Alternative titles; symbols
HGNC Approved Gene Symbol: KCNAB2
Cytogenetic location: 1p36.31 Genomic coordinates (GRCh38): 1:5,992,676-6,101,180 (from NCBI)
'Shaker' and other voltage-dependent potassium channel proteins help to determine the electrical properties of excitable cells and play additional physiologic roles in nonexcitable cell types. See KCNA1 (176260). Mammalian Shaker potassium channel alpha subunits associate with cytoplasmic beta subunits that modulate the inactivation of the channel. The beta subunits belong to a superfamily of NAD(P)H-dependent enzymes, suggesting that they may be involved in additional physiologic processes. Shaker potassium channel complexes are thought to be composed of 4 alpha and 4 beta subunits.
By PCR of a human hippocampal library with degenerate primers based on conserved regions of rat beta-1 (KCNA1B; 601141) and beta-2 subunits, McCormack et al. (1995) isolated cDNAs encoding human beta-1 and beta-2. The predicted 367-amino acid human, bovine, and rat beta-2 subunits are 99% identical. Unlike beta-1, the beta-2 subunit does not contain an N-terminal inactivation 'ball' domain. Instead, functional studies of beta-2 expressed in Xenopus oocytes indicated that it increased the rate of the endogenous Kv1.4 alpha subunit (176266) inactivation process.
Leicher et al. (1998) reported that the KCNA2B gene contains 15 exons and spans approximately 70 kb. The exon/intron structure of KCNA2B is comparable to that of KCNA1B and KCNA3B (604111), although the size of the introns varies significantly among the genes.
By analysis of somatic cell hybrids and by FISH, Schultz et al. (1996) mapped the KCNA2B gene to 1p36.3.
The results of Gong et al. (1999) suggested that ZIP, the rat homolog of p62 (601530), acts as a link that targets the activity of Kv-beta-2 and PKC-zeta (176982).
Gu et al. (2003) found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 (186940) or dendritic transferrin receptor (TFR; 190010), Kv1 T1 domains promoted their axonal surface expression. Moreover, mutations in the T1 domain of Kv1.2 (176262) that eliminated association with Kv-beta-2 compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. The authors concluded that proper association of Kv-beta with the Kv1 T1 domain is essential for axonal targeting.
McCormack et al. (2002) developed Kv-beta-2-null mice and mice carrying a tyr90-to-phe (Y90F) mutation in the putative aldo-keto reductase (103880)-like catalytic domain of Kv-beta-2. Null mice showed reduced life spans, occasional seizures, and cold swim-induced tremors, a phenotype similar to that observed in Kv1.1-null mice. In Kv-beta-2-null mice, Kv1.1 and Kv1.2 localized normally in cerebellar basket cell terminals and the juxtaparanodal region of myelinated nerves, suggesting that Kv-beta-2 does not have a chaperone-like function. Mice expressing the Y90F mutation had no overt phenotype.
Gong, J., Xu, J., Bezanilla, M., van Huizen, R., Derin, R., Li, M. Differential stimulation of PKC phosphorylation of potassium channels by ZIP1 and ZIP2. Science 285: 1565-1569, 1999. [PubMed: 10477520] [Full Text: https://doi.org/10.1126/science.285.5433.1565]
Gu, C., Jan, Y. N., Jan, L. Y. A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels. Science 301: 646-649, 2003. [PubMed: 12893943] [Full Text: https://doi.org/10.1126/science.1086998]
Leicher, T., Bahring, R., Isbrandt, D., Pongs, O. Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J. Biol. Chem. 273: 35095-35101, 1998. [PubMed: 9857044] [Full Text: https://doi.org/10.1074/jbc.273.52.35095]
McCormack, K., Connor, J. X., Zhou, L., Ho, L. L., Ganetzky, B., Chiu, S.-Y., Messing, A. Genetic analysis of the mammalian K(+) channel beta subunit Kv-beta-2 (Kcnab2). J. Biol. Chem. 277: 13219-13228, 2002. [PubMed: 11825900] [Full Text: https://doi.org/10.1074/jbc.M111465200]
McCormack, K., McCormack, T., Tanouye, M., Rudy, B., Stuhmer, W. Alternative splicing of the human Shaker K+ channel beta-1 gene and functional expression of the beta-2 gene product. FEBS Lett. 370: 32-36, 1995. [PubMed: 7649300] [Full Text: https://doi.org/10.1016/0014-5793(95)00785-8]
Schultz, D., Litt, M., Smith, L., Thayer, M., McCormack, K. Localization of two potassium channel beta subunit genes, KCNA1B and KCNA2B. Genomics 31: 389-391, 1996. [PubMed: 8838324] [Full Text: https://doi.org/10.1006/geno.1996.0065]