KCNMB3 is encoded by the KCNMB3 gene which is located on 3q26.3-q27.1 in humans, and the location is closed to KCNMB2. It has been found that the gene encodes more than five isoforms through alternative splicing. The molecular mass of KCNMB3 is about 27 kDa. Different isoforms possess different distributions and even different functions. Three of them are wildly expressed in human tissues, but isoform 2 is mainly expressed in the placenta, pancreas, kidney and heart according to UniProt. Besides, KCNMB3 belongs to the KCNMB (TC 8.A.14.1) family.
|Basic Information of KCNMB3|
|Protein Name||Calcium-activated potassium channel subunit beta-3|
|Aliases||BK channel subunit beta-3, BKbeta3, Hbeta3, Calcium-activated potassium channel, subfamily M subunit beta-3, Charybdotoxin receptor subunit beta-3, K(VCA)beta-3, Maxi K channel subunit beta-3, Slo-beta-3|
|Organism||Homo sapiens (Human)|
|Transmembrane Times||Multi-pass membrane|
KCNMB3 is a regulatory subunit of the calcium-activated potassium channel. It belongs to the same family as the KCNMB1 and KCNMB2. Similar to the two members, KCNMB3 can regulate the calcium sensitivity and gating kinetics of KCNMA1. So KCNMB3 is closely related to KCNMA1 channel diversity. Beyond that, KCNMB3 also takes part in many other biological processes, such as neuronal action potential. Accordingly, KCNMB3 plays an important role in insulin signaling and β-cell function by regulating glucose homeostasis. PIK3CA-KCNMB3 variants are related to insulin resistance, and the relationship can be regulated by polyunsaturated fatty acids. There are four functionally distinct BK-β3 subunits, a-d, because KCNMB3 gene contains four N-terminal alternative exons. Besides, the gene coding KCNMB3 is a positional and functional candidate for idiopathic generalized epilepsy (IGE), and a functional KCNMB3-truncation participates in the epileptogenic effect.
Fig.1 Interactions between structural domains in BK channels. (Lee, 2010)
CNMB3 is related to insulin signaling and β-cell function. And the neighboring genes PIK3CA is also associated with insulin. So, the authors analyze several SNPs of them and find that polyunsaturated fatty acids can regulate the relationship between the two genes.
There are four functionally distinct BK-β3 subunits, in which, β1, β2 and β4 subunits exhibit higher identity between mouse and human. Authors in this article reveal that physiological functions of KCNMB3 β3 maybe different among mammalian species.
KCNMB3 contains four different isoforms, and the variants are associated with idiopathic epilepsy (IE). At the same time, KCNMB3b expressed in neurons may play permissive roles in the neurons with high levels of neuronal activity that is characteristic of epilepsy.
KCNMB3 is a functional candidate gene for idiopathic generalized epilepsy (IGE). In order to explore the mechanism, authors in this article establish a truncating mutation of KCNMB3, at last, they reveal that the truncation confers a common epileptogenic effect preferentially to the ictogenesis of typical absence seizures.
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