NADH-dependent reductase for DPH3 and cytochrome b5. Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. 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 DPH3 and a NADH-dependent reductase, predominantly CBR1. By reducing DPH3, also involved in the formation of the tRNA wobble base modification mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine), mediated by the elongator complex. The cytochrome b5/NADH cytochrome b5 reductase electron transfer system supports the catalytic activity of several sterol biosynthetic enzymes. 2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + H(+) + NAD(+) 2 Fe(3+)-[Dph3] + NADH = 2 Fe(2+)-[Dph3] + H(+) + NAD(+) Protein modification; peptidyl-diphthamide biosynthesis. Monomer. Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase, predominantly CBR1. Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.