InterPro domain: IPR021134

Bestrophin is a 68kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram [ 1 ]. VMD2 encodes a 585-amino acid protein with an approximate mass of 68kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of calcium-activated chloride channels (CaCC) [ 2 ], indicating a direct role for bestrophin in generating the light peak [ 3 , 3 , 4 ]. Bestrophins are also permeable to other monovalent anions including bicarbonate, bromine, iodine, thiocyanate an nitrate [ 5 , 5 ]. Structural analysis revealed that N-terminal region of the proteins is highly conserved and sufficient for its CaCC activity. The C-terminal region has low sequence identity. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal domain altering the electrophysiological properties of the channel [ 5 , 5 ].

This entry also includes uncharacterised proteins belonging to protein family UPF0187.

1. Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family. Eur. J. Hum. Genet. 10, 281-4
2. Structure and insights into the function of a Ca(2+)-activated Cl(-) channel. Nature 516, 213-8
3. Structure-function analysis of the bestrophin family of anion channels. J Biol Chem 278, 41114-25
4. Bestrophin Cl- channels are highly permeable to HCO3-. Am J Physiol Cell Physiol 294, C1371-7
5. Bestrophin interacts physically and functionally with protein phosphatase 2A. J. Biol. Chem. 277, 30591-7