FFAR2_HUMAN
ID FFAR2_HUMAN Reviewed; 330 AA.
AC O15552; B0M0J9; Q4VAZ3; Q4VAZ5; Q4VBL5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Free fatty acid receptor 2;
DE AltName: Full=G-protein coupled receptor 43;
GN Name=FFAR2; Synonyms=FFA2, GPCR43, GPR43;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9344866; DOI=10.1006/bbrc.1997.7513;
RA Sawzdargo M., George S.R., Nguyen T., Xu S., Kolakowski L.F. Jr.,
RA O'Dowd B.F.;
RT "A cluster of four novel human G protein-coupled receptor genes occurring
RT in close proximity to CD22 gene on chromosome 19q13.1.";
RL Biochem. Biophys. Res. Commun. 239:543-547(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12684041; DOI=10.1016/s0006-291x(03)00488-1;
RA Nilsson N.E., Kotarsky K., Owman C., Olde B.;
RT "Identification of a free fatty acid receptor, FFA2R, expressed on
RT leukocytes and activated by short-chain fatty acids.";
RL Biochem. Biophys. Res. Commun. 303:1047-1052(2003).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12496283; DOI=10.1074/jbc.m211609200;
RA Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M.M., Tcheang L.,
RA Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J.,
RA Pike N.B., Strum J.C., Steplewski K.M., Murdock P.R., Holder J.C.,
RA Marshall F.H., Szekeres P.G., Wilson S., Ignar D.M., Foord S.M., Wise A.,
RA Dowell S.J.;
RT "The orphan G protein-coupled receptors GPR41 and GPR43 are activated by
RT propionate and other short chain carboxylic acids.";
RL J. Biol. Chem. 278:11312-11319(2003).
RN [7]
RP FUNCTION.
RX PubMed=12711604; DOI=10.1074/jbc.m301403200;
RA Le Poul E., Loison C., Struyf S., Springael J.Y., Lannoy V., Decobecq M.E.,
RA Brezillon S., Dupriez V., Vassart G., Van Damme J., Parmentier M.,
RA Detheux M.;
RT "Functional characterization of human receptors for short chain fatty acids
RT and their role in polymorphonuclear cell activation.";
RL J. Biol. Chem. 278:25481-25489(2003).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-140; ARG-180;
RP HIS-242 AND ARG-255.
RX PubMed=18801738; DOI=10.1074/jbc.m805601200;
RA Stoddart L.A., Smith N.J., Jenkins L., Brown A.J., Milligan G.;
RT "Conserved polar residues in transmembrane domains V, VI, and VII of free
RT fatty acid receptor 2 and free fatty acid receptor 3 are required for the
RT binding and function of short chain fatty acids.";
RL J. Biol. Chem. 283:32913-32924(2008).
RN [9]
RP MUTAGENESIS OF GLU-106; TYR-108; ARG-180 AND ARG-255.
RX PubMed=20837008; DOI=10.1016/j.febslet.2010.09.007;
RA Swaminath G., Jaeckel P., Guo Q., Cardozo M., Weiszmann J., Lindberg R.,
RA Wang Y., Schwandner R., Li Y.;
RT "Allosteric rescuing of loss-of-function FFAR2 mutations.";
RL FEBS Lett. 584:4208-4214(2010).
RN [10]
RP FUNCTION, AND INTERACTION WITH FCN1.
RX PubMed=21037097; DOI=10.4049/jimmunol.1001225;
RA Zhang J., Yang L., Ang Z., Yoong S.L., Tran T.T., Anand G.S., Tan N.S.,
RA Ho B., Ding J.L.;
RT "Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled
RT receptor 43 and cross talks with plasma C-reactive protein to mediate
RT immune signaling and regulate host defense.";
RL J. Immunol. 185:6899-6910(2010).
RN [11]
RP MUTAGENESIS OF TYR-90; ASN-239 AND HIS-242.
RX PubMed=21216233; DOI=10.1016/j.bbrc.2010.12.139;
RA Swaminath G., Jaeckel P., Guo Q., Cardozo M., Weiszmann J., Lindberg R.,
RA Wang Y., Schwandner R., Li Y.;
RT "Mutational analysis of G-protein coupled receptor--FFA2.";
RL Biochem. Biophys. Res. Commun. 405:122-127(2011).
RN [12]
RP MUTAGENESIS OF GLY-159.
