Q5NUL3 (FFAR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FFAR4
Synonyms:	GPR120, GPR129, O3FAR1, PGR4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Lipid-binding
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	hormone secretion Inferred from electronic annotation. Source: Compara negative regulation of cytokine secretion Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB regulation of glucose transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	endocytic vesicle Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	fatty acid binding Inferred from sequence or structural similarity. Source: UniProtKB taste receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 377	377	Free fatty acid receptor 4		PRO_0000069610
Regions
	Topological domain	1 – 45	45	Extracellular Potential
	Transmembrane	46 – 66	21	Helical; Name=1; Potential
	Topological domain	67 – 77	11	Cytoplasmic Potential
	Transmembrane	78 – 98	21	Helical; Name=2; Potential
	Topological domain	99 – 112	14	Extracellular Potential
	Transmembrane	113 – 133	21	Helical; Name=3; Potential
	Topological domain	134 – 156	23	Cytoplasmic Potential
	Transmembrane	157 – 177	21	Helical; Name=4; Potential
	Topological domain	178 – 204	27	Extracellular Potential
	Transmembrane	205 – 225	21	Helical; Name=5; Potential
	Topological domain	226 – 284	59	Cytoplasmic Potential
	Transmembrane	285 – 305	21	Helical; Name=6; Potential
	Topological domain	306 – 311	6	Extracellular Potential
	Transmembrane	312 – 332	21	Helical; Name=7; Potential
	Topological domain	333 – 377	45	Cytoplasmic Potential
	Compositional bias	67 – 71	5	Poly-Arg
Amino acid modifications
	Glycosylation	21	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	233 – 248	16	Missing in isoform 2.		VSP_013684
	Natural variant	67	1	R → C. Ref.2 Ref.9 Corresponds to variant rs61866610 [ dbSNP | Ensembl ].		VAR_067799
	Natural variant	270	1	R → H Polymorphism associated with increased risk of obesity. Ref.9 Corresponds to variant rs116454156 [ dbSNP | Ensembl ].		VAR_067800
Experimental info
	Sequence conflict	67	1	Missing in AAP72126. Ref.1
	Sequence conflict	274	1	Q → H in BAD83368. Ref.2
	Sequence conflict	297	1	I → T in BAD83368. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: 28BB8C3A939A7EFF	FASTA	377	42,241
	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
	Isoform 2 [UniParc]. Checksum: E90BD5D64D9E6E78	FASTA	361	40,494
	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 LQITKASRKR 250 260 270 280 290 300 LTVSLAYSES HQIRVSQQDF RLFRTLFLLM VSFFIMWSPI IITILLILIQ NFKQDLVIWP 310 320 330 340 350 360 SLFFWVVAFT FANSALNPIL YNMTLCRNEW KKIFCCFWFP EKGAILTDTS VKRNDLSIIS G

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00376213. IPI00383963.
RefSeq	NP_001182684.1. NM_001195755.1. NP_859529.2. NM_181745.3.
UniGene	Hs.661022.
3D structure databases
ProteinModelPortal	Q5NUL3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000360538.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q5NUL3.
Polymorphism databases
DMDM	82581671.
Proteomic databases
PaxDb	Q5NUL3.
PRIDE	Q5NUL3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371481; ENSP00000360536; ENSG00000186188. ENST00000371483; ENSP00000360538; ENSG00000186188.
GeneID	338557.
KEGG	hsa:338557.
UCSC	uc010qnt.2. human. uc010qnu.2. human.
Organism-specific databases
CTD	338557.
GeneCards	GC10P095326.
HGNC	HGNC:19061. FFAR4.
HPA	HPA042563.
MIM	607514. phenotype. 609044. gene.
neXtProt	NX_Q5NUL3.
PharmGKB	PA134924595.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241328.
HOVERGEN	HBG051775.
InParanoid	Q5NUL3.
KO	K08425.
OMA	QITKASR.
PhylomeDB	Q5NUL3.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q5NUL3.
CleanEx	HS_GPR120.
Genevestigator	Q5NUL3.
GermOnline	ENSG00000186188. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q5NUL3.
ChEMBL	CHEMBL5339.
GenomeRNAi	338557.
NextBio	97032.
SOURCE	Search...

Entry information

Entry name

FFAR4_HUMAN

Accession

Primary (citable) accession number: Q5NUL3
Secondary accession number(s): Q495H1 , Q5VY25, Q5VY26, Q7Z605, Q86SM7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 10, 2005
Last modified:	May 1, 2013
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.