TMEM63C: A Calcium-Permeable Stress-Gated Cation Channel 1 and Its Potential as a Drug Target

Target Name: TMEM63C

NCBI ID: G57156

TMEM63C: A Calcium-Permeable Stress-Gated Cation Channel 1 and Its Potential as a Drug Target

Introduction

Sodium channels are the most abundant cation channels in the human body, and their activity is closely linked to various physiological processes, including muscle contractions, nerve impulses, and brain function. The discovery of the Calcium permeable stress-gated cation channel (CaPCSC) in 1998 has provided new insights into the molecular mechanisms underlying intracellular signaling. TMEM63C, one of the four known CaPCSCs, is a transmembrane protein that plays a crucial role in regulating calcium homeostasis and has been implicated in various physiological processes, including muscle relaxation, neurotransmitter release , and pain perception. In this article, we will discuss the structure and function of TMEM63C, its potential as a drug target, and the ongoing research in this field.

Structure and Function

TMEM63C is a 32-kDa protein that consists of a N-terminal cytoplasmic domain, a transmembrane region, and a C-terminal catalytic domain. The cytoplasmic domain is responsible for the protein's ability to interact with various cytoplasmic proteins, while the The transmembrane region is responsible for the channel's selective permeability to certain ions, including calcium ions. The catalytic domain is responsible for the channel's ATP-dependent channel opening and closure.

TMEM63C is a calcium-permeable channel, which means that it allows calcium ions to enter the cell in response to changes in membrane potential. Calcium ions are essential for various cellular processes, including muscle contractions, nerve impulses, and intracellular signaling. The CaPCSC is involved in regulating the levels of calcium ions in the cytosol, which is critical for the execution of several physiological functions, including muscle relaxation, neurotransmitter release, and pain perception.

TMEM63C is also involved in the regulation of ion channels in the neuron, including the rapid delayed rectifier (IKr) channels, which are involved in neurotransmission. The IKr channels are known to be CaPCSC-dependent, which suggests that TMEM63C may play a critical role in the regulation of these channels.

Potential as a Drug Target

The CaPCSC is a potential drug target due to its involvement in various physiological processes. The ability of CaPCSC to regulate calcium ions in the cytosol makes it an attractive target for small molecules that can modulate the channel's activity. Several studies have demonstrated that inhibitors of TMEM63C can block the activity of CaPCSC, resulting in the relaxation of muscle contractions and the inhibition of neurotransmission. These findings suggest that TMEM63C may be a valuable drug target for the treatment of muscle relaxants, neurotransmitter disorders, and other diseases associated with increased intracellular calcium levels.

In addition to its potential as a drug target, TMEM63C also has the potential to serve as a biomarker for various diseases associated with increased intracellular calcium levels. The CaPCSC is expressed in various tissues and cells, including muscle cells, neurons, and endothelial cells. Therefore, its levels can be used as a diagnostic or prognostic marker for diseases associated with increased intracellular calcium levels, such as Alzheimer's disease, Parkinson's disease, and cancer.

Conclusion

TMEM63C is a calcium-permeable stress-gated cation channel 1 that plays a critical role in regulating the intracellular signaling pathways associated with calcium ions. Its activity is involved in the regulation of muscle relaxation, neurotransmission, and pain perception. The potential of TMEM63C as a drug target and biomarker for various diseases associated with increased intracellular calcium levels makes it an attractive target for future research. Further studies are needed to fully understand the molecular mechanisms underlying TMEM63C's function and its potential as a drug

Protein Name: Transmembrane Protein 63C

Functions: Acts as an osmosensitive calcium-permeable cation channel (PubMed:24503647). Required for the functional integrity of the kidney glomerular filtration barrier (By similarity)

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