BKβ3
Description: potassium large conductance calcium-activated channel, subfamily M beta member 3 Gene: Kcnmb3 Alias: kcnmb3, BKB3
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])
KCNMB3 (also known as HBETA3; KCNMB2; KCNMBL; BKBETA3; SLOBETA3) encodes BKB3, potassium large conductance calcium-activated channel (subfamily M) beta member 3. 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. BKB3 may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22.
http://www.ncbi.nlm.nih.gov/gene/27094
The b3-subunit (BKB3) was cloned from human EST databases and is phylogenetically more related to b2 than to b1 (Uebele [1179]). There are four splice variants (BKB3a-d), whose differences are in the NH2-terminal region. (Orio [540])
The mouse beta3 subunit, excluding N-terminal splice variants, shares only 62.8% amino acid identity with its human counterpart. (Zheng [1184])
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_171828.3 | 1307 | |
Mouse | NM_001195074.1 | 720 | |
Rat | NM_001104560.2 | 1637 |
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 terminals 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]).
BKB3 is phylogenetically more related to BKB2 than to BKB1 (Uebele [1179]). There are four splice variants (BKB3a-d), whose differences are in the NH2-terminal region. (Orio [540])
BKβ3 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
BKB3 was detected in testis, pancreas and spleen (Xia [1182]).
There are four splice variants (BKB3a-d), whose differences are in the NH2-terminal region. Each splice variant confers different inactivation properties to the MaxiK channel. Whereas the BKB3a and BKB3c subunits confer similar inactivation properties, BKB3b induces a faster and incomplete inactivation process that becomes evi- dent only at large depolarizations (Xia [1182]). It is unclear whether or not the BKB3d-subunit interacts with the alpha-subunit since coexpression of alpha- and BKB3d-subunits does not produce changes in the Ca2+ activation curves or in the gating kinetics of the MaxiK channel. (Orio [540])
The BKB3b auxiliary subunit, when coexpressed with the Slo alpha subunit, results in a particularly rapid (1ms), but incomplete inactivation, mediated by the cytosolic NH2 terminus of the BKB3b subunit (Xia et al., 2000 [1182]). See Lingle [1186] for by a two-step blocking mechanism of this process.
References
Orio P
et al.
New disguises for an old channel: MaxiK channel beta-subunits.
News Physiol. Sci.,
2002
Aug
, 17 (156-61).
Knaus HG
et al.
Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle.
J. Biol. Chem.,
1994
Jun
24
, 269 (17274-8).
Uebele VN
et al.
Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel.
J. Biol. Chem.,
2000
Jul
28
, 275 (23211-8).
Brenner R
et al.
Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.
J. Biol. Chem.,
2000
Mar
3
, 275 (6453-61).
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.
J. Neurosci.,
1999
Jul
1
, 19 (5255-64).
Zeng X
et al.
Species-specific Differences among KCNMB3 BK beta3 auxiliary subunits: some beta3 N-terminal variants may be primate-specific subunits.
J. Gen. Physiol.,
2008
Jul
, 132 (115-29).
Hu S
et al.
Variants of the KCNMB3 regulatory subunit of maxi BK channels affect channel inactivation.
Physiol. Genomics,
2003
Nov
11
, 15 (191-8).
Lingle CJ
et al.
Inactivation of BK channels mediated by the NH(2) terminus of the beta3b auxiliary subunit involves a two-step mechanism: possible separation of binding and blockade.
J. Gen. Physiol.,
2001
Jun
, 117 (583-606).
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