Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:8406038, PubMed:24422557, PubMed:27694803, PubMed:31463593, PubMed:32576952, PubMed:34154323). DPH1 and DPH2 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 KTI11/DPH3 and a NADH-dependent reductase, predominantly CBR1 (PubMed:8406038, PubMed:24422557, PubMed:27694803, PubMed:31463593, PubMed:34154323). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (PubMed:31463593). Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the reduction of the catalytic iron-sulfur cluster in the DPH1 subunit. Protein modification; peptidyl-diphthamide biosynthesis. Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, KTI11/DPH3 and a NADH-dependent reductase, predominantly CBR1 (PubMed:31463593, PubMed:24422557, PubMed:18627462). Interacts with DPH1; the interaction is direct (PubMed:15485916, PubMed:23645155, PubMed:31463593). Interacts with KTI11/DPH3 (PubMed:12940988, PubMed:27694803, PubMed:18627462). Abolishes diphthamide modification of elongation factor 2 (PubMed:32576952). Abolishes the interaction between DPH1 and DPH3 (PubMed:18627462). Resistance to diphtheria toxin, sordarin, and zymocin (PubMed:18627462, PubMed:27694803, PubMed:32576952). Sensitive to hygromycin B (PubMed:32576952). Present with 3486 molecules/cell in log phase SD medium. Belongs to the DPH1/DPH2 family. DPH2 subfamily.