Ask about this productRelated genes to: GPR174 Blocking Peptide
- Gene:
- GPR174 NIH gene
- Name:
- G protein-coupled receptor 174
- Previous symbol:
- -
- Synonyms:
- FKSG79
- Chromosome:
- Xq21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-09-02
- Date modifiied:
- 2016-10-05
Related products to: GPR174 Blocking Peptide
Related articles to: GPR174 Blocking Peptide
- The X-linked G-protein coupled receptor GPR174 is highly expressed in T and B lymphocytes and has immunoregulatory roles in mice, but its function in humans is unknown. We describe a cohort of six individuals who have function-disrupting variants in and a clinical phenotype of lymphadenopathy and autoimmunity. Histological analysis of two patient lymph nodes revealed necrotizing lymphadenitis and lymphoproliferation resembling Kikuchi-Fujimoto disease. In-depth analysis of three patients and related carriers revealed overaccumulation of CD8 terminally differentiated effector memory cells re-expressing CD45RA (T). Patient cells and GPR174-deficient CD8 T cells generated from controls showed less repression of proliferation by the GPR174 ligand lysophosphatidylserine (lysoPS) and an effector-biased gene expression program. GPR174-deficient CD4 T cells were resistant to lysoPS-mediated suppression of IL2 production. In mice, chronic viral infection led to over-accumulation of GPR174-deficient effector CD8 T cells. We describe an inborn error of immunity associated with dysregulated lymphocyte responses that we propose predisposes to exaggerated lymphoproliferation and autoimmunity following viral infection. - Source: PubMed
Publication date: 2026/07/17
Huang Yun-HanArana KathyaRachimi SuzannaTam HansonSpegarova Jarmila StremenovaEngelhardt Karin RGriffin HelenMee MollyMiano MaurizioRaggi FedericaGrossi AliceRusmini MartaCeccherini IsabellaDell'Orso GianlucaFerro JacopoGiarratana Maria CarlaPillai VinodhBanka SiddharthGarcez TomazBriggs Tracy AMellouli Fethivon Hardenberg SandraBeier RitaAuber BerndBaumann UlrichTawamie HasanBehrens EdwardOldridge Derek ACabrera Emylette CruzXu YingOuyang ShinyiHambleton SophieRomberg NeilCyster Jason G - Although changes in the lung microbiome have been observed in many respiratory diseases, the lung microbiome of patients with tuberculosis (TB) remains largely undefined. The aim of this study was to determine and compare the composition of upper and lower respiratory microbial communities, changes in host gene expression, and functional pathway activation in patients with TB and community-acquired pneumonia using a Metatranscriptomic approach. - Source: PubMed
Publication date: 2026/06/06
Li LiangyuXu MengLiu MenglingMao JieyuXiong PeiLi RuiyunChen JianjunWu Xiaojun - Sepsis is a systemic infection characterized by the dissemination of microbial pathogens through the bloodstream, and subsequently triggers inflammation, organ failure and concurrent immune suppression. The dysregulation of the innate and adaptive immune systems results in life-threatening organ failure or recurrent and often fatal infections. There are no effective and specific therapeutics due to the poorly understood underlying mechanisms. G-protein coupled receptors (GPCRs) are membrane-bound receptors that have emerged as important upstream regulators of immune system homeostasis and excessive inflammation, organ failure, and immune suppression in sepsis. Among GPCRs, orphan GPCRs are deficient of validated ligands and their function and therapeutics are underexplored. We critically discuss the functions of orphan GPCRs, especially GPR37, GPR43, GPR81 and GPR174 in sepsis. Activation of GPR37 and GPR43 is essential for enhanced phagocytic activity and diminished organ injury, thereby reducing mortality. Conversely, activation of GPR81 exacerbates sepsis through METTL3- and p300-mediated lung injury and increased endothelium permeability, while GPR174 promotes inflammation and increases mortality in septic rodents. In-depth analyses are conducted on the structure-based design, advantages and limitations of small-molecule orphan GPCR modulators, which indicate that GPR37 agonist artesunate and GPR43 agonist 4-CMTB are the most promising drug candidates for future optimization. We propose to design biased modulators that selectively activate orphan GPCR-coupled β-arrestin2, Gi, and Gq pathways, respectively, to enhance phagocytic activity and minimize inflammation. Taken together, specific orphan GPCR-coupled downstream signaling pathways present promising therapeutic targets for the treatment of sepsis. - Source: PubMed
Publication date: 2026/05/28
Wang YibingLin Yining - G protein-coupled receptor 174 (GPR174), a key modulator of autoimmune responses, maintains immune homeostasis through distinct G protein signaling pathways, particularly Gs and Gi. Although the structural mechanism of lysophosphatidylserine (LysoPS)-activated GPR174 in the Gs pathway has been characterized, how hydration-mediated interactions influence GPR174 activation and signaling selectivity remains unclear. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of LysoPS-activated human GPR174 bound to Gs (2.0 Å) and Gi (3.4 Å), revealing a continuous hydration-mediated signal transduction network that bridges the sodium-binding pocket, the NPxxY and DRY motifs, and the G protein-binding interface. This network stabilizes the active-state conformation of GPR174 and dynamically reshapes the intracellular cavity, thereby enabling differential engagement of Gs and Gi. Molecular dynamics simulations and functional assays demonstrated that the hydration network is essential for receptor activation and selectively modulates G protein coupling. To evaluate its conservation, we performed sequence alignments and structural analyses across class A GPCRs, defining three hydration cavities: the conserved water cavity (CWC), the junctional water cavity (JWC), and the extended water cavity (EWC), whose hydration is determined by residue properties at position 5.58. Together, our study reveals a hydration-driven molecular mechanism that underlies the activation of GPR174 and its dual G protein selectivity. These findings advance the understanding of hydration-mediated signaling in GPR174 and provide a framework for investigating water-mediated regulation across class A GPCRs. - Source: PubMed
Publication date: 2026/05/07
Dong Ying-JunXi KunZhang Ya-ZhiXue Jian-HengShen Dan-DanZang Shao-KunZhao RuozhuQi HaiMao ChunyouWang Wei-WeiZhang Yan - GPR174 is an immune-restricted G-protein-coupled receptor (GPCR) constitutively activated by lysophosphatidylserine (LysoPS). Elevated LysoPS in the tumor microenvironment may sustain GPR174 activity, promoting immunosuppression and resistance to cancer immunotherapies. Here, we modeled GPR174 bound to an antagonist mPS (modified LysoPS) and performed extensive molecular dynamics (MD) simulations in a heterogeneous lipid bilayer, with parallel simulations of the LysoPS-bound receptor for comparison. mPS binding inactivated GPR174 and resulted in reduced conformational dynamics, persistent hydrogen bonding interactions, and selective interactions with transmembrane helix 1. In contrast, LysoPS exhibited greater conformational flexibility, multiple binding poses, and transient acyl chain displacement into the membrane. Network analysis revealed that LysoPS engaged conserved activation motifs (PIF, DRY, N/DPxxY) to couple the ligand binding site to the G-protein interface, whereas these pathways were disrupted by mPS. Protein-lipid analyses further suggested that membrane lipids, including phosphatidylinositol (PIP2), modulate ligand dynamics and receptor conformational states. Collectively, these findings highlight distinct ligand-specific mechanisms of GPR174 modulation and provide a framework for rational design of selective antagonists with immunotherapeutic potential. - Source: PubMed
Publication date: 2025/09/19
Bhardwaj Vijay KumarGorfe Alemayehu