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Protein

Free fatty acid receptor 1

Gene

FFAR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (By similarity). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway.By similarity3 Publications

Enzyme regulationi

The receptor is strongly activated by gamma-linolenic acid, while myristate gives a lower response. It is also activated by phytanic acid and pristanic acid (PubMed:21570468). Is also activated by synthetic agonists, such as TAK-875 (fasiglifam); this compound is a partial agonist and potentiates the activity of the endogenous ligand gamma-linolenic acid (PubMed:24130766).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei145Important for receptor activation1 Publication1
Sitei172Important for receptor activation1 Publication1
Binding sitei183Agonist1 Publication1
Binding sitei240Agonist1 Publication1
Binding sitei258Agonist1 Publication1

GO - Molecular functioni

  • bioactive lipid receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: ProtInc
  • guanyl-nucleotide exchange factor activity Source: Reactome
  • lipid binding Source: UniProtKB-KW

GO - Biological processi

  • glucose homeostasis Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • insulin secretion Source: Ensembl
  • positive regulation of calcium ion transport Source: UniProtKB
  • positive regulation of insulin secretion Source: Ensembl
  • response to fatty acid Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000126266-MONOMER.
ReactomeiR-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-HSA-400511. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
R-HSA-416476. G alpha (q) signalling events.
R-HSA-434316. Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion.
R-HSA-444209. Free fatty acid receptors.
SIGNORiO14842.

Chemistry databases

SwissLipidsiSLP:000001550.

Names & Taxonomyi

Protein namesi
Recommended name:
Free fatty acid receptor 1
Alternative name(s):
G-protein coupled receptor 40
Gene namesi
Name:FFAR1
Synonyms:GPR40
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:4498. FFAR1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8ExtracellularSequence analysis1 Publication8
Transmembranei9 – 31Helical; Name=1Sequence analysis1 PublicationAdd BLAST23
Topological domaini32 – 41CytoplasmicSequence analysis1 Publication10
Transmembranei42 – 64Helical; Name=2Sequence analysis1 PublicationAdd BLAST23
Topological domaini65 – 79ExtracellularSequence analysis1 PublicationAdd BLAST15
Transmembranei80 – 101Helical; Name=3Sequence analysis1 PublicationAdd BLAST22
Topological domaini102 – 121CytoplasmicSequence analysis1 PublicationAdd BLAST20
Transmembranei122 – 142Helical; Name=4Sequence analysis1 PublicationAdd BLAST21
Topological domaini143 – 178ExtracellularSequence analysis1 PublicationAdd BLAST36
Transmembranei179 – 200Helical; Name=5Sequence analysis1 PublicationAdd BLAST22
Topological domaini201 – 223CytoplasmicSequence analysis1 PublicationAdd BLAST23
Transmembranei224 – 248Helical; Name=6Sequence analysis1 PublicationAdd BLAST25
Topological domaini249 – 256ExtracellularSequence analysis1 Publication8
Transmembranei257 – 279Helical; Name=7Sequence analysis1 PublicationAdd BLAST23
Topological domaini280 – 300CytoplasmicSequence analysis1 PublicationAdd BLAST21

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12Y → A: Reduces cell surface expression and response to linolenic acid and synthetic agonists. 1 Publication1
Mutagenesisi91Y → A: Reduces response to linolenic acid. Reduces response to synthetic agonists. 2 Publications1
Mutagenesisi137H → A: Reduces response to linolenic acid. Reduces response to synthetic agonists. 2 Publications1
Mutagenesisi145E → A: Constitutive receptor signaling. 1 Publication1
Mutagenesisi172E → A: Constitutive receptor signaling. 1 Publication1
Mutagenesisi183R → A: Reduces response to linolenic acid. Strongly reduces response to synthetic agonists. 2 Publications1
Mutagenesisi240Y → A: Reduces response to linolenic acid. Reduces response to synthetic agonists. 2 Publications1
Mutagenesisi244N → A: Reduces response to linolenic acid. Reduces response to synthetic agonists. 2 Publications1
Mutagenesisi258R → A: Strongly reduces response to linolenic acid. Strongly reduces response to synthetic agonists. 2 Publications1
Mutagenesisi258R → K: Reduces response to linolenic acid. Strongly reduces response to synthetic agonists. 1 Publication1

Organism-specific databases

DisGeNETi2864.
OpenTargetsiENSG00000126266.
PharmGKBiPA28887.

Chemistry databases

ChEMBLiCHEMBL4422.
DrugBankiDB00159. Icosapent.
GuidetoPHARMACOLOGYi225.

Polymorphism and mutation databases

BioMutaiFFAR1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000695671 – 300Free fatty acid receptor 1Add BLAST300

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi79 ↔ 1701 Publication
Glycosylationi155N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO14842.
PRIDEiO14842.
TopDownProteomicsiO14842.

PTM databases

iPTMnetiO14842.
PhosphoSitePlusiO14842.

Expressioni

Tissue specificityi

Detected in brain and pancreas. Detected in pancreatic beta cells.2 Publications

Gene expression databases

BgeeiENSG00000126266.
CleanExiHS_FFAR1.
GenevisibleiO14842. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000246553.

Chemistry databases

BindingDBiO14842.