RX PubMed=23066016; DOI=10.1074/jbc.m112.396259;
RA Hudson B.D., Tikhonova I.G., Pandey S.K., Ulven T., Milligan G.;
RT "Extracellular ionic locks determine variation in constitutive activity and
RT ligand potency between species orthologs of the free fatty acid receptors
RT FFA2 and FFA3.";
RL J. Biol. Chem. 287:41195-41209(2012).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF TYR-90; HIS-140; GLN-148; TYR-165; ARG-180;
RP TYR-238; HIS-242 AND ARG-255.
RX PubMed=23589301; DOI=10.1074/jbc.m113.455337;
RA Hudson B.D., Due-Hansen M.E., Christiansen E., Hansen A.M., Mackenzie A.E.,
RA Murdoch H., Pandey S.K., Ward R.J., Marquez R., Tikhonova I.G., Ulven T.,
RA Milligan G.;
RT "Defining the molecular basis for the first potent and selective
RT orthosteric agonists of the FFA2 free fatty acid receptor.";
RL J. Biol. Chem. 288:17296-17312(2013).
CC -!- FUNCTION: G protein-coupled receptor that is activated by a major
CC product of dietary fiber digestion, the short chain fatty acids
CC (SCFAs), and that plays a role in the regulation of whole-body energy
CC homeostasis and in intestinal immunity. In omnivorous mammals, the
CC short chain fatty acids acetate, propionate and butyrate are produced
CC primarily by the gut microbiome that metabolizes dietary fibers. SCFAs
CC serve as a source of energy but also act as signaling molecules. That G
CC protein-coupled receptor is probably coupled to the pertussis toxin-
CC sensitive, G(i/o)-alpha family of G proteins but also to the Gq family
CC (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation
CC results in the formation of inositol 1,4,5-trisphosphate, the
CC mobilization of intracellular calcium, the phosphorylation of the
CC MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular
CC cAMP accumulation. May play a role in glucose homeostasis by regulating
CC the secretion of GLP-1, in response to short-chain fatty acids
CC accumulating in the intestine. May also regulate the production of
CC LEP/Leptin, a hormone acting on the central nervous system to inhibit
CC food intake. Finally, may also regulate whole-body energy homeostasis
CC through adipogenesis regulating both differentiation and lipid storage
CC of adipocytes. In parallel to its role in energy homeostasis, may also
CC mediate the activation of the inflammatory and immune responses by SCFA
CC in the intestine, regulating the rapid production of chemokines and
CC cytokines. May also play a role in the resolution of the inflammatory
CC response and control chemotaxis in neutrophils. In addition to SCFAs,
CC may also be activated by the extracellular lectin FCN1 in a process
CC leading to activation of monocytes and inducing the secretion of
CC interleukin-8/IL-8 in response to the presence of microbes
CC (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6
CC carbons, the most potent activators are probably acetate, propionate
CC and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-
CC independent constitutive G protein-coupled receptor activity
CC (PubMed:23066016). {ECO:0000269|PubMed:12496283,
CC ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:12711604,
CC ECO:0000269|PubMed:18801738, ECO:0000269|PubMed:21037097,
CC ECO:0000269|PubMed:23066016, ECO:0000269|PubMed:23589301}.
CC -!- SUBUNIT: Interacts with FCN1 (via Fibrinogen C-terminal domain).
CC {ECO:0000269|PubMed:21037097}.
