GPR35 Membrane Protein Introduction

Introduction of GPR35

GPR35, also known as kynurenic acid receptor or KYNA receptor, is a protein encoded by the GPR35 gene. It was first identified in 1998 from rat intestine as a class A (rhodopsin-like) G protein-coupled receptor that contains 309 amino acids. As a kynurenic acid receptor, GPR35 can be activated by kynurenic acid at high micromolar concentrations.

Basic Information of GPR35
Protein Name Putative G-protein coupled receptor GPR35
Gene Name GPR35
Aliases Kynurenic acid receptor, KYNA receptor
Organism Homo sapiens (Human)
UniProt ID Q9HC97
Transmembrane Times 7
Length (aa) 340

Function of GPR35 Membrane Protein

GPR35 is a poorly characterized orphan G protein-coupled receptor (GPCR), which was first described as an intronless G protein-coupled receptor gene encoding 309 amino acids. It is reported to be expressed in diverse human tissues, which including but not limited to lungs, stomach, small intestine, colon, spleen, and immune cells (including mast cells, basophils, eosinophils, and invariant natural killer-like T cells). In recent years, studies have suggested that GPR35 has potential therapeutic value based on its association with several diseases, including cancer, inflammatory bowel disease, diabetes, hypertension, and heart failure. Furthermore, GPR35 gene expression has been detected in human primary vascular smooth muscle cells and endothelial cells from saphenous vein, and GPR35 agonists induced actin fiber reorganization and migration in vascular smooth muscle cells. And, heightened expression of GPR35 is also found in immune and gastrointestinal tissues, including the crypts of Lieberkühn.

Diagram illustrating the proposed mechanism by which GPR35 agonists suppress action potential firing in hippocampal interneurons. Fig.1 Diagram illustrating the proposed mechanism by which GPR35 agonists suppress action potential firing in hippocampal interneurons. (Alkondon, 2015)

Application of GPR35 Membrane Protein in Literature

  1. Divorty N., The Orphan Receptor GPR35 Contributes to Angiotensin II-Induced Hypertension and Cardiac Dysfunction in Mice. American Journal of Hypertension. 2018. PubMed ID: 29860395

    This article is conducted to assess the potential for GPR35 as a therapeutic target in cardiovascular disease. It demonstrates that GPR35 plays an important pathological role in the development of Ang II-induced hypertension and impaired cardiac function, which suggests that GPR35 can be used as a potential novel drug target for therapeutic intervention in hypertension.

  2. Agudelo L.Z., Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. Cell Metabolism. 2018, 27(2):378-92. PubMed ID: 29414686

    This article shows that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. It indicates that kynurenine metabolism may be used as a pathway with therapeutic potential to control energy homeostasis.

  3. Park S.J., GPR35 mediates lodoxamide-induced migration inhibitory response but not CXCL17-induced migration stimulatory response in THP-1 cells; is GPR35 a receptor for CXCL17? British Journal of Pharmacology. 2018, 175(1):154-61. PubMed ID: 29068046

    This research is conducted to investigate the correlation between CXCL17 and GPR35. It suggests that GPR35 functions as a migration inhibitory receptor, but CXCL17-stimulated migration of THP-1 cells is not dependent on GPR35.

  4. Ruiz-Pinto S., Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer. Pharmacogenetics and genomics. 2017, 27(12):445-53. PubMed ID: 28961156

    This article aims to identify new genes and low-frequency variants influencing the susceptibility to anthracycline-induced cardiotoxicity (AIC) for pediatric cancer patients. It shows that GPR35 is a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.

  5. Guo Y.J., The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer. Biochemical and biophysical research communications. 2017, 493(3):1159-67. PubMed ID: 28943434

    This article is conducted to investigate the role of the CXCL17-CXCR8 (GPR35) axis in breast cancer. It indicates that CXCL17 is a potential oncogene and promising therapeutic target, is an independent biomarker of poor prognosis in patients with breast cancer and can promote proliferation and migration of breast cancer cells.

GPR35 Preparation Options

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  1. Alkondon, et al. (2015). Functional G-protein-coupled receptor 35 is expressed by neurons in the CA1 field of the hippocampus. Biochemical Pharmacology, 93(4), 506-518.

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