Alpha

Alpha-kinases are a family of atypical Ser/Thr kinases whose catalytic domains bear no resemblance to the canonical eukaryotic protein kinase fold, placing them in their own evolutionary lineage. The best-studied members are TRPM6 and TRPM7, which fuse an alpha-kinase domain to a divalent-cation channel and regulate magnesium homeostasis, and elongation factor-2 kinase (eEF2K), which throttles translation elongation by phosphorylating eEF2 in response to nutrient and energy status downstream of AMPK and mTOR. Alpha-kinases prefer acidic substrate regions and are regulated by divalent cations and calmodulin rather than by the second messengers that govern AGC or PKC enzymes. Their unique architecture makes them attractive for selective drug design, and recombinant alpha-kinase domains are used in translation-control and ion-channel research.