THE POLYCYSTIC KIDNEY-DISEASE-1 (PKD1) GENE ENCODES A NOVEL PROTEIN WITH MULTIPLE CELL RECOGNITION DOMAINS

Characterization of the polycystic kidney disease 1 (PKD1) gene has be en complicated by genomic rearrangements on chromosome 16. We have use d an exon linking strategy, taking RNA from a cell line containing PKD 1 but not the duplicate loci, to clone a cDNA contig of the entire tra nscript. The transcript consists of 14,148 bp (including a correction to the previously described C terminus), distributed among 46 exons sp anning 52 kb. The predicted PKD1 protein, polycystin, is a glycoprotei n with multiple transmembrane domains and a cytoplasmic C-tail. The N- terminal extracellular region of over 2,500 aa contains leucine-rich r epeats, a C-type lectin, 16 immunoglobulin-like repeats and four type III fibronectin-related domains. Our results indicate that polycystin is an integral membrane protein involved in cell-cell/matrix interacti ons.