KCNMB4 Membrane Protein Introduction

Introduction of KCNMB4

KCNMB4 is encoded by the KCNMB4 gene which is located on 12q15. The molecular mass of KCNMB4 is about 23 kDa. It belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4 is mainly expressed in the brain, weakly or not expressed in other tissues. Post-translational modifications reported in KCNMB4 mainly include phosphorylation and glycosylation, and both are associated with biological functions of KCNMB4.

Function of KCNMB4 Membrane Protein

KCNMB4 is one of the regulatory subunits of the calcium-activated potassium channel. It belongs to the same family as KCNMB1, KCNMB2 and KCNMB3. Just like the three members, KCNMB4 can decrease the calcium sensitivity and gating kinetics of KCNMA1. So KCNMB4 is closely related to KCNMA1 channel diversity. Beyond that, KCNMB4 also takes part in many other biological processes, such as action potential, regulation of neurotransmitter secretion and chemical synaptic transmission. Accordingly, the phosphorylation state of KCNMB4 in human is crucial for the functional relationship between KCNMB4 and KCNMA1. Thr-11, Ser-17 and Ser-210 are the potential phosphor-epitopes of KCNMB4 and phosphorylation of different residues can result in different influence. At the same time, KCNMB4 can help KCNMB3 to resistant to charybdotoxin (CTX) toxin, and the resistance is mediated by the extracellular domain of KCNMB4. Besides, a seizure will induce downregulation of KCNMB4, which increases the excitability of dentate gyrus neurons.

Fig.1 Calcium-activated potassium channel structure. (Lee, 2010)

Application of KCNMB4 Membrane Protein in Literature

1. Whitmire L.E., et al. Downregulation of KCNMB4 expression and changes in BK channel subtype in hippocampal granule neurons following seizure activity. Plos One. 2017, 12(11): e0188064. PubMed ID: 29145442
   
   

   It has been found that BK channels are important for early spike timing in neurons, and they contribute to the increase of excitability in the early stage of seizure. Authors in this article reveal that seizure induces the downregulation of KCNMB4 which increases the excitability of dentate gyrus neurons.

2. Manna I., et al. Failure to confirm association of a polymorphism in KCNMB4 gene with mesial temporal lobe epilepsy. Epilepsy Research. 2013, 106(1-2):284-287. PubMed ID: 23623847
   
   

   It has been reported that a tagging single nucleotide polymorphism (SNP) located on the 3'-end of KCNMB4 maybe a susceptibility allele for mesial temporal lobe epilepsy (mTLE). In order to confirm the finding, a cohort of 332 patients are examined, and the result reveals that the SNP can not influence significantly the risk of developing mTLE or its severity.

3. Meera P., et al. A neuronal β subunit (KCNMB4) makes the large conductance, voltage^- and Ca²⁺-activated K⁺ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci U S A. 2000, 97(10):5562-5567. PubMed ID: 10792058
   
   

   The pore blockers charybdotoxin (CTx) and iberiotoxin (IbTx) can influence the physiological function of BK channel invertebrates. Authors in this article find that KCNMB4 can make KCNMA1 resistant to nanomolar concentrations of CTx and IbTx.

4. Yang J., et al. Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma. J Hematol Oncol. 2014, 7:76. PubMed ID: 16958040
   
   

   Authors in this article perform transcriptome sequencing to characterize the gene fusions in 11 human osteosarcomas. It is the first time to develop a whole transcriptome analysis of untreated human osteosarcoma. They reveal that KCNMB4-CCND3 fusion genes contribute to tumor cell motility in human osteosarcoma.

5. Jin P., et al. Phosphorylation-dependent Functional Coupling of hSlo Calcium-dependent Potassium Channel and Its hβ4 Subunit. Journal of Biological Chemistry. 2002, 277(12): 10014. PubMed ID: 11790768
   
   

   Post-translation modifications play important roles in the function of proteins, and this article reports three putative phosphorylation sites in KCNMB4. And authors reveal that phosphorylation is crucial for the functional relationship between KCNMB4 and KCNMA1.

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Reference

1. Lee U S and Cui J. (2010). Bk channel activation: structural and functional insights. Trends in Neurosciences. 33(9): 0-423.

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