ChaK1: is an unusual and ubiquitous bifunctional protein containing a transient receptor potential (TRP) ion channel fused to a protein kinase of the Atypical alpha group. Required for early embryonic development and for maintaining cardiac automaticity. The channel conducts Zn(2+), Mg(2+), and Ca(2+) as well as monovalent cations. The kinase can be cleaved from the channel domain. The cleaved kinase translocates to the nucleus where it binds chromatin-remodeling complexes including Polycomb, and phosphorylates specific histone residues. The kinase activity is essential for the channel function, and channel function is critical to maintain physiological intracellular magnesium levels. Plays a key role in oxidative stress-induced cell death. TRP voltage-independent calcium-permeable cation channels are divided into six subfamilies, two of which (TRPC and TRPM) have members that are widely expressed and activated by oxidative stress. Is activated by reactive oxygen/nitrogen species, resulting in cation conductance and anoxic neuronal cell death. This phenotype is rescued by suppression of ChaK1 expression. Related to ChaK2, another Atypical alpha kinase fused to a TRP ion channel protein.
Protein type: Membrane protein, multi-pass; Protein kinase, atypical; Channel, cation; Kinase, protein; Membrane protein, integral; EC 2.7.11.1; ATYPICAL group; Alpha family; ChaK subfamily
Chromosomal Location of Human Ortholog: 15q21
Cellular Component: ruffle; plasma membrane; integral to membrane
Molecular Function: protein serine/threonine kinase activity; myosin binding; metal ion binding; calcium channel activity; actin binding; ATP binding
Biological Process: protein amino acid autophosphorylation; actomyosin structure organization and biogenesis; calcium-dependent cell-matrix adhesion; transmembrane transport
Disease: Amyotrophic Lateral Sclerosis-parkinsonism/dementia Complex 1
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