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Q5NUL3 (FFAR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FFAR4
Synonyms:GPR120, GPR129, O3FAR1, PGR4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Note: Colocalized with ARRB2 following DHA treatment By similarity.

Tissue specificity

Abundant expression in the intestinal tract. Highly expressed in adipose tissue, small intestine and pancreas. Ref.2 Ref.7

Developmental stage

Expression detected in differentiated adipocytes but not in preadipocytes. Ref.7

Post-translational modification

Phosphorylated. FFA stimulation facilitates phosphorylation. Ref.8

Polymorphism

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

Miscellaneous

It has been shown that FFA alpha-linolenic acid stimulates secretion of glucagon-like peptide 1 (GLP-1) from the gastro-intestinal tract (Ref.2). 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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5NUL3-1)

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.
Note: Specific to human.
Isoform 2 (identifier: Q5NUL3-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 377377Free fatty acid receptor 4
PRO_0000069610

Regions

Topological domain1 – 4545Extracellular Potential
Transmembrane46 – 6621Helical; Name=1; Potential
Topological domain67 – 7711Cytoplasmic Potential
Transmembrane78 – 9821Helical; Name=2; Potential
Topological domain99 – 11214Extracellular Potential
Transmembrane113 – 13321Helical; Name=3; Potential
Topological domain134 – 15623Cytoplasmic Potential
Transmembrane157 – 17721Helical; Name=4; Potential
Topological domain178 – 20427Extracellular Potential
Transmembrane205 – 22521Helical; Name=5; Potential
Topological domain226 – 28459Cytoplasmic Potential
Transmembrane285 – 30521Helical; Name=6; Potential
Topological domain306 – 3116Extracellular Potential
Transmembrane312 – 33221Helical; Name=7; Potential
Topological domain333 – 37745Cytoplasmic Potential
Compositional bias67 – 715Poly-Arg

Amino acid modifications

Glycosylation211N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence233 – 24816Missing in isoform 2.
VSP_013684
Natural variant671R → C. Ref.2 Ref.9
Corresponds to variant rs61866610 [ dbSNP | Ensembl ].
VAR_067799
Natural variant2701R → H Polymorphism associated with increased risk of obesity. Ref.9
Corresponds to variant rs116454156 [ dbSNP | Ensembl ].
VAR_067800

Experimental info

Sequence conflict671Missing in AAP72126. Ref.1
Sequence conflict2741Q → H in BAD83368. Ref.2
Sequence conflict2971I → T in BAD83368. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 10, 2005. Version 2.
Checksum: 28BB8C3A939A7EFF

FASTA37742,241
        10         20         30         40         50         60 
MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI FAVSLLGNVC 

        70         80         90        100        110        120 
ALVLVARRRR RGATACLVLN LFCADLLFIS AIPLVLAVRW TEAWLLGPVA CHLLFYVMTL 

       130        140        150        160        170        180 
SGSVTILTLA AVSLERMVCI VHLQRGVRGP GRRARAVLLA LIWGYSAVAA LPLCVFFRVV 

       190        200        210        220        230        240 
PQRLPGADQE ISICTLIWPT IPGEISWDVS FVTLNFLVPG LVIVISYSKI LQTSEHLLDA 

       250        260        270        280        290        300 
RAVVTHSEIT KASRKRLTVS LAYSESHQIR VSQQDFRLFR TLFLLMVSFF IMWSPIIITI 

       310        320        330        340        350        360 
LLILIQNFKQ DLVIWPSLFF WVVAFTFANS ALNPILYNMT LCRNEWKKIF CCFWFPEKGA 

       370 
ILTDTSVKRN DLSIISG 

« Hide

Isoform 2 [UniParc].

Checksum: E90BD5D64D9E6E78
Show »

FASTA36140,494

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"The G protein-coupled receptor repertoires of human and mouse."
Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E., Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C., Bergmann J.E., Gaitanaris G.A.
Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 49-312 (ISOFORM 2).
[7]"The regulation of adipogenesis through GPR120."
Gotoh C., Hong Y.H., Iga T., Hishikawa D., Suzuki Y., Song S.H., Choi K.C., Adachi T., Hirasawa A., Tsujimoto G., Sasaki S., Roh S.G.
Biochem. Biophys. Res. Commun. 354:591-597(2007) [PubMed] [Europe PMC] [Abstract]
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]"Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human."
Ichimura A., Hirasawa A., Poulain-Godefroy O., Bonnefond A., Hara T., Yengo L., Kimura I., Leloire A., Liu N., Iida K., Choquet H., Besnard P., Lecoeur C., Vivequin S., Ayukawa K., Takeuchi M., Ozawa K., Tauber M. expand/collapse author list , Maffeis C., Morandi A., Buzzetti R., Elliott P., Pouta A., Jarvelin M.R., Korner A., Kiess W., Pigeyre M., Caiazzo R., Van Hul W., Van Gaal L., Horber F., Balkau B., Levy-Marchal C., Rouskas K., Kouvatsi A., Hebebrand J., Hinney A., Scherag A., Pattou F., Meyre D., Koshimizu T.A., Wolowczuk I., Tsujimoto G., Froguel P.
Nature 483:350-354(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BMIQ10, VARIANTS CYS-67 AND HIS-270, ASSOCIATION OF VARIANT HIS-270 WITH RISK OF OBESITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001182684.1. NM_001195755.1.
NP_859529.2. NM_181745.3.
UniGeneHs.661022.

3D structure databases

ProteinModelPortalQ5NUL3.
SMRQ5NUL3. Positions 38-366.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000360538.

Chemistry

BindingDBQ5NUL3.
ChEMBLCHEMBL5339.
GuidetoPHARMACOLOGY127.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ5NUL3.

Polymorphism databases

DMDM82581671.

Proteomic databases

PaxDbQ5NUL3.
PRIDEQ5NUL3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371481; ENSP00000360536; ENSG00000186188. [Q5NUL3-2]
ENST00000371483; ENSP00000360538; ENSG00000186188. [Q5NUL3-1]
GeneID338557.
KEGGhsa:338557.
UCSCuc010qnt.2. human. [Q5NUL3-1]
uc010qnu.2. human. [Q5NUL3-2]

Organism-specific databases

CTD338557.
GeneCardsGC10P095329.
HGNCHGNC:19061. FFAR4.
HPAHPA042563.
MIM607514. phenotype.
609044. gene.
neXtProtNX_Q5NUL3.
PharmGKBPA134924595.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241328.
HOVERGENHBG051775.
InParanoidQ5NUL3.
KOK08425.
OMAQITKASR.
OrthoDBEOG7PK900.
PhylomeDBQ5NUL3.
TreeFamTF336844.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ5NUL3.
CleanExHS_GPR120.
GenevestigatorQ5NUL3.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGPR120.
GenomeRNAi338557.
NextBio97032.
PROQ5NUL3.
SOURCESearch...

Entry information

Entry nameFFAR4_HUMAN
AccessionPrimary (citable) accession number: Q5NUL3
Secondary accession number(s): Q495H1 expand/collapse secondary AC list , Q5VY25, Q5VY26, Q7Z605, Q86SM7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: April 16, 2014
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries