G protein-coupled receptor 84

Function

G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists. In immune cells, functions as a pro-inflammatory receptor via 6-OAU and promotes the expression of pro-inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as stimulating chemotactic responses through activation of signaling mediators AKT, ERK and NF-kappa-B (By similarity). In addition, triggers increased bacterial adhesion and phagocytosis in macrophages and regulates pro-inflammatory function via enhancing NLRP3 inflammasome activation (By similarity). Also plays an important role in inflammation by modulating neutrophil functions (By similarity). Mechanistically, promotes neutrophil chemotaxis, reactive oxygen species (ROS) production and degranulation via LYN-AKT/ERK pathway (By similarity). To regulate ROS, communicates with the two formyl peptide receptors FPR2 and FPR1 to control the NADPH oxidase activity in neutrophils.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 4

• 8G05 EM 3.00A
• 8J18 EM 2.89A
• 8J19 EM 3.23A
• 8J1A EM 3.24A

A predicted model is available from AlphaFold.

Gene Ontology · 6

• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0035579 specific granule membrane
• GO:0070821 tertiary granule membrane
• GO:0001604 urotensin II receptor activity
• GO:0007218 neuropeptide signaling pathway

Drugs targeting this protein · 2

• GLPG-1205 negative allosteric modulator
• SETOGEPRAM antagonist

Related proteins · sequence + function similarity

• G protein-coupled receptor 84 0.99
• G protein-coupled receptor 84 0.98
• Melatonin receptor type 1A 0.91
• Melatonin receptor type 1B-B 0.90
• Melatonin receptor type 1A-A 0.90
• Melatonin receptor type 1C 0.90
• Melatonin receptor type 1A 0.90
• Melatonin receptor type 1B 0.90
• Melatonin receptor type 1C 0.90
• Melatonin receptor type 1B 0.89
• Melatonin receptor type 1A 0.89
• Melatonin receptor type 1A 0.89

Co-cited proteins · studied together in the literature

• G protein-coupled receptor 84 2 shared papers
• Arrestin-C 1 shared papers
• Mas-related G protein-coupled receptor member H 1 shared papers
• P2Y purinoceptor 13 2 shared papers
• Succinate receptor 1 1 shared papers
• G protein-coupled receptor 87 1 shared papers
• Beta-arrestin-2 1 shared papers
• Succinate receptor 1 1 shared papers
• G protein-coupled receptor 87 1 shared papers
• Putative vomeronasal receptor-like protein 4 1 shared papers
• Probable G protein-coupled receptor 160 1 shared papers
• Probable G protein-coupled receptor 152 1 shared papers

Literature · 8 cited papers

• Selective phosphorylation of threonine residues defines GPR84-arrestin interactions of biased ligands. J. Biol. Chem. · 2022
• The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity. J. Innate Immun. · 2021
• Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. · 2012
• Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett. · 2002
• Cloning and expression analysis of a novel G-protein-coupled receptor selectively expressed on granulocytes. J. Leukoc. Biol. · 2001
• An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J. Mol. Biol. · 2001