{"id":"b87ae3ac-c0e7-512d-8779-7c3e78dbc6fc","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-ffar3-chain-length","predicate":"binds","statement":"GPR41 is 52% similar and 43% identical to GPR43 and was activated by similar ligands but with differing specificity for carbon chain length, pentanoate being its most potent agonist; GPR41 was expressed primarily in adipose tissue while the highest levels of GPR43 were in immune cells, and a third family member GPR42 is most likely a recent gene duplication of GPR41 and may be a pseudogene.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4c0270eb-d5fb-58f9-874a-589a8e38fb58","mechanism_event_label":"A sister receptor prefers longer fatty acids, and the two sit in different tissues.","subject":{"id":"747bf692-56f7-59fd-98c2-e84a6f02dcb7","slug":"ffar3","display_name":"Human free fatty acid receptor 3 / FFAR3","entity_type_key":"protein"},"object":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4c0270eb-d5fb-58f9-874a-589a8e38fb58","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-ffar3-chain-length-event","event_type":"biochemical_relationship","label":"A sister receptor prefers longer fatty acids, and the two sit in different tissues.","description":"GPR41 is 52% similar and 43% identical to GPR43 and was activated by similar ligands but with differing specificity for carbon chain length, pentanoate being its most potent agonist; GPR41 was expressed primarily in adipose tissue while the highest levels of GPR43 were in immune cells, and a third family member GPR42 is most likely a recent gene duplication of GPR41 and may be a pseudogene.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0a2fbe31-7973-535a-9662-8cbdb53246a9","slug":"pentanoate","display_name":"Pentanoate / valerate","entity_type_key":"small_molecule"},"role":"preferred_agonist","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fd3eea69-95f0-59b0-b56c-23ce0f98d311","slug":"gpr42","display_name":"GPR42, a probable recent duplication of GPR41 and possibly a pseudogene","entity_type_key":"gene"},"role":"probable_pseudogene","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"747bf692-56f7-59fd-98c2-e84a6f02dcb7","slug":"ffar3","display_name":"Human free fatty acid receptor 3 / FFAR3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/acetate-research/12496283.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f\", \"start_char\": 0, \"end_char\": 1291, \"text_sha256\": \"83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetic-acid","display_name":"Acetic acid","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human and mouse receptors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A sister receptor prefers longer fatty acids, and the two sit in different tissues.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[acetate-p12496283] The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. (2003). https://pubmed.ncbi.nlm.nih.gov/12496283/ DOI: 10.1074/jbc.m211609200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Transfected mammalian cells and Xenopus oocytes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"462b13c1-fca3-5661-8e45-0246a96011c7","evidence_kind":"source_excerpt","locator":"Lines 238-249","start_line":238,"end_line":249,"excerpt":"### acetate-ffar3-chain-length\nGPR41 is 52% similar and 43% identical to GPR43 and was activated by similar ligands but with differing specificity for carbon chain length, pentanoate being its most potent agonist; GPR41 was expressed primarily in adipose tissue while the highest levels of GPR43 were in immune cells, and a third family member GPR42 is most likely a recent gene duplication of GPR41 and may be a pseudogene.\nCondition category: normal\nnutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.\nplain_language: A sister receptor prefers longer fatty acids, and the two sit in different tissues.\norganism: Human and mouse receptors\ntissue_or_cell_type: Transfected mammalian cells and Xenopus oocytes\nexperimental_model: Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression\nlimitations: The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear.\nexposure: Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/12496283.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f\", \"start_char\": 0, \"end_char\": 1291, \"text_sha256\": \"83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f\"}\n[acetate-p12496283] The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. 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