Structure of human voltage-dependent calcium channel (VDCC) beta 3 subunit gene

ABSTRACT

In excitable and endocrine organs, calcium influxes through the voltage-dependent calcium channel (VDCC), composed of four (alpha 1, alpha 2, beta, and gamma) subunits. Four isoforms of beta subunits (beta 1, beta 2, beta 3, beta 4) are known to exist, The cytoplasmic beta 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 beta subunits. To elucidate the genomic organization of the VDCC beta 3 subunit gene, two genomic clones were isolated from human genomic liabrary using the whole rat cDNA for beta 3 subunit as a probe. The beta 3 subunit gene in lamda phage DNA was analyzed by Southern hybridization and sequencing. A 19.1 kb clone (2BHG13) contained the whole beta 3 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 beta 3 subunit at 5'-end were found. The beta 3 subunit had many possible phosphorylation sites. Alternative splicing of beta 3 subunit mRNA at 5'-end and phosphorylation of the beta 3 subunit protein may play a regulatory role in calcium influxes.