CC -!- INTERACTION:
CC O15552; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-2833872, EBI-1754287;
CC O15552; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-2833872, EBI-11522760;
CC O15552; P20292: ALOX5AP; NbExp=3; IntAct=EBI-2833872, EBI-3904621;
CC O15552; P05090: APOD; NbExp=3; IntAct=EBI-2833872, EBI-715495;
CC O15552; Q9HD20-3: ATP13A1; NbExp=3; IntAct=EBI-2833872, EBI-12069500;
CC O15552; P27449: ATP6V0C; NbExp=3; IntAct=EBI-2833872, EBI-721179;
CC O15552; O95393: BMP10; NbExp=3; IntAct=EBI-2833872, EBI-3922513;
CC O15552; Q12983: BNIP3; NbExp=3; IntAct=EBI-2833872, EBI-749464;
CC O15552; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-2833872, EBI-8648738;
CC O15552; Q96F05: C11orf24; NbExp=3; IntAct=EBI-2833872, EBI-2836238;
CC O15552; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-2833872, EBI-12003442;
CC O15552; Q06432: CACNG1; NbExp=3; IntAct=EBI-2833872, EBI-9686780;
CC O15552; P27352: CBLIF; NbExp=3; IntAct=EBI-2833872, EBI-3953638;
CC O15552; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-2833872, EBI-9083477;
CC O15552; P27701: CD82; NbExp=3; IntAct=EBI-2833872, EBI-682379;
CC O15552; O14735: CDIPT; NbExp=3; IntAct=EBI-2833872, EBI-358858;
CC O15552; Q9BXR6: CFHR5; NbExp=3; IntAct=EBI-2833872, EBI-11579371;
CC O15552; Q99675: CGRRF1; NbExp=3; IntAct=EBI-2833872, EBI-2130213;
CC O15552; O14493: CLDN4; NbExp=3; IntAct=EBI-2833872, EBI-9316372;
CC O15552; Q8NHS1: CLDND2; NbExp=3; IntAct=EBI-2833872, EBI-11959453;
CC O15552; Q8NC01: CLEC1A; NbExp=3; IntAct=EBI-2833872, EBI-11996768;
CC O15552; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-2833872, EBI-11522780;
CC O15552; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-2833872, EBI-2807956;
CC O15552; O95406: CNIH1; NbExp=3; IntAct=EBI-2833872, EBI-12172273;
CC O15552; P29400-2: COL4A5; NbExp=3; IntAct=EBI-2833872, EBI-12211159;
CC O15552; Q07325: CXCL9; NbExp=3; IntAct=EBI-2833872, EBI-3911467;
CC O15552; Q8NBI2: CYB561A3; NbExp=3; IntAct=EBI-2833872, EBI-10269179;
CC O15552; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-2833872, EBI-398977;
CC O15552; P56851: EDDM3B; NbExp=3; IntAct=EBI-2833872, EBI-10215665;
CC O15552; P54849: EMP1; NbExp=3; IntAct=EBI-2833872, EBI-4319440;
CC O15552; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-2833872, EBI-711490;
CC O15552; O75063: FAM20B; NbExp=3; IntAct=EBI-2833872, EBI-11090967;
CC O15552; Q92520: FAM3C; NbExp=3; IntAct=EBI-2833872, EBI-2876774;
CC O15552; Q96IV6: FAXDC2; NbExp=3; IntAct=EBI-2833872, EBI-12142299;
CC O15552; PRO_0000009136 [O00602]: FCN1; NbExp=7; IntAct=EBI-2833872, EBI-11784425;
CC O15552; Q9Y3D6: FIS1; NbExp=3; IntAct=EBI-2833872, EBI-3385283;
CC O15552; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-2833872, EBI-12175685;
CC O15552; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-2833872, EBI-713304;
CC O15552; O75084: FZD7; NbExp=3; IntAct=EBI-2833872, EBI-746917;
CC O15552; Q8N3T1: GALNT15; NbExp=3; IntAct=EBI-2833872, EBI-3925203;
CC O15552; P29033: GJB2; NbExp=3; IntAct=EBI-2833872, EBI-3905204;
CC O15552; O60883: GPR37L1; NbExp=3; IntAct=EBI-2833872, EBI-2927498;
CC O15552; Q02747: GUCA2A; NbExp=3; IntAct=EBI-2833872, EBI-12244272;
CC O15552; P02724: GYPA; NbExp=3; IntAct=EBI-2833872, EBI-702665;
CC O15552; Q01628: IFITM3; NbExp=3; IntAct=EBI-2833872, EBI-7932862;
CC O15552; P04264: KRT1; NbExp=3; IntAct=EBI-2833872, EBI-298429;
CC O15552; Q86UP2-3: KTN1; NbExp=3; IntAct=EBI-2833872, EBI-12007212;
CC O15552; Q15012: LAPTM4A; NbExp=3; IntAct=EBI-2833872, EBI-723416;
CC O15552; O43561-2: LAT; NbExp=3; IntAct=EBI-2833872, EBI-8070286;
CC O15552; O95214: LEPROTL1; NbExp=3; IntAct=EBI-2833872, EBI-750776;
CC O15552; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-2833872, EBI-2820517;
CC O15552; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-2833872, EBI-12033434;
CC O15552; Q13021: MALL; NbExp=3; IntAct=EBI-2833872, EBI-750078;
CC O15552; Q6N075: MFSD5; NbExp=3; IntAct=EBI-2833872, EBI-3920969;
