BESTs transport cytosolic Cl- to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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Bestrophins 1-4 (BEST1-4, aka vitelliform macular dystrophy proteins) mediate cytosolic Cl- efflux across plasma membranes. This transport is sensitive to intracellular Ca2+ concentrations (Sun et al. 2002, Tsunenari et al. 2003). Mutations in bestrophins that impair their function are implicated in macular degeneration in the eye. Defects in BEST1 cause vitelliform macular dystrophy (BVMD, Best's disease, MIM:153700), an autosomal dominant form of macular degeneration that usually begins in childhood and is characterized lesions due to abnormal accumulation of lipofuscin within and beneath retinal pigment epithelium (RPE) cells (Marquardt et al. 1998, Petrukhin et al. 1998). All CLCAs contain a consensus cleavage motif which is recognised by an internal zincin metalloprotease domain within the N terminus. Self-proteolysis within the secretory pathway yields N- and C-terminal fragments, a step critical for CLCA activation of calcium-activated chloride channels (CaCCs) mediated through the N-terminal fragment (Yurtsever et al. 2012).
Literature References
PubMed ID Title Journal Year
11904445 The vitelliform macular dystrophy protein defines a new family of chloride channels

Yau, KW, Sun, H, Nathans, J, Tsunenari, T

Proc. Natl. Acad. Sci. U.S.A. 2002
9662395 Identification of the gene responsible for Best macular dystrophy

Li, W, Bergen, AA, Petrukhin, K, Austin, CP, Caskey, CT, Forsman, K, Koisti, MJ, Wadelius, C, Marknell, T, Holmgren, G, Figueroa, D, Andreasson, S, Sandgren, O, Bakall, B, Vujic, M, Metzker, ML, Xie, G, McGarty-Dugan, V

Nat. Genet. 1998
12907679 Structure-function analysis of the bestrophin family of anion channels

Yau, KW, Williams, J, Sun, H, Smallwood, P, Nathans, J, Tsunenari, T, Cahill, H

J. Biol. Chem. 2003
9700209 Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)

Stöhr, H, Weber, BH, Rivera, A, Passmore, LA, Krämer, F, Marquardt, A

Hum. Mol. Genet. 1998
Catalyst Activity

chloride channel activity of BESTs [plasma membrane]

This event is regulated
Orthologous Events
Cross References
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