ATP2B1 Membrane Protein Introduction

Introduction of ATP2B1

Plasma membrane calcium-transporting ATPase 1 (ATP2B1) is a plasma membrane Ca²⁺ ATPase and is encoded by the ATP2B1 gene. It belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. The structure of ATP2B1 consists of 10 transmembrane domains, two large intracellular loops and one N- and C-terminal cytoplasmic tails, amongst the C-terminal domain is referred to as a regulatory domain. There are six isoforms of ATP2B1 have already been found and different isoforms may have different tissue specificities and different functions.

Function of ATP2B1 Membrane Protein

As an important member of P-type primary ion transport ATPases family, ATP2B1 plays an essential role in the intracellular Ca²⁺ extrusion of eukaryotic cells and is indispensable for intracellular calcium homeostasis. ATP2B1 is a magnesium-dependent enzyme catalyzing the hydrolysis of ATP coupled with the transport of calcium out of the cell. By extruding Ca²⁺ from cells, ATP2B1 contributes to maintaining the resting level of intracellular Ca²⁺ and controlling the Ca²⁺ transients induced by agonists. It has been reported that ATP2B1 mediated Ca²⁺ clearance from hippocampal neurons can be accelerated in the presence of HOMER proteins. Interestingly, ATP2B1 are functionally adapted to the physiological needs of particular cells and tissues via alternative splicing of transcripts.

Fig.1 The predicted structure of ATP2B1 from SWISS-MODEL Repository. ( Bienert, 2017)

Application of ATP2B1 Membrane Protein in Literature

1. Hirawa N., et al. ATP2B1 and blood pressure: from associations to pathophysiology. Curr Opin Nephrol Hypertens. 2013, 22(2): 177-84. PubMed ID: 23324996
   
   

   This article demonstrates that ATP2B1 has a strong influence on blood pressure, being a hypertension-susceptibility gene in large-scale GWAS studies. Vascular smooth muscle cell ATP2B1 knockout mice exhibit high blood pressure in radio telemetry-based experiments.

2. Fujiwara A., et al. Impaired nitric oxide production and increased blood pressure in systemic heterozygous ATP2B1 null mice. J Hypertens. 2014, 32(7): 1415-23. PubMed ID: 24805951
   
   

   This article suggests that reduced expression of ATP2B1 gene is associated with repressed endothelial NOS activity and nitric oxide production, and the ATP2B1 gene plays a significant role in the regulation of blood pressure.

3. Shin Y.B., et al. Silencing of Atp2b1 increases blood pressure through vasoconstriction. J Hypertens. 2013, 31(8): 1575-83. PubMed ID: 23666421
   
   

   This article confirms that blood pressure is regulated by ATP2B1 through the dilation and contraction of the vessel, possibly by controlling calcium concentrations in the resting state, further demonstrates ATP2B1 expression in the vessel influences blood pressure.

4. Wang Y., et al. Common variants in the ATP2B1 gene are associated with hypertension and arterial stiffness in Chinese population. Mol Biol Rep. 2013, 40(2): 1867-73. PubMed ID: 23079715
   
   

   This article performs the current replication study to test the association of ATP2B1 gene and blood pressure and hypertension in two uncorrelated Chinese cohorts, including 1,987 controls and 2,831 uncorrelated hypertensive patients in total.

5. Xu J., et al. Gender-Specific Association of ATP2B1 Variants with Susceptibility to Essential Hypertension in the Han Chinese Population. Biomed Res Int. 2016, 2016: 1910565. PubMed ID: 26933664
   
   

   This article indicates that BMI can significantly affect the development of hypertension by stratified analysis and Crossover analysis, while ATP2B1 variants have a minor effect.

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Reference

1. Bienert S, et al. (2017). The SWISS-MODEL Repository - new features and functionality. Nucleic Acids Res. 45: D313-D319.

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