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 | 346 | 19q13.12 | FFAR3 | free fatty acid receptor 3 | 14 |
| Mouse | 7 | 319 | 7 B1 | Ffar3 | free fatty acid receptor 3 | 8 |
| Rat | 7 | 319 | 1q21 | Ffar3 | free fatty acid receptor 3 | 2 |
| Previous and Unofficial Names |
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| FFA3R | GPR41 [14] | LSSIG [17] | G protein-coupled receptor 41 | GPCR41 | |
| Database Links |
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| Specialist databases | |
| GPCRdb | ffar3_human (Hs), ffar3_mouse (Mm), ffar3_rat (Rn) |
| Other databases | |
| Alphafold | O14843 (Hs), Q3UFD7 (Mm), B2GV46 (Rn) |
| ChEMBL Target | CHEMBL5201 (Hs), CHEMBL3309101 (Mm), CHEMBL3886125 (Rn) |
| Ensembl Gene | ENSG00000185897 (Hs), ENSMUSG00000019429 (Mm), ENSRNOG00000037467 (Rn) |
| Entrez Gene | 2865 (Hs), 233080 (Mm), 365228 (Rn) |
| Human Protein Atlas | ENSG00000185897 (Hs) |
| KEGG Gene | hsa:2865 (Hs), mmu:233080 (Mm), rno:365228 (Rn) |
| OMIM | 603821 (Hs) |
| Pharos | O14843 (Hs) |
| RefSeq Nucleotide | NM_005304 (Hs), NM_001033316 (Mm), NM_001108912 (Rn) |
| RefSeq Protein | NP_005295 (Hs), NP_001028488 (Mm), NP_001102382 (Rn) |
| UniProtKB | O14843 (Hs), Q3UFD7 (Mm), B2GV46 (Rn) |
| Wikipedia | FFAR3 (Hs) |
| Natural/Endogenous Ligands |
| butyric acid |
| 1-methylcyclopropanecarboxylic acid |
| propanoic 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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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| A series of short chain fatty acids with varying degrees of selectivity for FFA3 over FFA2 have been reported [15]. Species orthologs of FFA3 have been found to have different rank orders of potencies for short chain fatty acids compared ot the human receptor [7]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist Comments | ||
| To date the only reported antagonist for FFA3 is β-hydroxybutyrate [10]. In this study the short-chain fatty acid propionate promoted sympathetic outflow via FFA3, whereas the ketone body β-hydroxybutyrate (which can be present in the circulation as a result of starvation or diabetes) antagonized FFA3, thus suppressing sympathetic nervous system activity. This is proposed as a mechanism whereby short-chain fatty acids and ketone bodies are able to directly regulate sympathetic nervous system activity and thereby control body energy expenditure and maintain metabolic homeostasis. |
| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Allosteric Modulator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| To date no compounds that act as allosteric modulators at FFA3 have been reported in the peer reviewed literature, but FFA3 allosteric modulators have been described in patent applications [21]. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [4], however do date its main physiological function seems to be in metabolic regulation [19]. |
| Cell Type Associations | ||||
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| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gi/Go family | Adenylyl cyclase inhibition |
| References: 23 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Expression of FFA3 in adipose tissue is a contentious issue, with some studies detecting expression in adipose tissue [3,23] and others failing to find any FFA3 expression [5,24]. FFA3 expression has been described in bovine rumen epithelium but not islet of Langerhans cells [22]. |
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| 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 FFA3 in nutrient sensing in the gut to maintain energy homoeostatsis has been suggested [12]. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Expression of FFA2 is found to be reduced in FFA3 knockout mice [24] which may hamper efforts to separate the physiological function of the two short chain fatty acids receptors. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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References
