BEST2 Membrane Protein Introduction

Introduction of BEST2

Bestrophin 2 (BEST2) is a member of the Bestrophin/RFP-TM protein family. There are four paralogous bestrophin genes in mammals, named Best1 to Best4. BEST2 is a protein encoded by the BEST2 gene in humans. However, the localization of BEST2 is only known in mice. Using mice in which the BEST2 gene was disrupted by insertion of the Lac Z reporter gene, we found that the BEST2 gene expression was the strongest in non-pigmented epithelial cells (NPE), eye and colon epithelial cells. Antibodies specific for mouse BEST2 (mBest2) confirmed these findings and showed that mBest2 localizes to the basolateral plasma membrane of those cells. mBest2 is also expressed in olfactory epithelial cells and salivary acinar cells.

Function of BEST2 Membrane Protein

This BEST2 gene is a member of the bestrophin gene family of anion channels and is mainly expressed in the non-pigmented ciliary epithelium and colon. Bestrophins are transmembrane proteins that contain homologous regions rich in aromatic residues, including the invariant arg-phe-pro motif. It is a recently recognized family of proteins linked to Ca²⁺ sensitive Cl⁻ transport. Several studies have demonstrated that these proteins play an important role in Ca²⁺-sensitive Cl⁻ transport, although they may have other functions as well. Among which, BEST2-associated Cl⁻ currents are perhaps the best characterized. Extensive mutagenesis of the second transmembrane domain in BEST2 has identified amino acid residues that appear to confer ion selectivity, revealing that bestrophins can form channel pores.

Fig.1 Structure of bestrophin ion channels.

Application of BEST2 Membrane Protein in Literature

1. Stöhr H., et al. Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family. Eur J Hum Genet. 2002, 10(4): 281-4. PubMed ID: 12032738
   
   

   This article identified three novel VMD2-related human genes (BEST2, VMD2L2, and VMD2L3) demonstrating a high degree of conservation in their respective RFP-TM domains. Each of the VMD2-like proteins has a unique C-terminus that lack similarity to other proteins or motifs.

2. Zhang Y., et al. Bestrophin 2 is expressed in human non-pigmented ciliary epithelium but not retinal pigment epithelium. Mol Vis. 2010, 16: 200-6. PubMed ID: 20157619
   
   

   Authors in this group find expression of hBEST2 similar to mice only in NPE cells. These data suggest that BEST2 may play a functional role in the regulation of aqueous flow and drainage in humans.

3. Yu K., et al. Bestrophin-2 mediates bicarbonate transport by goblet cells in mouse colon. J Clin Invest. 2010, 120(5): 1722-35. PubMed ID: 20407206
   
   

   This article delineates an alternative model of cholinergic regulation of colonic anion secretion in which goblet cells play a critical role in HCO3- homeostasis. BEST2 is a HCO3- channel that works in concert with a Cl: HCO3- exchanger in the apical membrane to affect transcellular HCO3- transport.

4. Ito G., et al. Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells. PLoS One. 2013, 8(11): e79693. PubMed ID: 24223998
   
   

   This article confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

5. Tsunenari T., et al. Structure-function analysis of the bestrophin family of anion channels. J Biol Chem. 2003. PubMed ID: 12907679
   
   

   This article reports that mapping of transmembrane topography by insertion of N-linked glycosylation sites and tobacco etch virus protease cleavage sites provide evidence for cytosolic N and C termini and an unexpected transmembrane topography with at least three extracellular loops that include positions 60-63, 212-227, and 261-267. These experiments provide the first structural analysis of the bestrophin channel family.

BEST2 Preparation Options

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