GPR174 Membrane Protein Introduction

Introduction of GPR174

GPR174 belongs to the G-protein-coupled receptor (GPCR) family of which one action is to regulate diverse aspects of T-cell activity and effector function. It is well known that one-third of marketed medicines exert their pharmacological effects by acting on human GPCRs. GPR174 is encoded by the GPR174 gene. In humans, the GPR174 gene is located on chromosome X, region q21, in a cluster consisting of p2y10 and lpa4 genes. At the same time, phylogenetic analysis shows that GPR174 belongs to the P2Y family and has 50% sequence homology with P2Y10 receptor.

Basic Information of GPR174
Protein Name Probable G-protein coupled receptor 174
Gene Name GPR174
Aliases FKSG79, GPCR17
Organism Homo sapiens (Human)
UniProt ID Q9BXC1
Transmembrane Times 7
Length (aa) 333

Function of GPR174 Membrane Protein

GPR174 is widely expressed by immune cells and appear to be important regulators of immunity, i.e. anti-inflammatory. It has been showed that GPR174 mediates the suppression of T-cell proliferation in vitro induced by the polar lipid lysophosphatidylserine (LysoPS). GPR174 as an abundantly expressed Gas-dependent receptor that can negatively regulate naive T-cell activation. Besides, it is a receptor for LysoPS. In vitro experiments established that Gas (Adenylate Cyclase stimulation) G proteins are needed for LysoPS/GPR174-mediated suppression of T-cell proliferation. In addition, GPR174 is activated by LysoPS and stimulated transforming growth factor-a ectodomain shedding, through activating Ga12/13 protein. At the same time, another study also confirmed that GPR174 appears to be one of the most widely expressed GPCRs that signal through the G-protein. It’s also worth mentioning that genetic association studies identified linkages of GPR174 to Grave’s disease and Addison’s disease.

Gas-coupled GPCRs and the basics of downstream events. Fig.1 Gas-coupled GPCRs and the basics of downstream events. (Robert, 2018)

Application of GPR174 Membrane Protein in Literature

  1. Robert R. and Mackay C.R., Gαs-coupled GPCRs GPR65 and GPR174. Downers for immune responses. Immunol Cell Biol. 2018, 96, 341-343. PubMed ID: 29542190

    This article reports that GPR174 is one of the most widely expressed GPCRs that signal through the G-protein, and Gas signaling through Gas leads to cAMP production, which is (usually) anti-inflammatory.

  2. Barnes M.J. and Cyster J.G. Lysophosphatidylserine suppression of T-cell activation via GPR174 requires Gαs proteins. Immunol Cell Biol. 2018, 96: 439-445. PubMed ID: 29457279

    This article reveals that GPR174 expression can constrain T-cell proliferation, LysoPS acts via GPR174 and Gαs to suppress IL-2 production by activated T cells and limit upregulation of the activation markers CD25 and CD69. In conclusion, GPR174 is an abundantly expressed Gαs-dependent receptor that can negatively regulate naive T-cell activation.

  3. Shinjo Y., et al. Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through LPS3/GPR174. Biochem Biophys Res Commun. 2017, 494(1-2). PubMed ID: 29017923

    Authors in this group find that LysoPS suppressed IL-2 production in CD4 T cells via LPS3/GPR174, suggesting that LysoPS negatively regulates T cell-mediated adaptive immunity.

  4. Huang Y.J, et al. Alteration of Gene Expression Profiling Including GPR174 and GNG2 is Associated with Vasovagal Syncope. Pediatric Cardiology. 2015, 36(3), 475. PubMed ID: 25367286

    This article mainly discusses that alteration of gene expression profiling including GPR174 and GNG2 is associated with vasovagal syncope. This study provides new insight into the molecular mechanism of VVS and would be helpful to further identify new molecular biomarkers for the disease.

  5. Napier C., et al. Role of the X-linked gene GPR174 in autoimmune Addison's disease. Journal of Clinical Endocrinology & Metabolism. 2015, 100(1),187-90. PubMed ID: 25295623

    This article evaluates the role of the X-linked gene GPR174 in autoimmune Addison's disease, GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues.

GPR174 Preparation Options

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  1. Robert R and Mackay C R, (2018). Gαs-coupled gpcrs gpr65 and gpr174. downers for immune responses. Immunology & Cell Biology. 96(4).

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