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BKB4

potassium large conductance calcium-activated channel, subfamily M, beta member 4
Synonyms: kcnmb4. Symbol: Kcnmb4

Introductions


Beta-Subunits alter the Ca2+ sensitivity and gating kinetics of MaxiK channels, greatly contributing to MaxiK channel diversity. They also modify the MaxiK channel pharmacological properties, changing toxin binding and acting as receptors for drugs. Thus they allow the MaxiK channel to play important physiological roles. Orio [540]

MaxiK (BK) channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by the gene KCNMB4 is BKB4, an auxiliary beta subunit which slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit.

http://www.ncbi.nlm.nih.gov/gene/27345

Genes


Sequence similarities are major between BKB1-BKB2 and BKB2-BKB3, respectively. BKB4 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]

Kcnmb4 : potassium large conductance calcium-activated channel, subfamily M, beta member 4

RGD ID Chromosome Position Species
620728 7 55751633-55807075 Rat
732910 10 115854924-115910579 Mouse
1343155 12 70760062-70824978 Human

Transcripts


Acc No Sequence Length Source
NM_023960 NCBI
NM_021452 NCBI
NM_014505 NCBI

Ontologies


Accession Name Definition Evidence
GO:0008076 voltage-gated potassium channel complex A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. ISS
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA
GO:0005887 integral to plasma membrane Penetrating at least one phospholipid bilayer of a plasma membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. ISS
GO:0008076 voltage-gated potassium channel complex A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. IEA
GO:0005887 integral to plasma membrane Penetrating at least one phospholipid bilayer of a plasma membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. IEA

Interactions


The BKB4-subunit decreases the CTX binding strength. If the external loops of the BKB1- and BKB4-subunits are exchanged (chimeras b1Lb4 and b4Lb1), the phenotypes obtained regarding toxin binding correspond to their respective loops (e.g., chimera b1Lb4 has a toxin sensitivity corresponding to the BKB4 subunit). These results suggest that the loops of the b-subunits determine the characteristic of toxin binding. (Meera [1190], Orio [540])

BKB4 channels were not blocked by 100 nM charybdotoxin or iberiotoxin, and were activated by 17-beta-estradiol. Behrens [1173]

Proteins


Structures


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 in Orio [540]). The loop has three or four putative glycosylation sites (Orio [540]). At present, four beta-subunits have been cloned in mammals (Meera [1190], Brenner [1181], Knaus (#a1187), Uebele [1179], Xia [1187]). Because CTX is a pore-blocking toxin, it is suggested that the extracellular loop of b-subunits (at least BKB1 and BKB4) faces the pore and is very close to it (Meera [1190]).

Distributions


Expressions


The BKB4-subunit, also cloned from human EST databases, is expressed mainly in brain. Orio [540]

Functionals


Kinetics


Coexpression of BKB4 with the alpha-subunit decreases the apparent Ca2+ sensitivity of the MaxiK channel (Brenner [1181], Meera [1190]). Although this subunit slows down channel activation kinetics in a manner similar to the b1-subunit, the deactivation kinetics is very fast (similar to that observed in absence of the b-subunit; see Fig. 2 in Orio [540] and Brenner [1181]). These results indicate that the functional coupling of this subunit with the alpha-subunit is different from that induced by the other b-subunits.

Models


References


[244 : 12629172]
[1187 : 19578543]
[1188 : 18559348]
[1189 : 12223479]
[540 : 12136044]
[1173 : 10828459]
[1190 : 10792058]
[1181 : 10692449]
[1167 : 8006036]
[1179 : 10766764]

Credits