BEST1 Membrane Protein Introduction

Introduction of BEST1

Bestrophin-1 (BEST1) is encoded by the BEST1 gene. The bestrophin protein family includes four evolutionarily related genes (BEST1, BEST2, BEST3, and BEST4) encoding integrated membrane proteins. The family was first discovered in humans by linking the BEST1 mutation to the best yolk-like macular dystrophy (BVMD). In humans, bestrophins function as calcium-activated anion channels, each channel having a unique tissue distribution throughout the body. Specifically, the BEST1 gene on chromosome 11q13 encodes a BEST1 protein in humans, which is most highly expressed in the retina. The mutation of the BEST1 gene has been identified as the leading cause of at least five different degenerative retinal diseases.

Basic Information of BEST1
Protein Name	Bestrophin-1
Gene Name	BEST1
Aliases	VMD2, TU15B, VMDP2, BMD, RP50
Organism	Homo sapiens (Human)
UniProt ID	O76090
Transmembrane Times	20
Length (aa)	585
Sequence	MTITYTSQVANARLGSFSRLLLCWRGSIYKLLYGEFLIFLLCYYIIRFIYRLALTEEQQLMFEKLTLYCDSYIQLIPISFVLGFYVTLVVTRWWNQYENLPWPDRLMSLVSGFVEGKDEQGRLLRRTLIRYANLGNVLILRSVSTAVYKRFPSAQHLVQAGFMTPAEHKQLEKLSLPHNMFWVPWVWFANLSMKAWLGGRIRDPILLQSLLNEMNTLRTQCGHLYAYDWISIPLVYTQVVTVAVYSFFLTCLVGRQFLNPAKAYPGHELDLVVPVFTFLQFFFYVGWLKVAEQLINPFGEDDDDFETNWIVDRNLQVSLLAVDEMHQDLPRMEPDMYWNKPEPQPPYTAASAQFRRASFMGSTFNISLNKEEMEFQPNQEDEEDAHAGIIGRFLGLQSHDHHPPRANSRTKLLWPKRESLLHEGLPKNHKAAKQNVRGQEDNKAWKLKAVDAFKSAPLYQRPGYYSAPQTPLSPTPMFFPLEPSAPSKLHSVTGIDTKDKSLKTVSSGAKKSFELLSESDGALMEHPEVSQVRRKTVEFNLTDMPEIPENHLKEPLEQSPTNIHTTLKDHMDPYWALENRDEAHS

Function of BEST1 Membrane Protein

BEST1 acts primarily as an intracellular calcium-activated chloride channel on the cell membrane that is independent of voltage. Recently, BEST1 has been shown to act as a volume-regulating anion channel. BVMD is one of the most common BEST1 related diseases. Mutation of the BEST1 gene results in loss of channel function and ultimately leads to retinal degeneration. Loss of function of the BEST1 chloride channel may explain some of the most common problems associated with BVMD: the inability to modulate intracellular ion concentration and regulate overall cell volume. In addition, some studies have shown that BEST1 is also associated with diseases such as yolk-like macular dystrophy (AVMD) and autosomal recessive hereditary pterygium (ARB) in adults.

Fig.1 Structure of BEST1 membrane protein.

Application of BEST1 Membrane Protein in Literature

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.
Qu Z., et al. Bestrophin Cl- channels are highly permeable to HCO3-. Am J Physiol Cell Physiol. 2008, 294(6): C1371-7. PubMed ID: 18400985

Authors in this group apply their experiment results raise the possibility that disease-causing mutations in hBEST1 produce disease by altering HCO3(-) homeostasis as well as Cl(-) transport in the retina.
Davidson A.E., et al. Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa. Am J Hum Genet. 2009, 85(5): 581-92. PubMed ID: 19853238

This article reveals that in a model system of a polarized epithelium, two of three mutations (p.L140V and p.D228N) caused mislocalization of BEST1 from the basolateral membrane to the cytoplasm. Mutations in BEST1 are increasingly recognized as an important cause of inherited retinal dystrophy.
Caldwell G.M., et al. Bestrophin gene mutations in patients with Best vitelliform macular dystrophy. Genomics. 1999, 58(1): 98-101. PubMed ID: 10331951

This article identified possible mutation hotspots within the BEST gene, suggesting that particular regions of the protein have greater functional significance than others.
Yanagi Y., et al. Identification of a novel VMD2 mutation in Japanese patients with Best disease. Ophthalmic Genet. 2002, 23(2): 129-33. PubMed ID: 1287431

This article indicates a novel disease-causing mutation in the VMD2 gene (T990C) was found in Japanese patients with Best disease.

BEST1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-BEST1 antibody development services.

As a forward-looking research institute as well as a leading customer service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

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