Polycystic kidney disease: the complete structure of the PKD1 gene and its protein

International Polycystic Kidney Disease Consortium - Cell, 1995 - Elsevier
International Polycystic Kidney Disease Consortium
Cell, 1995Elsevier
Mutations in the PKD1 gene are the most common cause of autosomal dominant polycystic
kidney disease (ADPKD). Other PKD1-like loci on chromosome 16 are approximately 97%
identical to PKD1. To determine the authentic PKD1 sequence, we obtained the genomic
sequence of the PKD1 locus 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 novel
domain architecture. The amino-terminal half of the protein consists of a mosaic of …
Mutations in the PKD1 gene are the most common cause of autosomal dominant polycystic kidney disease (ADPKD). Other PKD1-like loci on chromosome 16 are approximately 97% identical to PKD1. To determine the authentic PKD1 sequence, we obtained the genomic sequence of the PKD1 locus 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 novel domain architecture. The amino-terminal half of the protein consists of a mosaic of previously described domains, including leucine-rich repeats flanked by characteristic cysteine-rich structures, LDL-A and 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 involved in adhesive protein-protein and protein-carbohydrate interactions in the extracellular compartment. We propose a hypothesis that links the predicted properties of the protein with the diverse phenotypic features of ADPKD.
Elsevier