GPR84 Membrane Protein Introduction

Introduction of GPR84

Probable G-protein coupled receptor 84 (GPR84) is a protein that in humans is encoded by the GPR84 gene. The gene locates to chromosome 12q13.13, and its coding sequence is not interrupted by introns. It turned out that GPR84 belongs to the Th1 specific subset genes. Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity. Among the related pathways of GPR84 are innate immune system and signaling by GPCR. Activation by medium-chain free fatty acid is coupled to a pertussis toxin sensitive G (i/o) protein pathway. May have important roles in processes from fatty acid metabolism to regulation of the immune system.

Basic Information of GPR84
Protein Name	G-protein coupled receptor 84
Gene Name	GPR84
Aliases	Inflammation-related G-protein coupled receptor EX33, EX33
Organism	Homo sapiens (Human)
UniProt ID	Q9NQS5
Transmembrane Times	7
Length (aa)	396
Sequence	MWNSSDANFSCYHESVLGYRYVAVSWGVVVAVTGTVGNVLTLLALAIQPKLRTRFNLLIANLTLADLLYCTLLQPFSVDTYLHLHWRTGATFCRVFGLLLFASNSVSILTLCLIALGRYLLIAHPKLFPQVFSAKGIVLALVSTWVVGVASFAPLWPIYILVPVVCTCSFDRIRGRPYTTILMGIYFVLGLSSVGIFYCLIHRQVKRAAQALDQYKLRQASIHSNHVARTDEAMPGRFQELDSRLASGGPSEGISSEPVSAATTQTLEGDSSEVGDQINSKRAKQMAEKSPPEASAKAQPIKGARRAPDSSSEFGKVTRMCFAVFLCFALSYIPFLLLNILDARVQAPRVVHMLAANLTWLNGCINPVLYAAMNRQFRQAYGSILKRGPRSFHRLH

Function of GPR84 Membrane Protein

The importance of GPCRs in the regulation of β-catenin signaling and tumorigenesis has been increasingly recognized. A recent report has identified GPR84 as a leukemia stem cell-specific gene. GPR84 may also play a proinflammatory role and can be used as a novel target to treat chronic low-grade inflammation associated-disease. Microglia surrounds the amyloid plaques that form in the brains of patients with Alzheimer's disease (AD) and these cells can express GPR84 under inflammatory conditions. GPR84 acts as a sensor for a yet unknown ligand that promotes microglia recruitment, thus preventing further cognitive decline by playing a role in amyloid pathology.

Fig.1 The Gi protein-coupled receptor GPR84, which is activated by (hydroxy) fatty acids, is highly expressed on immune cells. (Pillaiyar, 2017)

Application of GPR84 Membrane Protein in Literature

Dietrich P.A., et al. GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis. Blood. 2014, 124(22): 3284-94. PubMed ID: 25293777

The results reveal a previously unrecognized role of GPR84 in maintaining fully developed acute myeloid leukemia (AML) by sustaining aberrant β-catenin signaling in LSCs. It suggests that targeting the oncogenic GPR84/β-catenin signaling axis may represent a novel therapeutic strategy for AML.
Audoy-Rémus J., et al. GPR84 deficiency reduces microgliosis but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease. Brain Behav Immun. 2015, 46: 112-20. PubMed ID: 25637481

The article reports that GPR84 acts as a sensor for a yet unknown ligand that promotes microglia recruitment, thus preventing further cognitive decline by playing a role in amyloid pathology.
Suzuki M., et al. Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor. PLoS One. 2013, 288(15): 10684-91. PubMed ID: 23449982

The authors in this group found that GPR84 is a proinflammatory receptor and may be a novel target to treat chronic low-grade inflammation associated-disease.
Nikaido Y., et al. Mutation analysis and molecular modeling for the investigation of ligand-binding modes of GPR84. J Biochem. 2015, 157(5): 311-20. PubMed ID: 25425658

This article focuses on the mutation analysis and molecular modeling for the investigation of ligand-binding modes of GPR84. The results suggest that diindolylmethane is a positive allosteric modulator for GPR84.
Huang Q., et al. A medium-chain fatty acid receptor Gpr84 in zebrafish: expression pattern and roles in immune regulation. Dev Comp Immunol. 2014, 45(2): 252-8. PubMed ID: 24704214

This article evaluates the roles of Gpr84 in immune regulation. It shows that Gpr84 may play a role in directly linking fatty acid metabolism to immunological regulation.

GPR84 Preparation Options

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Reference

Pillaiyar T, et al. (2017). Diindolylmethane Derivatives: Potent Agonists of the Immunostimulatory Orphan G Protein-Coupled Receptor GPR84. J Med Chem. 60(9): 3636-3655.

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