title: Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects.
abstract: Polycystin-1 and polycystin-2 are the products of PKD1 and PKD2, genes that are mutated in most cases of autosomal dominant polycystic kidney disease. Polycystin-2 shares approximately 46% homology with pore-forming domains of a number of cation channels. It has been suggested that polycystin-2 may function as a subunit of an ion channel whose activity is regulated by polycystin-1. Here we report the identification of a human gene, PKDL, which encodes a new member of the polycystin protein family designated polycystin-L. Polycystin-L has 50% amino acid sequence identity and 71% homology to polycystin-2 and has striking sequence and structural resemblance to the pore-forming alpha1 subunits of Ca2+ channels, suggesting that polycystin-L may function as a subunit of an ion channel. The full-length transcript of PKDL is expressed at high levels in fetal tissues, including kidney and liver, and down-regulated in adult tissues. PKDL was assigned to 10q24 by fluorescence in situ hybridization and is linked to D10S603 by radiation hybrid mapping. There is no evidence of linkage to PKDL in six ADPKD families that are unlinked to PKD1 or PKD2. The mouse homologue of PKDL is deleted in Krd mice, a deletion mutant with defects in the kidney and eye. We propose that PKDL is an excellent candidate for as yet unmapped cystic diseases in man and animals.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: A E
authors.initials: AE
authors.lastname: Turco
authors.forename: Y
authors.initials: Y
authors.lastname: Pei
authors.forename: L
authors.initials: L
authors.lastname: Kalaydjieva
authors.forename: T
authors.initials: T
authors.lastname: Schiavello
authors.forename: S
authors.initials: S
authors.lastname: Weremowicz
authors.forename: W
authors.initials: W
authors.lastname: Ji
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
authors.forename: M
authors.initials: M
authors.lastname: Meisler
authors.forename: S T
authors.initials: ST
authors.lastname: Reeders
authors.forename: J
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007473:Ion Channels / Q000737:chemistry; D007668:Kidney / Q000473:pathology*; D008126:Lod Score; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D012160:Retina / Q000473:pathology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D050396:TRPP Cation Channels
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; C117185:PKD2L1 protein, human; C486487:Pkd2l1 protein, mouse