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Protein

Free fatty acid receptor 4

Gene

FFAR4

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

Functioni

Receptor for medium and long-chain free fatty acids (FFAs). Signals via a G(q)/G(11)-coupled pathway. Acts as a receptor for omega-3 fatty acids and mediates robust anti-inflammatory effects, particularly in macrophages and fat cells. The anti-inflammatory effects involve inhibition of TAK1 through a beta-arrestin 2 (ARRB2)/TAB1-dependent effect, but independent of the G(q)/G(11)-coupled pathway. Mediates potent insulin sensitizing and antidiabetic effects by repressing macrophage-induced tissue inflammation. May mediate the taste of fatty acids. Mediates FFA-induced inhibition of apoptosis in enteroendocrine cells. May play a role in the regulation of adipocyte development and differentiation.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiREACT_21268. Free fatty acid receptors.
REACT_24019. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Names & Taxonomyi

Protein namesi
Recommended name:
Free fatty acid receptor 4
Alternative name(s):
G-protein coupled receptor 120
G-protein coupled receptor 129
G-protein coupled receptor GT01
G-protein coupled receptor PGR4
Omega-3 fatty acid receptor 1
Gene namesi
Name:FFAR4
Synonyms:GPR120, GPR129, O3FAR1, PGR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:19061. FFAR4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4545ExtracellularSequence AnalysisAdd
BLAST
Transmembranei46 – 6621Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini67 – 7711CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei78 – 9821Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini99 – 11214ExtracellularSequence AnalysisAdd
BLAST
Transmembranei113 – 13321Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini134 – 15623CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei157 – 17721Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini178 – 20427ExtracellularSequence AnalysisAdd
BLAST
Transmembranei205 – 22521Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini226 – 28459CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei285 – 30521Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini306 – 3116ExtracellularSequence Analysis
Transmembranei312 – 33221Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini333 – 37745CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

MIMi607514. phenotype.
PharmGKBiPA134924595.

Polymorphism and mutation databases

BioMutaiFFAR4.
DMDMi82581671.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 377377Free fatty acid receptor 4PRO_0000069610Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi21 – 211N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Phosphorylated. FFA stimulation facilitates phosphorylation.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ5NUL3.
PRIDEiQ5NUL3.

PTM databases

PhosphoSiteiQ5NUL3.

Expressioni

Tissue specificityi

Abundant expression in the intestinal tract. Highly expressed in adipose tissue, small intestine and pancreas.2 Publications

Developmental stagei

Expression detected in differentiated adipocytes but not in preadipocytes.1 Publication

Gene expression databases

BgeeiQ5NUL3.
CleanExiHS_GPR120.
ExpressionAtlasiQ5NUL3. baseline and differential.
GenevisibleiQ5NUL3. HS.

Organism-specific databases

HPAiHPA042563.

Interactioni

Subunit structurei

Interacts with ARRB2 following docosahexaenoic acid (DHA) stimulation.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000360538.

Structurei

3D structure databases

ProteinModelPortaliQ5NUL3.
SMRiQ5NUL3. Positions 37-337.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi67 – 715Poly-Arg

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG241328.
GeneTreeiENSGT00390000009371.
HOVERGENiHBG051775.
InParanoidiQ5NUL3.
KOiK08425.
OMAiYSKILQI.
OrthoDBiEOG7PK900.
PhylomeDBiQ5NUL3.
TreeFamiTF336844.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5NUL3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI
60 70 80 90 100
FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFIS AIPLVLAVRW
110 120 130 140 150
TEAWLLGPVA CHLLFYVMTL SGSVTILTLA AVSLERMVCI VHLQRGVRGP
160 170 180 190 200
GRRARAVLLA LIWGYSAVAA LPLCVFFRVV PQRLPGADQE ISICTLIWPT
210 220 230 240 250
IPGEISWDVS FVTLNFLVPG LVIVISYSKI LQTSEHLLDA RAVVTHSEIT
260 270 280 290 300
KASRKRLTVS LAYSESHQIR VSQQDFRLFR TLFLLMVSFF IMWSPIIITI
310 320 330 340 350
LLILIQNFKQ DLVIWPSLFF WVVAFTFANS ALNPILYNMT LCRNEWKKIF
360 370
CCFWFPEKGA ILTDTSVKRN DLSIISG
Note: Specific to human.
Length:377
Mass (Da):42,241
Last modified:May 10, 2005 - v2
Checksum:i28BB8C3A939A7EFF
GO
Isoform 2 (identifier: Q5NUL3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     233-248: Missing.

Show »
Length:361
Mass (Da):40,494
Checksum:iE90BD5D64D9E6E78
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671Missing in AAP72126 (PubMed:14623098).Curated
Sequence conflicti274 – 2741Q → H in BAD83368 (PubMed:15619630).Curated
Sequence conflicti297 – 2971I → T in BAD83368 (PubMed:15619630).Curated

Polymorphismi

Genetic variations in FFAR4 define the body mass index quantitative trait locus 10 (BMIQ10) [MIMi:607514]. Variance in body mass index is a susceptibility factor for obesity.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti67 – 671R → C.2 Publications
Corresponds to variant rs61866610 [ dbSNP | Ensembl ].
VAR_067799
Natural varianti270 – 2701R → H Polymorphism associated with increased risk of obesity. 1 Publication
Corresponds to variant rs116454156 [ dbSNP | Ensembl ].
VAR_067800

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei233 – 24816Missing in isoform 2. 2 PublicationsVSP_013684Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY288417 mRNA. Translation: AAP72126.1.
AB115768 mRNA. Translation: BAD83368.1.
AL356214 Genomic DNA. Translation: CAH72326.1.
AL356214 Genomic DNA. Translation: CAH72327.1.
CH471066 Genomic DNA. Translation: EAW50069.1.
BC101175 mRNA. Translation: AAI01176.1.
AY255573 mRNA. Translation: AAO85085.1.
CCDSiCCDS31248.1. [Q5NUL3-1]
CCDS55720.1. [Q5NUL3-2]
RefSeqiNP_001182684.1. NM_001195755.1. [Q5NUL3-2]
NP_859529.2. NM_181745.3. [Q5NUL3-1]
UniGeneiHs.661022.

