KCNMA1 Membrane Protein Introduction

Introduction of KCNMA1

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
Gene Name KCNMA1
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)
UniProt ID Q12791
Transmembrane Times Multi-pass membrane
Length (aa) 1236

Function of KCNMA1 Membrane Protein

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.

Topologies of varied subfamilies of K+ channels, including KCNMA1. Fig.1 Topologies of varied subfamilies of K+ channels, including KCNMA1. (Jiang, 2001)

Application of KCNMA1 Membrane Protein in Literature

  1. Ma G., et al. KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome. Mol Cancer. 2017, 16(1):46. PubMed ID: 28231797

    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.

  2. Li X.F., et al. Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1. Exp Mol Med. 2018, 50(9): 115. PubMed ID: 30185781

    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.

  3. Oeggerli M., et al. Role of KCNMA1 in Breast Cancer. Plos One. 2012, 7(8): e41664. PubMed ID: 22899999

    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.

  4. Hei H., et al. BK Knockout by TALEN-Mediated Gene Targeting in Osteoblasts: KCNMA1 Determines the Proliferation and Differentiation of Osteoblasts. Mol Cells. 2016, 39(7):530-5. PubMed ID: 27329042

    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.

  5. Tang X.D., et al. Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature. 2003, 425(6957):531-535. PubMed ID: 14523450

    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.

KCNMA1 Preparation Options

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  1. Jiang Y, et al. (2001). Structure of the RCK domain from the E.coli k+ channel and demonstration of its presence in the human bk channel. Neuron. 29(3): 593-601.

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