{PDOC00926}
{PS01206; ASC}
{BEGIN}
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* Amiloride-sensitive sodium channels signature *
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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.

-Consensus pattern: Y-x(2)-[EQTFPMSI]-x-C-x(3)-C-x-[QTAVKS]-x(2)-[LIVMT]-
                    [LIVMSAQ]-x(2)-C-x-C
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2006 / Pattern revised.

[ 1] Garty H.
     "Molecular properties of epithelial, amiloride-blockable Na+
     channels."
     FASEB J. 8:522-528(1994).
     PubMed=8181670
[ 2] Jentsch T.J.
     "Trinity of cation channels."
     Nature 367:412-413(1994).
     PubMed=7509038; DOI=10.1038/367412a0
[ 3] Le T., Saier M.H. Jr.
     "Phylogenetic characterization of the epithelial Na+ channel (ENaC)
     family."
     Mol. Membr. Biol. 13:149-157(1996).
     PubMed=8905643
[ 4] Garcia-Anoveros J., Ma C., Chalfie M.
     Curr. Biol. 5:441-448(1995).
[ 5] Waldmann R., Champigny G., Bassilana F., Voilley N., Lazdunski M.
     "Molecular cloning and functional expression of a novel
     amiloride-sensitive Na+ channel."
     J. Biol. Chem. 270:27411-27414(1995).
     PubMed=7499195
[ 6] Snyder P.M., McDonald F.J., Stokes J.B., Welsh M.J.
     "Membrane topology of the amiloride-sensitive epithelial sodium
     channel."
     J. Biol. Chem. 269:24379-24383(1994).
     PubMed=7929098

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