Bestrophin-1 | BEST1

Family:
Calcium-dependent chloride channels (Ca-CIC or CaCC family)

Members:
CaCCs that are known to occur in humans are encoded by the following genes:
Accessories: CLCA1 - CLCA4
Anoctamins: ANO-1 and ANO-2
Bestrophins: BEST1 - BEST4

Topology:
CaCC channels are a heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells, including proteins from several structurally different families: chloride channel accessory (CLCA), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels. Members of the Ca-CIC family exhibit 7 to 10 transmembrane segments.

BEST1 Background Information


Overview:

The bestrophins are an ancient family of structurally conserved proteins that have been identified in nearly every organism studied from bacteria to humans. In humans, they form chloride channels that are activated by physiological concentrations of Ca2+. Each of the four BEST channels has a unique tissue distribution throughout the body. Specifically, the BEST1 gene on chromosome 11q13 encodes the Bestrophin-1 protein in humans whose expression is highest in the retina. Mutations in the BEST1 gene have been identified as the primary cause for at least five different degenerative retinal diseases.


Data Sheet:

Gene:
BEST1

Human Protein:
UniProt O76090

Tissue:
Retina: Predominantly expressed in the basolateral membrane of the retinal pigment epithelium

Function/ Application:
Best1 primarily functions as an intracellular calcium-activated chloride channel on the cellular membrane that is not voltage-dependent. Best1 has been shown to act as a volume-regulating anion channel.

Pathology:
Best vitelliform macular dystrophy (BVMD), Adult-onset vitelliform macular dystrophy (AVMD), Autosomal recessive bestrophinopathy (ARB), Autosomal dominant vitreoretinochoroidopathy, Retinitis pigmentosa (RP), Stargardt disease

Interaction:
Homooligomer (tetramer or pentamer). May interact with PPP2CB (Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform) and PPP2R1B (Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform).

Modulator:
Calcium, Carbonic acid

Assays:
Lipid bilayer recordings on the Port-a-Patch or Orbit

Reviews and Links

Publications

2018 - An allosteric mechanism of inactivation in the calcium-dependent chloride channel BEST1

icon pap   Port-a-Patch publication in Journal of General Physiology (2018)

Authors:
Vaisey G., Long S.B.

2016 - Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel

icon pap  Port-a-Patch publication in Proceedings of the National Academy of Sciences of the United States of America (2016)

Authors: 
Vaisey G., Miller A.N., Long S.B.

 

 

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