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Protein

Free fatty acid receptor 1

Gene

FFAR1

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

Activity 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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
LigandLipid-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000126266.3
HGNCiHGNC:4498 FFAR1
MIMi603820 gene
neXtProtiNX_O14842

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 – 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

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...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO14842
PRIDEiO14842
ProteomicsDBi48273
TopDownProteomicsiO14842

PTM databases

iPTMnetiO14842
PhosphoSitePlusiO14842

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000126266 Expressed in 44 organ(s), highest expression level in right ovary
CleanExiHS_FFAR1
GenevisibleiO14842 HS

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9606.ENSP00000246553

Chemistry databases

BindingDBiO14842

Structurei

Secondary structure

1300
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00920000148955
HOGENOMiHOG000236290
HOVERGENiHBG080696
InParanoidiO14842
KOiK04325
OMAiRRPRYSW
OrthoDBiEOG091G0HSS
PhylomeDBiO14842
TreeFamiTF350010

Family and domain databases

CDDicd15169 7tmA_FFAR1, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR013312 GPR40-rel_orph
IPR013313 GPR40_recept_FA
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01905 FATTYACIDR
PR00237 GPCRRHODOPSN
PR01904 GPR40FAMILY
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 → H1 PublicationCorresponds to variant dbSNP:rs2301151Ensembl.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

Similar proteinsi

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[»]
5TZRX-ray2.20A1-211[»]
A214-300[»]
5TZYX-ray3.22A1-211[»]
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
ProteomicsDBi48273
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
EuPathDBiHostDB:ENSG00000126266.3
GeneCardsiFFAR1
HGNCiHGNC:4498 FFAR1
MIMi603820 gene
neXtProtiNX_O14842
OpenTargetsiENSG00000126266
PharmGKBiPA28887
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IV8D Eukaryota
ENOG4111572 LUCA
GeneTreeiENSGT00920000148955
HOGENOMiHOG000236290
HOVERGENiHBG080696
InParanoidiO14842
KOiK04325
OMAiRRPRYSW
OrthoDBiEOG091G0HSS
PhylomeDBiO14842
TreeFamiTF350010

Enzyme and pathway databases

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
PROiPR:O14842
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126266 Expressed in 44 organ(s), highest expression level in right ovary
CleanExiHS_FFAR1
GenevisibleiO14842 HS

Family and domain databases

CDDicd15169 7tmA_FFAR1, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR013312 GPR40-rel_orph
IPR013313 GPR40_recept_FA
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01905 FATTYACIDR
PR00237 GPCRRHODOPSN
PR01904 GPR40FAMILY
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFFAR1_HUMAN
AccessioniPrimary (citable) accession number: O14842
Secondary accession number(s): Q0VAS2, Q4VBL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 145 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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