Target has curated data in GtoImmuPdb
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Agonists
- Antagonists
- Allosteric Modulators
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Immuno Process Associations
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 330 | 19q13.12 | FFAR2 | free fatty acid receptor 2 | 21 |
| Mouse | 7 | 330 | 7 B1 | Ffar2 | free fatty acid receptor 2 | 23 |
| Rat | 7 | 330 | 1q21 | Ffar2 | free fatty acid receptor 2 | 10 |
| Previous and Unofficial Names |
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| FFA2R | GPCR3 | GPR43 [21] | G protein-coupled receptor 43 | |
| Database Links |
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| Specialist databases | |
| GPCRdb | ffar2_human (Hs), ffar2_mouse (Mm) |
| Other databases | |
| Alphafold | O15552 (Hs), Q8VCK6 (Mm), Q76EI6 (Rn) |
| ChEMBL Target | CHEMBL5493 (Hs), CHEMBL3309047 (Mm), CHEMBL3309100 (Rn) |
| Ensembl Gene | ENSG00000126262 (Hs), ENSMUSG00000051314 (Mm), ENSRNOG00000021021 (Rn) |
| Entrez Gene | 2867 (Hs), 233079 (Mm), 292794 (Rn) |
| Human Protein Atlas | ENSG00000126262 (Hs) |
| KEGG Gene | hsa:2867 (Hs), mmu:233079 (Mm), rno:292794 (Rn) |
| OMIM | 603823 (Hs) |
| Pharos | O15552 (Hs) |
| RefSeq Nucleotide | NM_005306 (Hs), NM_146187 (Mm), NM_001005877 (Rn) |
| RefSeq Protein | NP_005297 (Hs), NP_666299 (Mm), NP_001005877 (Rn) |
| UniProtKB | O15552 (Hs), Q8VCK6 (Mm), Q76EI6 (Rn) |
| Wikipedia | FFAR2 (Hs) |
| Natural/Endogenous Ligands |
| acetic acid |
| butyric acid |
| 1-methylcyclopropanecarboxylic acid |
| propanoic acid |
| trans-2-methylcrotonic acid |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| A series of short chain fatty acids with varying degrees of selectivity for FFA2 over FFA3 have been reported [22]. It has been noted that there are differences in the potency of short chain fatty acids at FFA2 receptors from different species [9]. For example, the bovine varient of FFA2 is activated by longer chain fatty acids, such as caproic acid (C6) and enathic acid (C7) compared to human FFA2 [7]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| To date no compounds that act as antagonists at FFA2 have been reported in the peer reviewed literature but FFA2 antagonists have been described in patent applications [28]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Allosteric Modulator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Further allosteric modulators based on the structure of AMG7703 have been reported [25,31] but without any significant increase in potency. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932). In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [32]. These discoveries help to identify FFAR2 and intestinal microbiota as critical players that underly cholera toxin's adjuvant activity, and have the potential to drive the development of more effective immunisation adjuvants. |
| Cell Type Associations | ||||||||
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| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| References: 2,13,18 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gi/Go family | Adenylyl cyclase inhibition |
| References: 2,13,18 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| FFA2 expression has been shown to be down-regulated in human colorectal adenocarcinomas and in human colon cancer cell lines [26]. | ||||||||
| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Functions Comments | ||||||||
| A general function of FFA2 in nutrient sensing in the gut to maintain energy homoeostatsis has been suggested [20]. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| FFA3 is found to be upregulated in FFA2 knockout mice suggesting a compensatory mechanism may be involved with the two short chain fatty acid receptors [1]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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References
1. Bjursell M, Admyre T, Göransson M, Marley AE, Smith DM, Oscarsson J, Bohlooly-Y M. (2011) Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am J Physiol Endocrinol Metab, 300 (1): E211-20. [PMID:20959533]
2. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ et al.. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem, 278 (13): 11312-9. [PMID:12496283]
3. Brown AJ, Jupe S, Briscoe CP. (2005) A family of fatty acid binding receptors. DNA Cell Biol, 24 (1): 54-61. [PMID:15684720]
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7. Hudson BD, Christiansen E, Tikhonova IG, Grundmann M, Kostenis E, Adams DR, Ulven T, Milligan G. (2012) Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs. FASEB J, 26 (12): 4951-65. [PMID:22919070]
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25. Smith NJ, Ward RJ, Stoddart LA, Hudson BD, Kostenis E, Ulven T, Morris JC, Tränkle C, Tikhonova IG, Adams DR et al.. (2011) Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator. Mol Pharmacol, 80 (1): 163-73. [PMID:21498659]
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