Genomic Organization of Human β3 Subunit Gene of Voltage-Gated Calcium Channel

Voltage-gated calcium channel (VGCC) is composed of at least four (α1, α2, β, and δ)subunits. Among them β subunit accelerates the kinetics of activation (channel opening) and nactivation (channel closure), and reguates the channel activity by phosphprylation through PKAand PKC that are activated by various signal transduction mechanisms. Until recently four isoforms of beta subunits (β1, β2, β3, β4) have been identified. Our recent data shows that VDCCβ3 gene is expressed only in e nervous system and around the perinatal stage at high level.Alternative splicing was o observed at both 5'- and 3'- ends. To elucidate alternative splicingand cts-acting element of gene regulation of the β3 subunit gene we isolated a 12.5kb-sizedgenomic clone encompassing β3 subunit gene from human genomic library using the whole β3subunit cDNA from NG108-l5 cell line as a probe. The genome was analyzed by Southem hybridization and sequencing. The β3 subunit gene consists at least of 12 exons, and deduced amino acid sequence from the exons showed 98% similarity with that of rat gene. The β3 subunitgene is not alternatively spliced at the middle of the gene, and has many possible phosphorylation sites,which may confer the regulatory role of the β3 subunit gene.