CC O15552; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-2833872, EBI-12070086;
CC O15552; Q9UHE5: NAT8; NbExp=3; IntAct=EBI-2833872, EBI-2863634;
CC O15552; Q0D2K0: NIPAL4; NbExp=3; IntAct=EBI-2833872, EBI-9550165;
CC O15552; Q16617: NKG7; NbExp=3; IntAct=EBI-2833872, EBI-3919611;
CC O15552; Q8IXM6: NRM; NbExp=3; IntAct=EBI-2833872, EBI-10262547;
CC O15552; P42857: NSG1; NbExp=3; IntAct=EBI-2833872, EBI-6380741;
CC O15552; Q8NH19: OR10AG1; NbExp=3; IntAct=EBI-2833872, EBI-13339917;
CC O15552; Q9Y5Y5: PEX16; NbExp=3; IntAct=EBI-2833872, EBI-981985;
CC O15552; P60201-2: PLP1; NbExp=3; IntAct=EBI-2833872, EBI-12188331;
CC O15552; Q01453: PMP22; NbExp=3; IntAct=EBI-2833872, EBI-2845982;
CC O15552; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-2833872, EBI-8652812;
CC O15552; Q9NS64: RPRM; NbExp=3; IntAct=EBI-2833872, EBI-1052363;
CC O15552; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-2833872, EBI-10244780;
CC O15552; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-2833872, EBI-8636004;
CC O15552; Q9NTJ5: SACM1L; NbExp=3; IntAct=EBI-2833872, EBI-3917235;
CC O15552; O95968: SCGB1D1; NbExp=3; IntAct=EBI-2833872, EBI-12825395;
CC O15552; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-2833872, EBI-9679163;
CC O15552; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-2833872, EBI-8644112;
CC O15552; Q969S0: SLC35B4; NbExp=3; IntAct=EBI-2833872, EBI-10281213;
CC O15552; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-2833872, EBI-17295964;
CC O15552; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-2833872, EBI-13389236;
CC O15552; Q9H2H9: SLC38A1; NbExp=3; IntAct=EBI-2833872, EBI-9978441;
CC O15552; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-2833872, EBI-2823239;
CC O15552; Q8IVJ1: SLC41A1; NbExp=3; IntAct=EBI-2833872, EBI-12266234;
CC O15552; Q0VAQ4: SMAGP; NbExp=3; IntAct=EBI-2833872, EBI-10226799;
CC O15552; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-2833872, EBI-8640191;
CC O15552; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-2833872, EBI-12188413;
CC O15552; P0DN84: STRIT1; NbExp=3; IntAct=EBI-2833872, EBI-12200293;
CC O15552; Q9UNK0: STX8; NbExp=3; IntAct=EBI-2833872, EBI-727240;
CC O15552; Q9H7V2: SYNDIG1; NbExp=3; IntAct=EBI-2833872, EBI-726331;
CC O15552; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-2833872, EBI-10329860;
CC O15552; P48230: TM4SF4; NbExp=3; IntAct=EBI-2833872, EBI-8650934;
CC O15552; P17152: TMEM11; NbExp=3; IntAct=EBI-2833872, EBI-723946;
CC O15552; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-2833872, EBI-10171534;
CC O15552; Q7Z5S9: TMEM144; NbExp=3; IntAct=EBI-2833872, EBI-12876358;
CC O15552; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-2833872, EBI-348587;
CC O15552; Q969S6: TMEM203; NbExp=3; IntAct=EBI-2833872, EBI-12274070;
CC O15552; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-2833872, EBI-11528917;
CC O15552; E9PQX1: TMEM262; NbExp=3; IntAct=EBI-2833872, EBI-17180389;
CC O15552; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-2833872, EBI-2852148;
CC O15552; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-2833872, EBI-12015604;
CC O15552; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-2833872, EBI-12111910;
CC O15552; P01375: TNF; NbExp=3; IntAct=EBI-2833872, EBI-359977;
CC O15552; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-2833872, EBI-12195249;
CC O15552; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-2833872, EBI-10243654;
CC O15552; Q53HI1: UNC50; NbExp=3; IntAct=EBI-2833872, EBI-7601760;
CC O15552; O75841: UPK1B; NbExp=3; IntAct=EBI-2833872, EBI-12237619;
CC O15552; O95070: YIF1A; NbExp=3; IntAct=EBI-2833872, EBI-2799703;
CC O15552; Q9BWQ6: YIPF2; NbExp=3; IntAct=EBI-2833872, EBI-751204;
CC O15552; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-2833872, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18801738};
CC Multi-pass membrane protein {ECO:0000269|PubMed:18801738}.
