Alternative titles; symbols
HGNC Approved Gene Symbol: CACNB3
Cytogenetic location: 12q13.12 Genomic coordinates (GRCh38): 12:48,814,480-48,828,941 (from NCBI)
Collin et al. (1994) isolated the beta subunit of a human voltage-dependent calcium channel gene from a 9-week-old human total-embryo cDNA library. The gene encodes a 482-amino acid polypeptide with a predicted mass of 54,571 kD. The gene, called H beta 3 by them, was expressed mostly in brain, smooth muscle, and ovary.
Yamada et al. (1995) described the exon-intron structure of the CACNLB3 gene, which spans approximately 8 kb and comprises 13 exons.
Collin et al. (1994) localized the CACNB3 gene to chromosome 12q13 by fluorescence in situ hybridization.
To elucidate the molecular mechanism of the interaction between calcium channel alpha-1 (see 601011) and beta subunits, Chen et al. (2004) determined the crystal structures of the conserved core region of beta-3 (CACNB3), alone and in complex with the alpha-interaction domain (AID), and of beta-4 (CACNB4; 601949) alone. The structures showed that the beta subunit core contains 2 interacting domains: a Src homology 3 (SH3) domain and a guanylate kinase domain. The AID binds to a hydrophobic groove in the guanylate kinase domain through extensive interactions, conferring extremely high affinity between alpha-1 and beta subunits. The beta-interaction domain (BID) is essential both for the structural integrity of and for bridging the SH3 and guanylate kinase domains, but it does not participate directly in binding alpha-1.
Lory et al. (1997) provided a unified nomenclature for voltage-gated calcium channel genes (see 114207), tabulated 12 of these genes, and gave the map location of each.
Murakami et al. (2002) noted that the accessory beta-3 subunits of calcium channels are preferentially associated with the alpha-1b subunit (CACNA1B; 601012) in neuronal N-type channels. By gene targeting, they deleted the beta-3 subunit in mice and found that the mutation dampened the processing of painful stimuli, specifically pain induced by chemical inflammation. The ascending pain pathways of the spinal cord showed altered N-type channel activity. In vitro binding studies and pharmacologic manipulation indicated reduced expression of alpha-1b subunits in dorsal root ganglion (DRG) neurons. Murakami et al. (2002) concluded that, since beta-3 controls the membrane targeting of alpha-1 subunits, the loss of beta-3 reduced the number of N-type calcium channels present in the membranes of DRG neurons and dampened their response to inflammatory stimuli.
Berggren et al. (2004) found that Cacnb3 -/- mice showed a more efficient glucose homeostasis compared with wildtype mice due to increased glucose-stimulated insulin secretion. The increased insulin secretion resulted from increased glucose-induced cytoplasmic free Ca(2+) concentration oscillation frequency in Cacnb3 -/- beta cells, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca(2+) mobilization from intracellular stores. Berggren et al. (2004) concluded that CACNB3 negatively modulates InsP3-induced Ca(2+) release without affecting the function of the voltage-gated L-type Ca(2+) channel.
Berggren, P.-O., Yang, S.-N., Murakami, M., Efanov, A. M., Uhles, S., Kohler, M., Moede, T., Fernstrom, A., Appelskog, I. B., Aspinwall, C. A., Zaitsev, S. V., Larsson, O., and 11 others. Removal of Ca(2+) channel beta-3 subunit enhances Ca(2+) oscillation frequency and insulin exocytosis. Cell 119: 273-284, 2004. [PubMed: 15479643] [Full Text: https://doi.org/10.1016/j.cell.2004.09.033]
Chen, Y., Li, M., Zhang, Y., He, L., Yamada, Y., Fitzmaurice, A., Shen, Y., Zhang, H., Tong, L., Yang, J. Structural basis of the alpha-1-beta subunit interaction of voltage-gated Ca(2+) channels. Nature 429: 675-680, 2004. [PubMed: 15170217] [Full Text: https://doi.org/10.1038/nature02641]
Collin, T., Lory, P., Taviaux, S., Courtieu, C., Guillbault, P., Berta, P., Nargeot, J. Cloning, chromosomal location and functional expression of the human voltage-dependent calcium-channel beta 3 subunit. Europ. J. Biochem. 220: 257-262, 1994. [PubMed: 8119293] [Full Text: https://doi.org/10.1111/j.1432-1033.1994.tb18621.x]
Lory, P., Ophoff, R. A., Nahmias, J. Towards a unified nomenclature describing voltage-gated calcium channel genes. Hum. Genet. 100: 149-150, 1997. [PubMed: 9254840] [Full Text: https://doi.org/10.1007/s004390050481]
Murakami, M., Fleischmann, B., De Felipe, C., Freichel, M., Trost, C., Ludwig, A., Wissenbach, U., Schwegler, H., Hofmann, F., Hescheler, J., Flockerzi, V., Cavalie, A. Pain perception in mice lacking the beta-3 subunit of voltage-activated calcium channels. J. Biol. Chem. 277: 40342-40351, 2002. [PubMed: 12161429] [Full Text: https://doi.org/10.1074/jbc.M203425200]
Yamada, Y., Masuda, K., Li, Q., Ihara, Y., Kubota, A., Miura, T., Nakamura, K., Fujii, Y., Seino, S., Seino, Y. The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes. Genomics 27: 312-319, 1995. [PubMed: 7557998] [Full Text: https://doi.org/10.1006/geno.1995.1048]