KCNMB2 explained

Symbol:	KcnmB2_inactiv
KCNMB2, ball and chain domain
Pfam:	PF09303
Interpro:	IPR015382

Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.^{[1] [2]}

Big Potassium (BK) channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. BK channels can contain two distinct subunits: a pore-forming alpha subunit and a modulatory beta subunit. Each complete BK channel contains four copies of the pore-forming alpha subunit and up to four beta subunits. The protein encoded by the KCNMB2 gene is an auxiliary beta subunit which influences the calcium sensitivity of BK currents and, following activation of BK current, causes persistent inactivation. The subunit encoded by the KCNMB2 gene is expressed in various endocrine cells, including pancreas and adrenal chromaffin cells. It is also found in the brain, including the hippocampus. The KCNMB2 gene is homologous to three other genes found in mammalian genomes: KCNMB1 (found primarily in smooth muscle), KCNMB3, and KCNMB4 (the primary brain BK auxiliary subunit).

Calcium-activated potassium channel subunit beta-2 comprises two domains. An N-terminal cytoplasmic domain, the ball and chain domain, which is responsible for the fast inactivation of these channels,^[3] and a C-terminal calcium-activated potassium channel beta subunit domain. The N-terminal domain only occurs in calcium-activated potassium channel subunit beta-2, while the C-terminal domain is found in related proteins.

See also

• BK channel
• Voltage-gated potassium channel

Further reading

• Orio P, Rojas P, Ferreira G, Latorre R . New disguises for an old channel: MaxiK channel beta-subunits . News Physiol. Sci. . 17 . 4. 156–61 . 2002 . 12136044 . 10.1152/nips.01387.2002. 10533/173696 . free .
• Xia XM, Ding JP, Lingle CJ . Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells . J. Neurosci. . 19 . 13 . 5255–64 . 1999 . 10377337 . 10.1523/JNEUROSCI.19-13-05255.1999. 6782330 .
• Brenner R, Jegla TJ, Wickenden A, etal . Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4 . J. Biol. Chem. . 275 . 9 . 6453–61 . 2000 . 10692449 . 10.1074/jbc.275.9.6453 . free .
• Liu QH, Williams DA, McManus C, etal . HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation . Proc. Natl. Acad. Sci. U.S.A. . 97 . 9 . 4832–7 . 2000 . 10758170 . 10.1073/pnas.090521697 . 18318 . 2000PNAS...97.4832L . free .
• Uebele VN, Lagrutta A, Wade T, etal . Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel . J. Biol. Chem. . 275 . 30 . 23211–8 . 2000 . 10766764 . 10.1074/jbc.M910187199 . free .
• Meera P, Wallner M, Toro L . A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin . Proc. Natl. Acad. Sci. U.S.A. . 97 . 10 . 5562–7 . 2000 . 10792058 . 10.1073/pnas.100118597 . 25868 . 2000PNAS...97.5562M . free .
• Bentrop D, Beyermann M, Wissmann R, Fakler B . NMR structure of the "ball-and-chain" domain of KCNMB2, the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels . J. Biol. Chem. . 276 . 45 . 42116–21 . 2001 . 11517232 . 10.1074/jbc.M107118200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Xia XM, Ding JP, Lingle CJ . 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 . J. Gen. Physiol. . 121 . 2 . 125–48 . 2003 . 12566540 . 10.1085/jgp.20028667 . 2217327 .
• Hartness ME, Brazier SP, Peers C, etal . Post-transcriptional control of human maxiK potassium channel activity and acute oxygen sensitivity by chronic hypoxia . J. Biol. Chem. . 278 . 51 . 51422–32 . 2004 . 14522958 . 10.1074/jbc.M309463200 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Orio P, Torres Y, Rojas P, etal . Structural determinants for functional coupling between the beta and alpha subunits in the Ca2+-activated K+ (BK) channel . J. Gen. Physiol. . 127 . 2 . 191–204 . 2006 . 16446507 . 10.1085/jgp.200509370 . 2151488 .
• Zeng XH, Benzinger GR, Xia XM, Lingle CJ . BK channels with beta3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism . J. Neurosci. . 27 . 17 . 4707–15 . 2007 . 17460083 . 10.1523/JNEUROSCI.0758-07.2007 . 6672991 . free .
• Zarei MM, Song M, Wilson RJ, etal . Endocytic trafficking signals in KCNMB2 regulate surface expression of a large conductance voltage and Ca(2+)-activated K+ channel . Neuroscience . 147 . 1 . 80–9 . 2007 . 17521822 . 10.1016/j.neuroscience.2007.04.019 . 24449192 .

Notes and References

1. Wallner M, Meera P, Toro L . Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog . Proc Natl Acad Sci U S A . 96 . 7 . 4137–42 . May 1999 . 10097176 . 22433 . 10.1073/pnas.96.7.4137 . 1999PNAS...96.4137W . free .
2. Web site: Entrez Gene: KCNMB2 potassium large conductance calcium-activated channel, subfamily M, beta member 2.
3. Bentrop D, Beyermann M, Wissmann R, Fakler B . NMR structure of the "ball-and-chain" domain of KCNMB2, the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels . J. Biol. Chem. . 276 . 45 . 42116–21 . November 2001 . 11517232 . 10.1074/jbc.M107118200 . free .