Alternative titles; symbols
HGNC Approved Gene Symbol: KCNAB1
Cytogenetic location: 3q25.31 Genomic coordinates (GRCh38) : 3:156,118,211-156,539,138 (from NCBI)
The KCNAB1 gene encodes the beta-1 member of the 'shaker'-related family of voltage-gated potassium channels. The beta subunits (see also KCNAB2 601142 and KCNB3 604111) modulate the gating properties and amplitudes of the alpha-subunit potassium channels, such as KCNA1 (176260). '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. Voltage-activated, outwardly rectifying potassium channels (Kv) are heterooligomers that are assembled from alpha and beta subunits in a 1:1 molar ratio (summary by Schultz et al., 1996).
England et al. (1995) cloned a human heart cDNA encoding a beta subunit that they designated Kv-beta-1.3. Sequence analysis revealed that Kv-beta-1.3 and the previously identified human Kv-beta-1 (England et al., 1995) and Kv-beta-3 (McCormack et al., 1995) subunits differ only at their N termini and are encoded by alternatively spliced mRNAs from a single gene. The authors suggested that Kv-beta-1 and Kv-beta-3 be renamed Kv-beta-1.1 and Kv-beta-1.2, respectively. The predicted 419-amino acid Kv-beta-1.3 subunit does not contain a hydrophobic domain and is likely to be a cytoplasmic protein, like other beta subunits.
By Northern blot analysis, Leicher et al. (1996) found that the KCNA1B gene was expressed as 3.4- and 3.8-kb mRNAs in human brain. The pattern of expression of Kv1-alpha and Kv-beta subunits suggested an intricate and cell-specific regulatory mechanism that produces distinct combinations of alpha and beta subunits in different nuclei of the brain. The Kv-beta-1.1 and Kv-beta-1.2 splice variants contain an N-terminal inactivating domain similar to that found in A-type Kv channels (see KCNA4; 176266).
Leicher et al. (1996) and Leicher et al. (1998) reported that the KCNA1B open reading frame is composed of 14 exons spanning more than 380 kb. There are 3 alternative first exons encoding the divergent N termini of the 3 Kv-beta-1 isoforms.
Using a combination of PCR analysis of somatic cell hybrids and fluorescence in situ hybridization, Schultz et al. (1996) mapped the human KCNAB1 and KCNAB2 (601142) genes to chromosomes 3q26.1 and 1p36.3, respectively. The localization of KCNAB1 was corroborated by PCR screening of the CEPH YAC library.
By study of an intersubspecific backcross mapping panel, Jones et al. (1998) mapped the mouse Kcna1b gene to chromosome 3.
When coexpressed in Xenopus oocytes, England et al. (1995) found that the Kv-beta-1.3 subunit altered the functional properties of Kv1.5 (KCNA5; 176267), converting it from a delayed rectifier to a channel with rapid but partial inactivation. In addition, Kv-beta-1.3 converted the Kv1.5 outwardly rectifying current-voltage relationship to one showing strong inward rectification. England et al. (1995) concluded that Kv channel current diversity may arise from association with alternatively spliced Kv-beta subunits.
Leicher et al. (1996) also demonstrated that coexpression of Kv-beta-1.1 and Kv-beta-1.2 in mammalian cells conferred rapid inactivation on Kv1.5 channels, with different potencies.
In rat brain, Schulte et al. (2006) found that Lgi1 (604619) associated with Kcna1-containing channel complexes in presynaptic axon terminals. Functional studies showed that Lgi1 effectively and specifically prevented rapid voltage-gated potassium channel inactivation mediated by Kcnab1.
England, S. K., Uebele, V. N., Kodali, J., Bennett, P. B., Tamkun, M. M. A novel K+ channel beta-subunit (hKv-beta-1.3) is produced via alternative mRNA splicing. J. Biol. Chem. 270: 28531-28534, 1995. [PubMed: 7499366] [Full Text: https://doi.org/10.1074/jbc.270.48.28531]
England, S. K., Uebele, V. N., Shear, H., Kodali, J., Bennett, P. B., Tamkun, M. M. Characterization of a voltage-gated K+ channel beta subunit expressed in human heart. Proc. Nat. Acad. Sci. 92: 6309-6313, 1995. [PubMed: 7603988] [Full Text: https://doi.org/10.1073/pnas.92.14.6309]
Jones, J. M., Bentley, E., Meisler, M. H., Darling, S. M. Genetic mapping of the voltage-gated shaker potassium channel beta subunit Kcnab1 to mouse chromosome 3. Mammalian Genome 9: 260 only, 1998. [PubMed: 9501317] [Full Text: https://doi.org/10.1007/s003359900740]
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]
Leicher, T., Roeper, J., Weber, K., Wang, X., Pongs, O. Structural and functional characterization of human potassium channel subunit beta-1 (KCNA1B). Neuropharmacology 35: 787-795, 1996. [PubMed: 8938711] [Full Text: https://doi.org/10.1016/0028-3908(96)00133-5]
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]
Schulte, U., Thumfart, J.-O., Klocker, N., Sailre, C. A., Bildl, W., Biniossek, M., Dehn, D., Deller, T., Eble, S., Abbass, JK., Wangler, T., Knaus, H.-G., Fakler, B. The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv-beta-1. Neuron 49: 697-706, 2006. [PubMed: 16504945] [Full Text: https://doi.org/10.1016/j.neuron.2006.01.033]
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]