Epithelial sodium channel (IPR001873)

Short name: ENaC

Overlapping homologous superfamilies


Family relationships


The apical membrane of many tight epithelia contains sodium channels that are primarily characterised by their high affinity to the diuretic blocker amiloride [PMID: 8181670, PMID: 8905643, PMID: 8905643, PMID: 7499195]. These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis [PMID: 8181670]. In vertebrates, the channels control reabsorption of sodium in kidney, colon, lung and sweat glands; they also play a role in taste perception.

Members of the epithelial Na+ channel (ENaC) family fall into four subfamilies, termed alpha, beta, gamma and delta [PMID: 8905643]. The proteins exhibit the same apparent topology, each with two transmembrane (TM) spanning segments, separated by a large extracellular loop. In most ENaC proteins studied to date, the extracellular domains are highly conserved and contain numerous cysteine residues, with flanking C-terminal amphipathic TM regions, postulated to contribute to the formation of the hydrophilic pores of the oligomeric channel protein complexes. It is thought that the well-conserved extracellular domains serve as receptors to control the activities of the channels.

Vertebrate ENaC proteins are similar to degenerins of Caenorhabditis elegans [PMID: 7929098]: deg-1, del-1, mec-4, mec-10 and unc-8. These proteins can be mutated to cause neuronal degradation, and are also thought to form sodium channels.

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 [PMID: 7929098].

GO terms

Biological Process

GO:0006814 sodium ion transport

Molecular Function

GO:0005272 sodium channel activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.