title: Structural characterization and promoter analysis of human potassium channel Kv8.1 (KCNV1) gene.
abstract: The voltage-gated K(+) channel (Kv) family comprises four subfamilies: Kv1, Kv2, Kv3 and Kv4. Kv6, Kv7, Kv8 and Kv9 subfamilies have also recently been reported. The gene for Kv8.1 (KCNV1) maps onto chromosome 8q23.3, a locus for benign adult familial myoclonic epilepsy. Despite sequence identity with other K(+) channel genes, KCNV1 does not display K(+) channel activity when expressed in Xenopus oocytes, instead inhibiting activity of Kv2 and Kv3 channels. The present study investigated the molecular structure of KCNV1. In silico analysis detected a new 5' noncoding exon, which extended the reported cDNA sequence to approximately 600 bp. A promoter motif was found only in the upstream region of the newly detected exon 1. To determine the transcriptional mechanism of KCNV1, we generated a series of deletion mutants and random mutants, and examined promoter activities using the luciferase system. Three Sp1 motifs were found to be active in the core promoter sequence, spanning from nt -1350 to -911 (A of the ATG initiation codon was counted as +1). At least two additional sequences were detected as essential elements for promoter activity. A possible alternative 3' end was also detected at 280 bp downstream from the reported 3' end. These results provide useful information in developing KCNV1 screening for epileptic disease.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ebihara
authors.forename: Hisako
authors.initials: H
authors.lastname: Ohba
authors.forename: Mika
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D005796:Genes / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: C120777:KCNV1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D008156:Luciferases