{PDOC50912}
{PS50912; EAR}
{BEGIN}
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* EAR repeat profile *
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Most  of  the  hereditary  idiopathic  epilepsies  are  due to mutation in ion
channels  expressed  in brain [1]. Recently two non-ion channel genes LGI1 and
VGLR1 have emerged as important causes of specific epilepsy syndromes [1]. The
product of these two genes share a conserved repeated region of about 44 amino
acid residues, the EAR repeat (for epilepsy-associated repeat), which has also
been called the Epitempin (EPTP) repeat. The EAR repeats tend to be present in
seven copies per proteins [2,3].

The  predicted  secondary  structure  (four  beta-strands)  and the numbers of
repeated   copies   (seven)   suggest  that  the  EAR  domain  belongs to  the
beta-propeller  fold.  A  common functional feature found in all characterized
domains  of  this  class  is  a participation in protein-protein interactions.
Since  the EAR repeat is found in the ectodomain of VLGR1, it is most probably
involved in ligand recognition by the receptor [2,3].

Proteins known to contain EAR repeats are listed below:

 - Mammalian  LGI1  to  LGI4.  LGI1  is  mutated in autosomal dominant partial
   epilepsy  with  auditory  features (ADPEAF). The F348C missense mutation is
   located in the third EAR repeat (7 copies) [4].
 - Mammalian  thrombo-spondin  N-terminal  domain  and  EAR repeats containing
   protein (TSPEAR) (7 copies).
 - Mammalian  very  large  G  protein-coupled  receptor 1 (VGLR1) or monogenic
   audiogenic  seizure-susceptible  (MASS1)  protein.  In  mouse, mutations in
   MASS1  gene  are  associated  with  generalized  epilepsy  and  seizures in
   response to loud noises (7 copies) [5].

The profile we developed covers the whole EAR repeat.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2018 / Profile and text revised.

[ 1] Mulley J.C., Scheffer I.E., Petrou S., Berkovic S.F.
     "Channelopathies as a genetic cause of epilepsy."
     Curr. Opin. Neurol. 16:171-176(2003).
     PubMed=12644745; DOI=10.1097/01.wco.0000063767.15877.c7
[ 2] Scheel H., Tomiuk S., Hofmann K.
     "A common protein interaction domain links two recently identified
     epilepsy genes."
     Hum. Mol. Genet. 11:1757-1762(2002).
     PubMed=12095917
[ 3] Staub E., Perez-Tur J., Siebert R., Nobile C., Moschonas N.K.,
     Deloukas P., Hinzmann B.
     "The novel EPTP repeat defines a superfamily of proteins implicated in
     epileptic disorders."
     Trends Biochem. Sci. 27:441-444(2002).
     PubMed=12217514
[ 4] Fertig E., Lincoln A., Martinuzzi A., Mattson R.H., Hisama F.M.
     "Novel LGI1 mutation in a family with autosomal dominant partial
     epilepsy with auditory features."
     Neurology 60:1687-1690(2003).
     PubMed=12771268
[ 5] Skradski S.L., Clark A.M., Jiang H., White H.S., Fu Y.H., Ptacek L.J.
     "A novel gene causing a mendelian audiogenic mouse epilepsy."
     Neuron 31:537-544(2001).
     PubMed=11545713

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