Diphthamide

Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2).

It is usually found at position H715 in mammalian eEF2 (H699 in yeast). This residue is modified by the protein encoded by the DPH1 (OVCA1) gene. Dph1 knockout mice are inviable while heterozygotes develop diverse types of carcinomas and sarcomas. In humans, DH1 is frequently found mutated in ovarian cancer. Loss of heterozygosity has taken place in 50% of benign tumours, and 90% of end-stage ovarian tumours.