title: Identification of a novel protein interacting with laforin, the EPM2a progressive myoclonus epilepsy gene product.
abstract: We have identified an interacting partner protein (encoded by the human EPM2AIP1 gene (approved symbol)) for laforin, the product of the EPM2A gene, which is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The EPM2AIP1 gene was identified in a screen for laforin-interacting proteins with a human brain cDNA library using the yeast two-hybrid system. The specificity of the interaction was confirmed by coimmunoprecipitation of in vivo-transfected protein and by using EPM2A deletion constructs. Subcellular colocalization of laforin and EPM2AIP1 protein was also demonstrated. The human EPM2AIP1 gene, corresponding to the KIAA0766 cDNA clone in the databases, was characterized and shown, like EPM2A, to be ubiquitously expressed. The gene, which comprises one large exon 1824 nucleotides in length and has alternative 3' untranslated regions, maps to human chromosome 3p22.1. The function is currently not known and extensive analyses do not reveal any homology to other proteins or any obvious structural motifs. Because genetic heterogeneity in Lafora disease has been described, mutational analysis of the EPM2AIP1 gene was performed on non-EPM2A patients, but no mutations were found. The identification of this first binding partner for laforin promises to be an important step toward unraveling the underlying pathogenesis of this severest form of teenage-onset epilepsy.
authors.affiliation: Department of Genetics, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Leonarda
authors.initials: L
authors.lastname: Ianzano
authors.forename: Xiao C
authors.initials: XC
authors.lastname: Zhao
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D000595:Amino Acid Sequence; D001921:Brain; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002893:Chromosomes, Human, Pair 3; D004252:DNA Mutational Analysis; D040461:Gene Components; D015723:Gene Library; D006801:Humans; D020192:Lafora Disease / Q000209:etiology / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; C483189:EPM2AIP1 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human