CLONING AND CHARACTERIZATION OF THE HUMAN HOMOLOG OF A DYSTROPHIN-RELATED PHOSPHOPROTEIN FOUND AT THE TORPEDO ELECTRIC ORGAN POSTSYNAPTIC MEMBRANE

Dystrophin is the protein product which is absent in Duchenne muscular dystrophy (DMD), In mammalian skeletal muscle, dystrophin is found in association with several integral and peripheral membrane proteins, f orming a complex known as the dystrophin glycoprotein complex (DGC). I n an expressed sequence tag (EST) database search to identify new dyst rophin related genes, we isolated EST00891 which showed 57% homology t o the cysteine-rich domain of dystrophin and localized to 18q12.1-12.2 . This EST is also highly homologous (90%) to the Torpedo californica post-synaptic 87 kDa phosphoprotein, Screening human adult brain and s keletal muscle cDNA libraries with this EST resulted in cloning multip le cDNAs which encode several splice forms all homologous to the C-ter minal domain of dystrophin. The largest open reading frame isolated sh ows 94% homology (86% identity) to the Torpedo 87 kDa protein and 50% homology to the cysteine-rich and carboxy-terminal domains of dystroph in. The other cDNAs isolated encode smaller splice forms of this gene which we have named dystrobrevin. The tissue distribution of dystrobre vin mRNA shows five distinct transcripts which are preferentially expr essed between different tissues. In addition, antibodies against eithe r the Torpedo 87 kDa protein or human dystrobrevin demonstrate that at least three of the splice forms are translated as proteins in human b rain tissue extracts.