POLYCYSTIC KIDNEY-DISEASE - THE COMPLETE STRUCTURE OF THE PKD1 GENE AND ITS PROTEIN

Mutations in the PKD1 gene sire the most common cause of autosomal dom inant polycystic kidney disease (ADPKD). Other PKD1-like loci on chrom osome 16 are approximately 97% identical to PKD1. To determine the aut hentic PKD1 sequence, we obtained the genomic sequence of the PKD1 loc us and assembled a PKD1 transcript from the sequence of 46 exons. The 14.5 kb PKD1 transcript encodes a 4304 amino acid protein that has a n ovel domain architecture. The amino-terminal half of the protein consi sts of a mosaic of previously described domains, including leucine-ric h repeats flanked by characteristic cysteine-rich structures, LDL-A an d C-type lectin domains, and 14 units of a novel 80 amino acid domain. The presence of these domains suggests that the PKD1 protein is invol ved in adhesive protein-protein and protein-carbohydrate interactions in the extracellular compartment. We propose a hypothesis that links t he predicted properties of the protein with the diverse phenotypic fea tures of ADPKD.