Structure of human voltage-dependent calcium channel (VDCC) β3 subunit gene

Abstract

In excitable and endocrine organs, calcium influxes through the voltage-dependent calcium channel (VDCC), composed of four (α1, α2, β, and δ) subunits. Four isoforms of beta subunits (β1, β2, β3, β4) are known to exist. The cytoplasmic β subunits regulate the channel activity by accelerating the kinetics of activation and inactivation through phosphorylation. Regulation of calcium channel activities are also provided by alternative splicing of the β subunits. To elucidate the genomic organization of the VDCC β3 subunit gene, two genomic clones were isolated from human genomic liabrary using the whole rat cDNA for β3 subunit as a probe. The β3 subunit gene in lamda phage DNA was analyzed by Southern hybridization and sequencing. A 19.1 kb clone (2BHG13) contained the whole β3 cDNA sequence, consisting at least 14 exons. The deduced amino acid sequence from the exons shows 97% similarity with that of rat gene. Two alternatively spliced forms of β3 subunit at 5'-end were found. The β3 subunit had many possible phosphorylation sites. Alternative splicing of β3 subunit mRNA at 5'-end and phosphorylation of the β3 subunit protein may play a regulatory role in calcium influxes.