KCNMA1 is encoded by the KCNMA1 gene which is located on 10q22-q23. Up to now, there are 7 isoforms of KCNMA1 which are produced by alternative splicing have been described in Uniprot. And the molecular mass of KCNMA1 is about 137 kDa. It is widely expressed in the membranes of human cells besides myocytes. KCNMA1 belongs to potassium channel family, the members of which make up potassium-selective channels and can be found in virtually all living organisms.
|Basic Information of KCNMA1|
|Protein Name||Calcium-activated potassium channel subunit alpha-1|
|Aliases||BK channel, BKCA alpha, Calcium-activated potassium channel, subfamily M subunit alpha-1, K(VCA)alpha, KCa1.1, Maxi K channel, MaxiK, Slo-alpha, Slo1, Slowpoke homolog, Slo homolog, hSlo|
|Organism||Homo sapiens (Human)|
|Transmembrane Times||Multi-pass membrane|
KCNMA1 is a calcium-activated potassium channel subunit. It owns a diversity of biological functions, such as actin binding, large conductance calcium-activated potassium channel activity, outward rectifier potassium channel activity and so on. It has been reported that KCNMA1 play an important role in negative regulation of cell volume and cellular potassium ion homeostasis. KCNMA1 also takes part in positive regulation of apoptotic process and smooth muscle contraction involved in micturition according to the previous researches. What’s more, the calcium-sensing activity of KCNMA1 can recognize the increase in cytosolic Ca2+ and membrane depolarization. Besides, KCNMA1 is able to respond to ethanol and carbon monoxide-bound heme and then change channel activation, at the same time, it is highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX). The mutations of KCNMA1 is related to paroxysmal nonkinesigenic dyskinesia 3, with or without generalized epilepsy (PNKD3), which is an autosomal dominant neurologic disorder.
Fig.1 Topologies of varied subfamilies of K+ channels, including KCNMA1. (Jiang, 2001)
Authors of this article find that KCNMA1 is an important suppressor in gastric carcinogenesis. Promoter hypermethylation correlates with the tumorgenesis, by a genome-wide methylation detection, they reveal that the hypermethylation is an independent prognostic factor in patients with gastric cancer.
This article suggests that the lncRNA muscleblind-like 1 antisense RNA 1 can negatively regulate the KCNMA1 in the cGMP-PKG signaling pathway. The authors also find that upregulating KCNMA1 expression may influence the apoptosis of skeletal muscle cells.
By whole-cell patch clamp recordings and proliferation assays, the authors in this article confirm the function of KCNMA1 in breast cancer. They reveal that KCNMA1 is strongly expressed in human breast cancer cell line. And its overexpression is related to the high proliferation rate and malignancy of cancer.
In order to determine how KCNMA1 works in osteoblasts, authors in this article knockout the KCNMA1 protein in rat ROS17/2.8 osteoblast. The result suggests that KCNMA1 regulates the proliferation and differentiation of osteoblasts.
This article reveals that Slo1, also named KCNMA1, has a conserved haem-binding sequence motif. Haem is crucial in our body, and it plays a central role in the redox-sensitive reaction. By performing electrophysiological and structural experiments, the authors suggest that haem regulates cloned human Slo1 channels directly.
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