TBXA2R Membrane Protein Introduction

Introduction of TBXA2R

TBXA2R belongs to the G-protein coupled receptor 1 family. Encoded by TBXA2R gene, TBXA2R is composed of 407 amino acids with 7 putative transmembrane domains. TBXA2R has a broad expression in fat, spleen and 20 other tissues. The protein can interact with thromboxane A2 to induce platelet aggregation and regulate hemostasis. Mutations in this gene may result in a bleeding disorder. TBXA2R has multiple transcript variants encoding different isoforms.

Function of TBXA2R Membrane Protein

As a powerful stimulator of platelet aggregation, TBXA2R plays an essential role in hemostasis by interacting with thromboxane A2 (TXA2), which is an arachidonate metabolite. At present, TXA2 has been well recognized as a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles. The activity of TBXA2R is mediated by a G-protein, which can activate a phosphatidylinositol-calcium second messenger system. It is documented that when binding to glomerular TP receptors in the kidney, TXA2 will cause intense vasoconstriction. Isoform 1 of TBXA2R can activate adenylyl cyclase, however, the isoform 2 may lead to inhibition of adenylyl cyclase. This receptor has guanyl-nucleotide exchange factor activity and thromboxane A2 receptor activity. There is no experiment structure of TBXA2R available so far. TBXA2R has been implicated to be associated with various diseases such as myocardial infarction, stroke, and bronchial asthma.

Fig.1 A theoretical model of TBXA2R.

Application of TBXA2R Membrane Protein in Literature

1. Orr K., et al. Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs). Oncotarget. 2016, 7(34):55458-55472. PubMed ID: 27487152
   
   

   This article demonstrates that TBXA2R strengthens TNBC cell migration, invasion and activated Rho signaling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protects TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behavior of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.

2. Kavalar M.S., et al. Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma. Int J Immunogenet. 2012, 39(1):20-5. PubMed ID: 22017802
   
   

   This article confirms ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms are not associated with asthma risk, but they are associated with asthma-related symptoms.

3. Palikhe N.S., et al. Association of thromboxane A2 receptor (TBXA2R) gene polymorphism in patients with aspirin-intolerant acute urticaria. Clin Exp Allergy. 2011, 41(2):179-85. PubMed ID: 21070398
   
   

   This article suggests that the TBXA2R-4684T allele may have a connection with lower TBXA2R expression, which may cause the development of the AIAU phenotype.

4. Takeuchi K., et al. Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood-onset asthma. Clin Exp Allergy. 2013, 43(4):413-24. PubMed ID: 23517037
   
   

   This article demonstrates that genetic variants identified in the TBXA2R gene may influence transcriptional activity and may be associated with asthma-related phenotypes. Thromboxane pathways may, therefore, have a significant influence on airway inflammation and remodeling in asthma patients.

5. Pan Y., et al. Association between thromboxane A2 receptor polymorphisms and asthma risk: A meta-analysis. J Asthma. 2016, 53(6):576-82. PubMed ID: 27058349
   
   

   This article suggests that TBXA2R +924C/T polymorphism is associated with asthma risk, and +795C/T polymorphism may be a risk factor for AIA. Larger-scale and well-designed studies are required to validate the association identified in the current meta-analysis.

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