PROSITE documentation PDOC00926

Amiloride-sensitive sodium channels signature

Amiloride-sensitive sodium channels (ASC) [1,2,3] are sodium permeable non-voltage-sensitive ion channels inhibited by the diuretic amiloride. They mediate the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. In vertebrates, these channels control the reabsorption of sodium in kidney, colon, lung and sweat glands. They also play a role in taste perception. The ASC are composed of three homologous subunits, called α, β and γ. A fourth subunit (delta) can replace the α subunit [4]. The vertebrate ASC subunits are homologous to the degenerins [5] of Caenorhabditis elegans: deg-1, del-1, mec-4, mec-10 and unc-8. They are proteins that can be mutated to cause neuronal degradation. They are also thought to form sodium channels.

This family also includes:

• Mammalian amiloride-sensitive brain sodium channel BNAC1 (also known as degenerin channel MDEG). This is a cation channel permeable for sodium, potassium and lithium.
• Caenorhabditis elegans hypothetical proteins C41C4.5, T28F4.2 and ZK770.1.

Structurally, the proteins that belong to this family consist of about 510 to 920 amino acid residues. They are made of an intracellular N-terminus region followed by a transmembrane domain, a large extracellular loop, a second transmembrane segment and a C-terminal intracellular tail [6].

The signature we developed to pick up these proteins corresponds to the beginning of a conserved cysteine-rich region (there are nine conserved cysteines in a domain of about 65 residues) located at the C-terminal part of the extracellular loop.