Bestrophin-1 | BEST1

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

Recommended Reviews:

• Huang et al.: International Union of Basic and Clinical Pharmacology. LXXXV: Calcium-Activated Chloride Channels; Pharmacol Rev. 64(1): 1–15, 2012; doi: 10.1124/pr.111.005009

Transporter classification database:

• 1.A.46.1.1 Bestrophin-1 (Best1) anion channel

UniProt:

• Bestrophin-1 (BEST1, Homo sapiens)

IUPHAR/PBS:

• Calcium activated chloride channel