CC -!- TISSUE SPECIFICITY: Expressed at relatively high levels in peripheral
CC blood leukocytes and, to lesser extent, in spleen.
CC {ECO:0000269|PubMed:12496283, ECO:0000269|PubMed:12684041}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF024690; AAB86713.1; -; Genomic_DNA.
DR EMBL; AC002511; AAB67886.1; -; Genomic_DNA.
DR EMBL; EU432114; ABY87913.1; -; Genomic_DNA.
DR EMBL; BC095535; AAH95535.1; -; mRNA.
DR EMBL; BC096198; AAH96198.1; -; mRNA.
DR EMBL; BC096199; AAH96199.1; -; mRNA.
DR EMBL; BC096200; AAH96200.1; -; mRNA.
DR EMBL; BC096201; AAH96201.1; -; mRNA.
DR CCDS; CCDS12461.1; -.
DR PIR; JC5717; JC5717.
DR RefSeq; NP_005297.1; NM_005306.2.
DR RefSeq; XP_016882198.1; XM_017026709.1.
DR RefSeq; XP_016882199.1; XM_017026710.1.
DR RefSeq; XP_016882200.1; XM_017026711.1.
DR AlphaFoldDB; O15552; -.
DR SMR; O15552; -.
DR BioGRID; 109125; 110.
DR IntAct; O15552; 111.
DR STRING; 9606.ENSP00000473159; -.
DR BindingDB; O15552; -.
DR ChEMBL; CHEMBL5493; -.
DR DrugCentral; O15552; -.
DR GuidetoPHARMACOLOGY; 226; -.
DR SwissLipids; SLP:000001558; -.
DR GlyGen; O15552; 2 sites.
DR iPTMnet; O15552; -.
DR PhosphoSitePlus; O15552; -.
DR BioMuta; FFAR2; -.
DR PaxDb; O15552; -.
DR PeptideAtlas; O15552; -.
DR PRIDE; O15552; -.
DR ProteomicsDB; 48754; -.
DR Antibodypedia; 15916; 349 antibodies from 31 providers.
DR DNASU; 2867; -.
DR Ensembl; ENST00000246549.2; ENSP00000246549.2; ENSG00000126262.5.
DR Ensembl; ENST00000599180.3; ENSP00000473159.1; ENSG00000126262.5.
DR GeneID; 2867; -.
DR KEGG; hsa:2867; -.
DR MANE-Select; ENST00000599180.3; ENSP00000473159.1; NM_001370087.1; NP_001357016.1.
DR UCSC; uc010eea.4; human.
DR CTD; 2867; -.
DR DisGeNET; 2867; -.
DR GeneCards; FFAR2; -.
DR HGNC; HGNC:4501; FFAR2.
DR HPA; ENSG00000126262; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 603823; gene.
DR neXtProt; NX_O15552; -.
DR OpenTargets; ENSG00000126262; -.
DR PharmGKB; PA28890; -.
DR VEuPathDB; HostDB:ENSG00000126262; -.
DR eggNOG; ENOG502QQGM; Eukaryota.
DR GeneTree; ENSGT00990000203527; -.
DR HOGENOM; CLU_009579_8_4_1; -.
DR InParanoid; O15552; -.
DR OMA; ITIFCYW; -.
DR OrthoDB; 1129026at2759; -.
DR PhylomeDB; O15552; -.
DR TreeFam; TF350010; -.
DR PathwayCommons; O15552; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-444209; Free fatty acid receptors.
DR SignaLink; O15552; -.
DR SIGNOR; O15552; -.
DR BioGRID-ORCS; 2867; 12 hits in 1072 CRISPR screens.
DR GenomeRNAi; 2867; -.
DR Pharos; O15552; Tchem.
DR PRO; PR:O15552; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O15552; protein.
DR Bgee; ENSG00000126262; Expressed in blood and 97 other tissues.
DR ExpressionAtlas; O15552; baseline and differential.
DR Genevisible; O15552; HS.