Structurei

Secondary structure

1300
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 36Combined sources32
Helixi40 – 67Combined sources28
Turni68 – 70Combined sources3
Helixi78 – 109Combined sources32
Helixi121 – 145Combined sources25
Beta strandi149 – 151Combined sources3
Beta strandi169 – 171Combined sources3
Helixi176 – 190Combined sources15
Helixi192 – 210Combined sources19
Helixi214 – 235Combined sources22
Helixi237 – 249Combined sources13
Helixi256 – 266Combined sources11
Helixi268 – 275Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PHUX-ray2.33A1-211[»]
A214-300[»]
ProteinModelPortaliO14842.
SMRiO14842.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni87 – 91Agonist binding1 Publication5

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IV8D. Eukaryota.
ENOG4111572. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000236290.
HOVERGENiHBG080696.
InParanoidiO14842.
KOiK04325.
OMAiLHLGCSD.
OrthoDBiEOG091G0HSS.
PhylomeDBiO14842.
TreeFamiTF350010.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
IPR013313. GPR40_recept_FA.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01905. FATTYACIDR.
PR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14842-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLPPQLSFG LYVAAFALGF PLNVLAIRGA TAHARLRLTP SLVYALNLGC
60 70 80 90 100
SDLLLTVSLP LKAVEALASG AWPLPASLCP VFAVAHFFPL YAGGGFLAAL
110 120 130 140 150
SAGRYLGAAF PLGYQAFRRP CYSWGVCAAI WALVLCHLGL VFGLEAPGGW
160 170 180 190 200
LDHSNTSLGI NTPVNGSPVC LEAWDPASAG PARFSLSLLL FFLPLAITAF
210 220 230 240 250
CYVGCLRALA RSGLTHRRKL RAAWVAGGAL LTLLLCVGPY NASNVASFLY
260 270 280 290 300
PNLGGSWRKL GLITGAWSVV LNPLVTGYLG RGPGLKTVCA ARTQGGKSQK
Length:300
Mass (Da):31,457
Last modified:January 1, 1998 - v1
Checksum:i77EF27DACD93E80B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24V → A in AAH95536 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020076211R → H.1 PublicationCorresponds to variant rs2301151dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024687 Genomic DNA. Translation: AAB86710.1.
BC095536 mRNA. Translation: AAH95536.1.
BC120944 mRNA. Translation: AAI20945.1.
CCDSiCCDS12458.1.
PIRiJC5714.
RefSeqiNP_005294.1. NM_005303.2.
UniGeneiHs.248127.

Genome annotation databases

EnsembliENST00000246553; ENSP00000246553; ENSG00000126266.
GeneIDi2864.
KEGGihsa:2864.
UCSCiuc002nzc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024687 Genomic DNA. Translation: AAB86710.1.
BC095536 mRNA. Translation: AAH95536.1.
BC120944 mRNA. Translation: AAI20945.1.
CCDSiCCDS12458.1.
PIRiJC5714.
RefSeqiNP_005294.1. NM_005303.2.
UniGeneiHs.248127.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PHUX-ray2.33A1-211[»]
A214-300[»]
ProteinModelPortaliO14842.
SMRiO14842.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000246553.

Chemistry databases

BindingDBiO14842.
ChEMBLiCHEMBL4422.
DrugBankiDB00159. Icosapent.
GuidetoPHARMACOLOGYi225.
SwissLipidsiSLP:000001550.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO14842.
PhosphoSitePlusiO14842.

Polymorphism and mutation databases

BioMutaiFFAR1.

Proteomic databases

PaxDbiO14842.
PRIDEiO14842.
TopDownProteomicsiO14842.

Protocols and materials databases

DNASUi2864.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246553; ENSP00000246553; ENSG00000126266.
GeneIDi2864.
KEGGihsa:2864.
UCSCiuc002nzc.3. human.

Organism-specific databases

CTDi2864.
DisGeNETi2864.
GeneCardsiFFAR1.
HGNCiHGNC:4498. FFAR1.
MIMi603820. gene.
neXtProtiNX_O14842.
OpenTargetsiENSG00000126266.
PharmGKBiPA28887.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IV8D. Eukaryota.
ENOG4111572. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000236290.
HOVERGENiHBG080696.
InParanoidiO14842.
KOiK04325.
OMAiLHLGCSD.
OrthoDBiEOG091G0HSS.
PhylomeDBiO14842.
TreeFamiTF350010.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000126266-MONOMER.
ReactomeiR-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-HSA-400511. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
R-HSA-416476. G alpha (q) signalling events.
R-HSA-434316. Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion.
R-HSA-444209. Free fatty acid receptors.
SIGNORiO14842.

Miscellaneous databases

GeneWikiiFree_fatty_acid_receptor_1.
GenomeRNAii2864.
PROiO14842.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126266.
CleanExiHS_FFAR1.
GenevisibleiO14842. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR013312. GPR40-rel_orph.
IPR013313. GPR40_recept_FA.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01905. FATTYACIDR.
PR00237. GPCRRHODOPSN.
PR01904. GPR40FAMILY.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFFAR1_HUMAN
AccessioniPrimary (citable) accession number: O14842
Secondary accession number(s): Q0VAS2, Q4VBL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 134 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.