1. Bellahcene M, O'Dowd JF, Wargent ET, Zaibi MS, Hislop DC, Ngala RA, Smith DM, Cawthorne MA, Stocker CJ, Arch JR. (2013) Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content. Br J Nutr, 109 (10): 1755-64. [PMID:23110765]
2. Bonini JA, Anderson SM, Steiner DF. (1997) Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem Biophys Res Commun, 234 (1): 190-3. [PMID:9168987]
3. 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]
4. Brown AJ, Jupe S, Briscoe CP. (2005) A family of fatty acid binding receptors. DNA Cell Biol, 24 (1): 54-61. [PMID:15684720]
5. Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, Choi KC, Feng DD, Chen C, Lee HG et al.. (2005) Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology, 146 (12): 5092-9. [PMID:16123168]
6. Hudson BD, Christiansen E, Murdoch H, Jenkins L, Hansen AH, Madsen O, Ulven T, Milligan G. (2014) Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands. Mol Pharmacol, 86 (2): 200-10. [PMID:24870406]
7. Hudson BD, Tikhonova IG, Pandey SK, Ulven T, Milligan G. (2012) Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3. J Biol Chem, 287 (49): 41195-209. [PMID:23066016]
8. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J et al.. (2005) Antisense transcription in the mammalian transcriptome. Science, 309 (5740): 1564-6. [PMID:16141073]
9. Kebede MA, Alquier T, Latour MG, Poitout V. (2009) Lipid receptors and islet function: therapeutic implications?. Diabetes Obes Metab, 11 Suppl 4: 10-20. [PMID:19817784]
10. Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G. (2011) Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci USA, 108 (19): 8030-5. [PMID:21518883]
11. Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J et al.. (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem, 278 (28): 25481-9. [PMID:12711604]
12. Rasoamanana R, Darcel N, Fromentin G, Tomé D. (2012) Nutrient sensing and signalling by the gut. Proc Nutr Soc, 71 (4): 446-55. [PMID:22453062]
13. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M et al.. (2008) Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA, 105 (43): 16767-72. [PMID:18931303]
14. Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O'Dowd BF. (1997) A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem Biophys Res Commun, 239 (2): 543-7. [PMID:9344866]
15. Schmidt J, Smith NJ, Christiansen E, Tikhonova IG, Grundmann M, Hudson BD, Ward RJ, Drewke C, Milligan G, Kostenis E et al.. (2011) Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3. J Biol Chem, 286 (12): 10628-40. [PMID:21220428]
16. Seljeset S, Siehler S. (2012) Receptor-specific regulation of ERK1/2 activation by members of the "free fatty acid receptor" family. J Recept Signal Transduct Res, 32 (4): 196-201. [PMID:22712802]
17. Senga T, Iwamoto S, Yoshida T, Yokota T, Adachi K, Azuma E, Hamaguchi M, Iwamoto T. (2003) LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Blood, 101 (3): 1185-7. [PMID:12393494]
18. Sykaras AG, Demenis C, Case RM, McLaughlin JT, Smith CP. (2012) Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key endocannabinoid and fatty acid receptors. PLoS ONE, 7 (8): e42373. [PMID:22876318]
19. Tang C, Offermanns S. (2017) FFA2 and FFA3 in Metabolic Regulation. Handb Exp Pharmacol, 236: 205-220. [PMID:27757760]
20. Tazoe H, Otomo Y, Karaki S, Kato I, Fukami Y, Terasaki M, Kuwahara A. (2009) Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res, 30 (3): 149-56. [PMID:19574715]
21. Ulven T. (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocrinol (Lausanne), 3: 111. [PMID:23060857]
22. Wang A, Akers RM, Jiang H. (2012) Short communication: Presence of G protein-coupled receptor 43 in rumen epithelium but not in the islets of Langerhans in cattle. J Dairy Sci, 95 (3): 1371-5. [PMID:22365220]
23. Xiong Y, Miyamoto N, Shibata K, Valasek MA, Motoike T, Kedzierski RM, Yanagisawa M. (2004) Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci USA, 101 (4): 1045-50. [PMID:14722361]
24. Zaibi MS, Stocker CJ, O'Dowd J, Davies A, Bellahcene M, Cawthorne MA, Brown AJ, Smith DM, Arch JR. (2010) Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett, 584 (11): 2381-6. [PMID:20399779]
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