Genome annotation databases

EnsembliENST00000371481; ENSP00000360536; ENSG00000186188. [Q5NUL3-2]
ENST00000371483; ENSP00000360538; ENSG00000186188. [Q5NUL3-1]
GeneIDi338557.
KEGGihsa:338557.
UCSCiuc010qnt.2. human. [Q5NUL3-1]
uc010qnu.2. human. [Q5NUL3-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY288417 mRNA. Translation: AAP72126.1.
AB115768 mRNA. Translation: BAD83368.1.
AL356214 Genomic DNA. Translation: CAH72326.1.
AL356214 Genomic DNA. Translation: CAH72327.1.
CH471066 Genomic DNA. Translation: EAW50069.1.
BC101175 mRNA. Translation: AAI01176.1.
AY255573 mRNA. Translation: AAO85085.1.
CCDSiCCDS31248.1. [Q5NUL3-1]
CCDS55720.1. [Q5NUL3-2]
RefSeqiNP_001182684.1. NM_001195755.1. [Q5NUL3-2]
NP_859529.2. NM_181745.3. [Q5NUL3-1]
UniGeneiHs.661022.

3D structure databases

ProteinModelPortaliQ5NUL3.
SMRiQ5NUL3. Positions 37-337.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000360538.

Chemistry

BindingDBiQ5NUL3.
ChEMBLiCHEMBL5339.
GuidetoPHARMACOLOGYi127.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ5NUL3.

Polymorphism and mutation databases

BioMutaiFFAR4.
DMDMi82581671.

Proteomic databases

PaxDbiQ5NUL3.
PRIDEiQ5NUL3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371481; ENSP00000360536; ENSG00000186188. [Q5NUL3-2]
ENST00000371483; ENSP00000360538; ENSG00000186188. [Q5NUL3-1]
GeneIDi338557.
KEGGihsa:338557.
UCSCiuc010qnt.2. human. [Q5NUL3-1]
uc010qnu.2. human. [Q5NUL3-2]

Organism-specific databases

CTDi338557.
GeneCardsiGC10P095329.
HGNCiHGNC:19061. FFAR4.
HPAiHPA042563.
MIMi607514. phenotype.
609044. gene.
neXtProtiNX_Q5NUL3.
PharmGKBiPA134924595.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG241328.
GeneTreeiENSGT00390000009371.
HOVERGENiHBG051775.
InParanoidiQ5NUL3.
KOiK08425.
OMAiYSKILQI.
OrthoDBiEOG7PK900.
PhylomeDBiQ5NUL3.
TreeFamiTF336844.

Enzyme and pathway databases

ReactomeiREACT_21268. Free fatty acid receptors.
REACT_24019. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Miscellaneous databases

GeneWikiiGPR120.
GenomeRNAii338557.
NextBioi97032.
PROiQ5NUL3.
SOURCEiSearch...

Gene expression databases

BgeeiQ5NUL3.
CleanExiHS_GPR120.
ExpressionAtlasiQ5NUL3. baseline and differential.
GenevisibleiQ5NUL3. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives."
    Fredriksson R., Hoeglund P.J., Gloriam D.E.I., Lagerstroem M.C., Schioeth H.B.
    FEBS Lett. 554:381-388(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120."
    Hirasawa A., Tsumaya K., Awaji T., Katsuma S., Adachi T., Yamada M., Sugimoto Y., Miyazaki S., Tsujimoto G.
    Nat. Med. 11:90-94(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, VARIANT CYS-67.
  3. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 49-312 (ISOFORM 2).
  7. Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  8. "Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor."
    Burns R.N., Moniri N.H.
    Biochem. Biophys. Res. Commun. 396:1030-1035(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  9. Cited for: INVOLVEMENT IN BMIQ10, VARIANTS CYS-67 AND HIS-270, ASSOCIATION OF VARIANT HIS-270 WITH RISK OF OBESITY.

Entry informationi

Entry nameiFFAR4_HUMAN
AccessioniPrimary (citable) accession number: Q5NUL3
Secondary accession number(s): Q495H1
, Q5VY25, Q5VY26, Q7Z605, Q86SM7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: June 24, 2015
This is version 100 of the entry and version 2 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

Miscellaneous

It has been shown that FFA alpha-linolenic acid stimulates secretion of glucagon-like peptide 1 (GLP-1) from the gastro-intestinal tract (PubMed:15619630). However, this ligand is an agonist of both FFAR4 and FFAR1 and the latter has been shown to mediate GLP-1 release too (PubMed:18519800). So the precise role of FFAR4 in mediating needs to be confirmed.1 Publication

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 10
    Human chromosome 10: 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

External Data

Dasty 3

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 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.