Kinase Subfamily ChaK
Kinase Classification: Group PKL: Family Alpha: Subfamily ChaK
A vertebrate-specific fusion between a TRMP cation channel and an alpha kinase.
Domain Structure
Members have a 6-transmembrane-region TRPM channel followed by an alpha kinase domain.
Evolution
Vertebrates have two ChaKs: ChaK1 (TRPM7) and ChaK2 (TRPM6). The channel portion of Chak has two other vertebrate orthologs (TRPM1, TRPM3), and typically a single invertebrate ortholog (e.g. Drosophila CG30078), suggesting that Chaks are the result of a gene fusion followed by duplication. The alpha kinase domain appears to have a homolog in the chordate Saccoglossus, but no associated channel could be found in EST database or gene predictions.
Functions
Crystal structure of the CHAK1 gene [1] shows a PKL fold, and catalytic activity has been demonstrated for many members of this family. The channels are Mg and Ca-selective and well studied functionally, but the role of the kinase domain is not well understood. TRPM6 may act as an Mg sensor, and regulate the channel; it has also been suggested that in TRPM7, it is Ca flux through the channel that regulates kinase activity.
