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PROSITE documentation PDOC50912EAR repeat profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC50912
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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Mulley J.C. Scheffer I.E. Petrou S. Berkovic S.F. |
| Title | Channelopathies as a genetic cause of epilepsy. | |
| Source | Curr. Opin. Neurol. 16:171-176(2003). | |
| PubMed ID | 12644745 | |
| DOI | 10.1097/01.wco.0000063767.15877.c7 |
| 2 | Authors | Scheel H. Tomiuk S. Hofmann K. |
| Title | A common protein interaction domain links two recently identified epilepsy genes. | |
| Source | Hum. Mol. Genet. 11:1757-1762(2002). | |
| PubMed ID | 12095917 |
| 3 | Authors | Staub E. Perez-Tur J. Siebert R. Nobile C. Moschonas N.K. Deloukas P. Hinzmann B. |
| Title | The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. | |
| Source | Trends Biochem. Sci. 27:441-444(2002). | |
| PubMed ID | 12217514 |
| 4 | Authors | Fertig E. Lincoln A. Martinuzzi A. Mattson R.H. Hisama F.M. |
| Title | Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features. | |
| Source | Neurology 60:1687-1690(2003). | |
| PubMed ID | 12771268 |
| 5 | Authors | Skradski S.L. Clark A.M. Jiang H. White H.S. Fu Y.H. Ptacek L.J. |
| Title | A novel gene causing a mendelian audiogenic mouse epilepsy. | |
| Source | Neuron 31:537-544(2001). | |
| PubMed ID | 11545713 |
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