Alpha-kinases present a family of protein kinases that do not have detectable sequence similarity to conventional protein kinases. The family was initially represented by the Dictyostelium myosin heavy chain kinases and eukaryotic elongation factor 2-kinase (eEF-2 kinase). Five other human proteins with an alpha-kinase catalytic domain are now known. The X-ray structure of the alpha-kinase domain of one of these proteins was recently determined, and significant structural similarity to conventional protein kinases was found [Yamaguchi, 2001 #56]. Orthologs and paralogs to these genes are found in several other vertebrate genomes. Analyses of various genome-sequencing projects reveal several more proteins with an alpha-kinase domain present in Dictyostelium, Entamoeba, Trypanosoma and Neurospora. 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.