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Q5NUL3

- FFAR4_HUMAN

UniProt

Q5NUL3 - FFAR4_HUMAN

Protein

Free fatty acid receptor 4

Gene

FFAR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 95 (01 Oct 2014)
      Sequence version 2 (10 May 2005)
      Previous versions | rss
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    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

    1. fatty acid binding Source: UniProtKB
    2. taste receptor activity Source: Ensembl

    GO - Biological processi

    1. hormone secretion Source: Ensembl
    2. negative regulation of apoptotic process Source: UniProtKB
    3. negative regulation of cytokine secretion Source: UniProtKB
    4. negative regulation of inflammatory response Source: UniProtKB
    5. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    6. regulation of glucose transport Source: UniProtKB

    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: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:19061. FFAR4.

    Subcellular locationi

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

    GO - Cellular componenti

    1. endocytic vesicle Source: Ensembl
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    MIMi607514. phenotype.
    PharmGKBiPA134924595.

    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.
    GenevestigatoriQ5NUL3.

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4545ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini67 – 7711CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini99 – 11214ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini134 – 15623CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini178 – 20427ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini226 – 28459CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini306 – 3116ExtracellularSequence Analysis
    Topological domaini333 – 37745CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei46 – 6621Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei78 – 9821Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei113 – 13321Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei157 – 17721Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei205 – 22521Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei285 – 30521Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei312 – 33221Helical; Name=7Sequence AnalysisAdd
    BLAST

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

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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. Align

    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

    MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI    50
    FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFIS AIPLVLAVRW 100
    TEAWLLGPVA CHLLFYVMTL SGSVTILTLA AVSLERMVCI VHLQRGVRGP 150
    GRRARAVLLA LIWGYSAVAA LPLCVFFRVV PQRLPGADQE ISICTLIWPT 200
    IPGEISWDVS FVTLNFLVPG LVIVISYSKI LQTSEHLLDA RAVVTHSEIT 250
    KASRKRLTVS LAYSESHQIR VSQQDFRLFR TLFLLMVSFF IMWSPIIITI 300
    LLILIQNFKQ DLVIWPSLFF WVVAFTFANS ALNPILYNMT LCRNEWKKIF 350
    CCFWFPEKGA ILTDTSVKRN DLSIISG 377

    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:
    EMBL
    GenBank
    DDBJ
    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]

    Polymorphism databases

    DMDMi82581671.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS31248.1. [Q5NUL3-1 ]
    CCDS55720.1. [Q5NUL3-2 ]
    RefSeqi NP_001182684.1. NM_001195755.1. [Q5NUL3-2 ]
    NP_859529.2. NM_181745.3. [Q5NUL3-1 ]
    UniGenei Hs.661022.

    3D structure databases

    ProteinModelPortali Q5NUL3.
    SMRi Q5NUL3. Positions 37-337.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000360538.

    Chemistry

    BindingDBi Q5NUL3.
    ChEMBLi CHEMBL5339.
    GuidetoPHARMACOLOGYi 127.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q5NUL3.

    Polymorphism databases

    DMDMi 82581671.

    Proteomic databases

    PaxDbi Q5NUL3.
    PRIDEi Q5NUL3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000371481 ; ENSP00000360536 ; ENSG00000186188 . [Q5NUL3-2 ]
    ENST00000371483 ; ENSP00000360538 ; ENSG00000186188 . [Q5NUL3-1 ]
    GeneIDi 338557.
    KEGGi hsa:338557.
    UCSCi uc010qnt.2. human. [Q5NUL3-1 ]
    uc010qnu.2. human. [Q5NUL3-2 ]

    Organism-specific databases

    CTDi 338557.
    GeneCardsi GC10P095329.
    HGNCi HGNC:19061. FFAR4.
    HPAi HPA042563.
    MIMi 607514. phenotype.
    609044. gene.
    neXtProti NX_Q5NUL3.
    PharmGKBi PA134924595.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG241328.
    HOVERGENi HBG051775.
    InParanoidi Q5NUL3.
    KOi K08425.
    OMAi YSKILQI.
    OrthoDBi EOG7PK900.
    PhylomeDBi Q5NUL3.
    TreeFami TF336844.

    Enzyme and pathway databases

    Reactomei REACT_21268. Free fatty acid receptors.
    REACT_24019. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

    Miscellaneous databases

    GeneWikii GPR120.
    GenomeRNAii 338557.
    NextBioi 97032.
    PROi Q5NUL3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q5NUL3.
    CleanExi HS_GPR120.
    Genevestigatori Q5NUL3.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 95 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