PROSITE documentation PDOC50912
EAR repeat profile


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 β-strands) and the numbers of repeated copies (seven) suggest that the EAR domain belongs to the β-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.

Last update:

January 2018 / Profile and text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

EAR, PS50912; EAR repeat profile  (MATRIX)


1AuthorsMulley J.C. Scheffer I.E. Petrou S. Berkovic S.F.
TitleChannelopathies as a genetic cause of epilepsy.
SourceCurr. Opin. Neurol. 16:171-176(2003).
PubMed ID12644745

2AuthorsScheel H. Tomiuk S. Hofmann K.
TitleA common protein interaction domain links two recently identified epilepsy genes.
SourceHum. Mol. Genet. 11:1757-1762(2002).
PubMed ID12095917

3AuthorsStaub E. Perez-Tur J. Siebert R. Nobile C. Moschonas N.K. Deloukas P. Hinzmann B.
TitleThe novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders.
SourceTrends Biochem. Sci. 27:441-444(2002).
PubMed ID12217514

4AuthorsFertig E. Lincoln A. Martinuzzi A. Mattson R.H. Hisama F.M.
TitleNovel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features.
SourceNeurology 60:1687-1690(2003).
PubMed ID12771268

5AuthorsSkradski S.L. Clark A.M. Jiang H. White H.S. Fu Y.H. Ptacek L.J.
TitleA novel gene causing a mendelian audiogenic mouse epilepsy.
SourceNeuron 31:537-544(2001).
PubMed ID11545713

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