

EnsembliENST00000327809; ENSP00000328230; ENSG00000185897
ENST00000594310; ENSP00000469522; ENSG00000185897
GeneIDi2865
KEGGihsa:2865
UCSCiuc002nzd.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024688 Genomic DNA Translation: AAB86711.1
U62631 Genomic DNA No translation available.
BC035657 mRNA Translation: AAH35657.1
BC113695 mRNA Translation: AAI13696.1
BC148269 mRNA Translation: AAI48270.1
CCDSiCCDS12459.1
PIRiJC5715
RefSeqiNP_005295.1, NM_005304.4
UniGeneiHs.248055

3D structure databases

ProteinModelPortaliO14843
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO14843, 13 interactors
STRINGi9606.ENSP00000328230

Chemistry databases

BindingDBiO14843
ChEMBLiCHEMBL5201
GuidetoPHARMACOLOGYi227
SwissLipidsiSLP:000001557

Protein family/group databases

GPCRDBiSearch...

Polymorphism and mutation databases

BioMutaiFFAR3

Proteomic databases

PaxDbiO14843
PeptideAtlasiO14843
PRIDEiO14843
ProteomicsDBi48274

Protocols and materials databases

DNASUi2865
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327809; ENSP00000328230; ENSG00000185897
ENST00000594310; ENSP00000469522; ENSG00000185897
GeneIDi2865
KEGGihsa:2865
UCSCiuc002nzd.4 human

Organism-specific databases

CTDi2865
DisGeNETi2865
EuPathDBiHostDB:ENSG00000185897.6
GeneCardsiFFAR3
HGNCiHGNC:4499 FFAR3
HPAiHPA044681
MIMi603821 gene
neXtProtiNX_O14843
OpenTargetsiENSG00000185897
PharmGKBiPA28888
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IITC Eukaryota
ENOG4111Q82 LUCA
GeneTreeiENSGT00920000148955
HOGENOMiHOG000026778
HOVERGENiHBG051811
InParanoidiO14843
KOiK04326
OMAiAYPLWYK
OrthoDBiEOG091G0EX2
PhylomeDBiO14843
TreeFamiTF350010

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiFree_fatty_acid_receptor_3
GenomeRNAii2865
PROiPR:O14843
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185897 Expressed in 59 organ(s), highest expression level in blood
CleanExiHS_FFAR3
ExpressionAtlasiO14843 baseline and differential
GenevisibleiO14843 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 nameiFFAR3_HUMAN
AccessioniPrimary (citable) accession number: O14843
Secondary accession number(s): B2RWM8, Q14CM7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 144 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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