Alpha-kinases present a family of protein kinases that do not have detectable sequence similarity to conventional protein kinases, yet have remarkable structural similarity to the protein kinase fold. The family was initially represented by the Dictyostelium myosin heavy chain kinases and eukaryotic elongation factor 2-kinase (eEF-2 kinase). Analyses of various genome-sequencing projects reveal proteins with an alpha-kinase domain present in protozoans, fungi and all vertebrates. We explore the evolution of the alpha-kinase family, and discuss its consensus motif. This motif falls naturally into eight subdomains, which with two further subdivisions correlate exactly with the first ten subdomains of conventional protein kinases. Consensus motifs and key catalytic residues that are characteristic for conventional protein kinases are highly conserved within the alpha-kinase family. Modeling studies illustrate docking of MHCK A with its coiled-coil substrate, myosin.