BKβ2
Description: potassium large conductance calcium-activated channel, subfamily M, beta member 2 Gene: Kcnmb2 Alias: Kcmb2, Kcnmb2, BKB2
Until 1999, only one beta subunit of BK (MaxiK) channels was known at the molecular level. This subunit (now known as the Beta-1-subunit) accounted mainly for MaxiK properties in vascular smooth muscle cells (VSMCs), where it is highly expressed. In the following years, three more beta subunits have been cloned and characterized. (Orio [540])
KCNMB2 (also known as MGC22431) encodes the beta2 subunit of BK (MaxiK) channels. MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. b2 is an auxiliary beta subunit which decreases the activation time of MaxiK alpha subunit currents. Two variants encoding the same protein have been found for this gene.
http://www.ncbi.nlm.nih.gov/gene/10242
Sequence similarities are major between b1-b2 and b2-b3, respectively. b4 is the most distantly related of all b-subunits. b-Subunit orthologs have not been described in Drosophila or in the worm C. elegans, suggesting that this protein is a “novel” acquisition in evolution. (Orio [540])
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_181361.3 | 2543 | |
| Mouse | NM_028231.2 | 2947 | |
| Rat | NM_176861.1 | 708 |
Protein Isoforms
Isoforms
Post-Translational Modifications
The topology of alpha and beta subunits that make up BK channels can be seen in fig. 1 of Orio [540]. The channel is formed by 4 alpha-subunits and probably 4 beta subunits. Regulatory beta subunits share a putative membrane topology, with two transmembrane segments connected by a 120- residue extracellular “loop” and with NH2 and COOH termi- nals oriented toward the cytoplasm (Fig. 1 [540]). The loop has three or four putative glycosylation sites. Four beta subunits have been cloned in mammals (Brenner [1181], Knaus [1167], Uebele [1179], Xia [1182]). The most notorious difference from b2 to the b1-subunit is an NH2- terminal domain that contains a hydrophobic region followed by positively charged residues. This type of sequence is characteristic of inactivation peptides that can occlude the conduction pathway of Shaker K+ and of MaxiK channels. (Orio [540])
BKβ2 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Ca2+ sensitivity and gating kinetics of channels formed by alpha- and b2-subunits are similar to those of channels formed by alpha- and b1-subunits (Xia [1182]).
b2 subunit is expressed preferentially in chromaffin cells and brain (Xia [11]](#a1182)).
In In rat chromaffin cells, there is a cell population that has inactivating MaxiK currents (MaxiKi) and a population with noninactivating MaxiK currents (MaxiKs) (Vergara [1100]). In the MaxiKi cells, the b2-subunit is expressed. As a consequence, MaxiK channels in these cells show rapid inactivation and slow deactivation kinetics (Xia [1182]). Because of the much slower deactivation of the MaxiK channel, the afterhyperpolarization phase is prolonged. This relieves Na+ channel inactivation and allows repetitive firing. Thus while MaxiKi are tonically firing cells, MaxiKs are phasically firing cells (Fig. 3 in [540], Solaro [1183]).
Coexpression of alpha- and b2-subunits produces inactivating currents, such as those seen in some chromaffin cells ( Orio [540]). Removal of the NH2-terminal domain, either by trypsin or molecular biology techniques, results in a b-subunit that does not inactivate the channel, so the currents are sustained and more suitable for kinetic and Ca2+ sensitivity comparisons. In contrast to the b1 subunit, the b2 subunit confers low CTX affinity compared with channels formed only by alpha-subunits (Xia [1182]).
References
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Endocytic trafficking signals in KCNMB2 regulate surface expression of a large conductance voltage and Ca(2+)-activated K+ channel.
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Structural determinants for functional coupling between the beta and alpha subunits in the Ca2+-activated K+ (BK) channel.
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Inactivation of BK channels by the NH2 terminus of the beta2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues.
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Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel.
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Brenner R
et al.
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Xia XM
et al.
Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells.
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Solaro CR
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Inactivating and noninactivating Ca(2+)- and voltage-dependent K+ current in rat adrenal chromaffin cells.
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