Cloning and characterization of the human retina-specific gene MPP4, a novel member of the p55 subfamily of MAGUK proteins

To identify novel retina-specific genes systematically, we are performing e xpression profiling of retina ESTs that have been assembled in the human Un iGene clusters, In this study, we report the 2619-bp full-length cDNA cloni ng and genomic organization of a gene corresponding to an EST cluster that was demonstrated to be exclusively present in retinal tissue. Alignment of the deduced amino acid sequence to sequence from protein databases revealed this gene, termed MPP4, to be a member of the membrane-associated guanylat e kinase (MAGUK) protein family. It consists of 637 amino acids and contain s the characteristic MAGUK motifs: an N-terminal PDZ domain, a central src homology 3 region (SH3), and a C-terminal guanylate kinase-like (GUK) domai n. Due to the presence of only one PDZ motif, MPP4 is part of the p55 subfa mily, named after the major palmitoylated erythrocyte membrane protein p55/ MPP1. MAGUK proteins serve as molecular scaffolds to coordinate the membran e-associated cytoskeleton, ion channel and receptor clustering, signaling p athways, and the formation of cellular junctions, The abundant expression o f MPP4 in the human retina suggests an important but so far unknown functio n in this tissue. Colocalization of MPP4 and autosomal recessive retinitis pigmentosa 26 (RP26) on chromosome 2q31-q33 makes this transcript an attrac tive candidate for the disease gene. (C) 2001 Academic Press.