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.