Transient receptor potential cation channel subfamily M member 7 (TRPM7) kinase domain (TRPM7 kinase)

Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a unique chanzyme that combines a non-selective cation channel with a C-terminal serine/threonine-protein kinase domain (UniProt Q96QT4). It plays a critical role in maintaining cellular magnesium and calcium homeostasis, which is essential for various physiological processes including cell proliferation, migration, and survival (PubMed: 11331883). The kinase domain of TRPM7 regulates the channel's activity and phosphorylates several downstream substrates, such as annexin A1 and myosin II heavy chain, thereby influencing the cytoskeleton and signal transduction (PubMed: 22334664). In pathological contexts, TRPM7 is frequently overexpressed in various cancers, where it promotes tumor growth and metastasis, and it is also implicated in neuronal death following ischemic stroke (PubMed: 24561240). Pharmacological targeting of the TRPM7 kinase domain or its channel activity is being explored as a potential therapeutic strategy for oncology and neurological disorders (PubMed: 30104340). However, the ubiquitous expression of TRPM7 and its fundamental role in ion balance present significant challenges for drug development and safety (PubMed: 28811357).

Other names

TRP-PLIKChaK1LTRPC7ChanzymeTRPM7 kinase

Inhibition of the C-terminal serine/threonine kinase activity or blockade of the associated ion channel pore to modulate magnesium influx and downstream signaling pathways.