diphthine synthase activity https://github.com/geneontology/go-ontology/issues/25281 https://github.com/geneontology/go-ontology/issues/25795 https://github.com/geneontology/go-ontology/issues/30193 Catalysis of the reaction: 2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation elongation factor 2] + 3 S-adenosyl-L-methionine = diphthine-[translation elongation factor 2] + 3 H+ + 3 S-adenosyl-L-homocysteine. This activity is present in archae and produces the trimethylated product diphthine, which is converted into diphthamide by diphthine-ammonia ligase activity ; GO:0017178 (EC:6.3.1.14). Note that this is different from the eukaryotic enzyme diphthine methyl ester synthase activity ; GO:0141133 (EC:2.1.1.314), which produces diphthine methyl ester. diphthine methyltransferase activity S-adenosyl-L-methionine:2-(3-carboxy-3-aminopropyl)-L-histidine methyltransferase activity GO:0004164 EC:2.1.1.98 MetaCyc:RXN-14326 molecular_function RHEA:36415 S-adenosyl-L-methionine:elongation factor 2 methyltransferase activity protein methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity