This archaeal enzyme produces the trimethylated product diphthine, which is converted into diphthamide by EC 6.3.1.14, diphthine¡ªammonia ligase. Different from the eukaryotic enzyme, which produces diphthine methyl ester (cf. EC 2.1.1.314). In the archaeon Pyrococcus horikoshii the enzyme acts on His600 of elongation factor 2.