Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. Dph-1 and dph-2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising dph-3 and a NADH-dependent reductase, predominantly cbr-1 (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the dph-1 subunit (By similarity). Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the reduction of the catalytic iron-sulfur cluster in the dph-1 subunit. Protein modification; peptidyl-diphthamide biosynthesis. Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of dph-1, dph-2, dph-3 and a NADH-dependent reductase, predominantly cbr-1. Belongs to the DPH1/DPH2 family. DPH2 subfamily.