Diphthamide biosynthesis protein 3 (DPH3)

Diphthamide biosynthesis protein 3 (DPH3) is a small, CSL-type zinc finger-containing protein essential for the post-translational modification of elongation factor 2 (eEF2) at a specific histidine residue, resulting in the diphthamide group—this modification is the target for ADP-ribosylation by bacterial toxins such as diphtheria toxin and Pseudomonas exotoxin A, which inactivates eEF2 and halts protein synthesis. DPH3 acts as an electron donor, transferring electrons to and helping maintain the [4Fe–4S] clusters in the DPH1–DPH2 enzyme complex, enabling the critical first step of diphthamide biosynthesis. DPH3 also participates in tRNA modifications via interaction with the elongator complex, and may play broader roles in cellular processes including transcription regulation and endocytosis, though these are less well characterized. DPH3 is not itself considered a direct therapeutic target, but its function is crucial for the sensitivity of cells to certain bacterial toxins.

Other names

DESR1ZCSL2DelGIP1DELGIP1MGC20197KTI11DELGIPDPH3ACSL-type zinc finger-containing protein 2DelGEF-interacting protein 1KTI11 homolog A (S. cerevisiae)DPH3 homolog (KTI11, S. cerevisiae)KTI11 homologDel-GEF interacting proteindeafness locus putative guanine nucleotide exchange factor interacting protein 1diphtheria toxin and Pseudomonas exotoxin A sensitivity required gene 1zinc finger, CSL domain containing 2

Not applicable (DPH3 itself is not targeted by therapeutics; rather, its function is essential for post-translational modification of elongation factor 2, which is the target for diphtheria toxin and Pseudomonas exotoxin A)