Diphthine--ammonia ligase (DPH6)

Diphthine--ammonia ligase (DPH6) is an enzyme that catalyzes the last (amidation) step in the biosynthesis of diphthamide, a unique post-translationally modified histidine residue found in eukaryotic translation elongation factor 2 (eEF2)[2][3][5][7]. DPH6 uses ammonium and ATP to convert diphthine to diphthamide, a modification essential for normal translation and for the sensitivity of eEF2 to diphtheria toxin[1][6][7]. Loss of DPH6 function blocks diphthamide synthesis, causes accumulation of diphthine-modified eEF2, and can result in diphthamide deficiency syndromes[3]. The DPH6 protein is conserved in eukaryotes, contains an ATP-binding domain, and operates as part of the broader diphthamide biosynthesis pathway, which is critical for normal protein synthesis and cell viability[1][3][5][7].

Other names

DPH6diphthamine biosynthesis 6ATPBD4ATP-binding domain-containing protein 4diphthamide synthasediphthamide synthetaseprotein DPH6 homologdiphthine-ammonia ligaseDKFZp313L08395730421E18RikRGD1310006