Consensus pattern: Y-x(2)-[EQTF]-x-C-x(2)-[GSTDNL]-C-x-[QT]-x(2)-[LIVMT]- [LIVMS]-x(2)-C-x-C
Description
The apical membrane of many tight epithelia contains sodium channels that are primarily characterised by their high affinity to the diuretic blocker amiloride [MEDLINE:8905643]. These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis . 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 [MEDLINE: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 : 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 .
(Above description text is from InterPro entry IPR001873.)
From:
http://ca.expasy.org/cgi-bin/niceprot.pl?P37089:
TOPOLOGY:
MEDLINE=94230383;PubMed=8175716 [NCBI, ExPASy, EBI, Israel, Japan]
Renard S., Lingueglia E., Voilley N., Lazdunski M., Barbry P.;
"Biochemical analysis of the membrane topology of the amiloride-sensitive Na+ channel.";
J. Biol. Chem. 269:12981-12986(1994).
* FUNCTION: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride.
Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically)
through the apical membrane of epithelial cells. Controls the reabsorption of sodium in
kidney, colon, lung and sweat glands. Also plays a role in taste perception.
* SUBUNIT: Heterotetramer of two alpha, one beta and one gamma subunit. A delta subunit can replace
the alpha subunit. Interacts with the WW domains of NEDD4, WWP1 and WWP2 (By similarity).
* SUBCELLULAR LOCATION: Integral membrane protein; localized to the apical plasma membrane and
intracellular vesicles.
* PTM: Ubiquitinated; this targets individual subunits for proteasome-mediated degradation.
* SIMILARITY: Belongs to the amiloride-sensitive sodium channel family.
From PROSITE PS01206 (ASC):
Documentation
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 alpha, beta and gamma. A fourth subunit (delta) can replace the alpha 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.
Description of pattern(s) and/or profile(s)
Consensus pattern Y-x(2)-[EQTF]-x-C-x(2)-[GSTDNL]-C-x-[QT]-x(2)-[LIVMT]- [LIVMS]-x(2)-C-x-C
Epithelial sodium channel
Signatures [?] TIGR00859;ENaC (46 proteins)
Type [?] Family
Dates [?] 2001-11-01 10:46:59.0 (created)
Parent [?]
[tree] IPR001873; Na+ channel, amiloride-sensitive
Process [?] sodium ion transport (GO:0006814)
Function [?] amiloride-sensitive sodium channel activity (GO:0015280)
Component [?] integral to membrane (GO:0016021)
Abstract [?]
The epithelial Na+ channel (ENaC) proteins consist of sodium channels from animals and has no recognizable homologues in other eukaryotes or bacteria. The vertebrate ENaC proteins from epithelial cells cluster tightly together on the phylogenetic tree: voltage-insensitive ENaC homologues are also found in the brain. Eleven sequenced Caenorhabditis elegans proteins, including the degenerins (IPR004726), are distantly related to the vertebrate proteins as well as to each other.
At least some of the proteins in this group form part of a mechano-transducing complex for touch sensitivity. Others include the acid-sensing ion channels, ASIC1-3 that are homo- or hetero-oligomeric neuronal H+-gated channels that mediate pain sensation in response to tissue acidosis. Mammalian ENaC is important for the maintenance of Na+ balance and the regulation of blood pressure. Three homologous ENaC subunits, a, b and g, have been shown to assemble to form the highly Na+-selective channel.