DR GO; GO:0042995; C:cell projection; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0002752; P:cell surface pattern recognition receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; ISS:UniProtKB.
DR GO; GO:0002385; P:mucosal immune response; ISS:UniProtKB.
DR GO; GO:0002879; P:positive regulation of acute inflammatory response to non-antigenic stimulus; ISS:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0002673; P:regulation of acute inflammatory response; ISS:UniProtKB.
DR GO; GO:0090276; P:regulation of peptide hormone secretion; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR013312; GPR40-rel_orph.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01904; GPR40FAMILY.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; G-protein coupled receptor; Glycoprotein; Immunity;
KW Inflammatory response; Lipid-binding; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..330
FT /note="Free fatty acid receptor 2"
FT /id="PRO_0000069571"
FT TOPO_DOM 1..12
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..41
FT /note="Cytoplasmic"
FT TRANSMEM 42..62
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..84
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 148..173
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 241..255
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 299..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 211
FT /note="L -> H (in dbSNP:rs409093)"
FT /id="VAR_011861"
FT MUTAGEN 90
FT /note="Y->A: Partial loss of propionate-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:21216233,
FT ECO:0000269|PubMed:23589301"
FT MUTAGEN 90
FT /note="Y->W: Complete loss of acetate-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:21216233,
FT ECO:0000269|PubMed:23589301"
FT MUTAGEN 106
FT /note="E->A: Partial loss of SCFA-induced G protein-coupled
FT receptor activity."
FT /evidence="ECO:0000269|PubMed:20837008"
FT MUTAGEN 108
FT /note="Y->A: Complete loss of SCFA-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:20837008"
FT MUTAGEN 140
FT /note="H->A: Partial loss of SCFA-induced G protein-coupled
FT receptor activity."
FT /evidence="ECO:0000269|PubMed:18801738,
FT ECO:0000269|PubMed:23589301"
FT MUTAGEN 148
FT /note="Q->A: No effect on SCFA-induced G protein-coupled
FT receptor activity."
FT /evidence="ECO:0000269|PubMed:23589301"
FT MUTAGEN 148
FT /note="Q->E: Partial loss of SCFA-induced G protein-coupled
FT receptor activity."
FT /evidence="ECO:0000269|PubMed:23589301"
FT MUTAGEN 159
FT /note="G->E: Partial loss of SCFA-independent constitutive
FT G protein-coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:23066016"
FT MUTAGEN 165
FT /note="Y->A: Partial loss of propionate-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:23589301"
FT MUTAGEN 180
FT /note="R->A,K,L,S: Complete loss of SCFA-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:18801738,
FT ECO:0000269|PubMed:20837008, ECO:0000269|PubMed:23589301"
FT MUTAGEN 238
FT /note="Y->A: Partial loss of propionate-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:23589301"
FT MUTAGEN 239
FT /note="N->A: Complete loss of acetate-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:21216233"
FT MUTAGEN 242
FT /note="H->A,F: Complete loss of SCFA-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:18801738,
FT ECO:0000269|PubMed:21216233, ECO:0000269|PubMed:23589301"
FT MUTAGEN 255
FT /note="R->A: Complete loss of SCFA-induced G protein-
FT coupled receptor activity."
FT /evidence="ECO:0000269|PubMed:18801738,
FT ECO:0000269|PubMed:20837008, ECO:0000269|PubMed:23589301"
FT CONFLICT 227
FT /note="T -> M (in Ref. 4; AAH96201)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37144 MW; F4A8AC6AFBDF1E90 CRC64;
MLPDWKSSLI LMAYIIIFLT GLPANLLALR AFVGRIRQPQ PAPVHILLLS LTLADLLLLL
LLPFKIIEAA SNFRWYLPKV VCALTSFGFY SSIYCSTWLL AGISIERYLG VAFPVQYKLS
RRPLYGVIAA LVAWVMSFGH CTIVIIVQYL NTTEQVRSGN EITCYENFTD NQLDVVLPVR
LELCLVLFFI PMAVTIFCYW RFVWIMLSQP LVGAQRRRRA VGLAVVTLLN FLVCFGPYNV
SHLVGYHQRK SPWWRSIAVV FSSLNASLDP LLFYFSSSVV RRAFGRGLQV LRNQGSSLLG
RRGKDTAEGT NEDRGVGQGE GMPSSDFTTE
