title: Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium.
abstract: 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.
mesh_terms: D000595:Amino Acid Sequence; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D015894:Genome, Human; D015698:Genomic Library; D006801:Humans; D008969:Molecular Sequence Data; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D050396:TRPP Cation Channels
chemical_list: D018076:DNA, Complementary; D011506:Proteins; D012333:RNA, Messenger; D050396:TRPP Cation Channels