title: Identification of two novel polycystic kidney disease-1-like genes in human and mouse genomes.
abstract: Mutations to the prototypical members of the two general classes of polycystins, polycystin-1 encoded by PKD1 and polycystin-2 encoded by PKD2, underlie autosomal-dominant polycystic kidney disease. Here we report the identification of a pair of genes homologous to PKD1 from both the human and mouse genomes. PKD1L2 and PKD1L3 are located on human chromosome 16q22-q23 and mouse chromosome 8 and are alternatively spliced. The human and mouse forms of PKD1L2 are highly conserved, with each one consisting of 43 exons and approximately 2,460 codons. PKD1L3 shows regional sequence divergence, with the mouse form having two additional exons and a much larger exon 5. The predicted protein products of PKD1L2 and PKD1L3 contain the combination of GPS and PLAT/LH2 domains that uniquely define them as polycystin-1 family members. They are predicted to have 11 membrane-spanning regions with a large extracellular domain consistent with the proposed receptor function of this protein family. PKD1L2 and PKD1L3 contain strong ion channel signature motifs that suggest their possible function as components of cation channel pores. Polycystin-1-related proteins may not only regulate channels, but may actually be part of the pore-forming unit.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Airong
authors.initials: A
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Si-Wook
authors.initials: SW
authors.lastname: Sung
authors.forename: Stefan
authors.initials: S
authors.lastname: Somlo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002875:Chromosomes; D005091:Exons; D016678:Genome; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D007690:Polycystic Kidney Diseases / Q000209:etiology / Q000235:genetics*; D017434:Protein Structure, Tertiary; D017385:Sequence Homology; D040681:Structural Homology, Protein; D014018:Tissue Distribution
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins