Diphthamide is a modified histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 found in eukaryotic elongation factor 2

Eukaryotic elongation factors

Eukaryotic elongation factors are very similar to those in prokaryotes.Elongation in eukaryotes is carried out with two elongation factors: eEF-1 and eEF-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 OVCA1 gene (homolog of DPH1

DPH1

Diphthamide biosynthesis protein 1 is a protein that in humans is encoded by the DPH1 gene. It encodes a protein that modifies histidine-699 on eukaryotic translation elongation factor 2 to diphthamide. This modification appears to be important in the translation of Cyclin D in ovarian cells...

 in mice). DPH1 knockout mice are inviable while heterozygotes develop diverse types of carcinoma

Carcinoma

Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

s and sarcoma

Sarcoma

A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

s. In humans, OVCA1 is frequently found mutated in ovarian cancer

Ovarian cancer

Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....

. Loss of heterozygosity

Loss of heterozygosity

Loss of heterozygosity in a cell is the loss of normal function of one allele of a gene in which the other allele was already inactivated. This term is mostly used in the context of oncogenesis; after an inactivating mutation in one allele of a tumor suppressor gene occurs in the parent's germline...

 has taken place in 50% of benign tumours, and 90% of end-stage ovarian tumours.

It is ADP-ribosylated by diphtheria toxin

Diphtheria toxin

Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae, the pathogen bacterium that causes diphtheria. Unusually, the toxin gene is encoded by a bacteriophage...

, hence the name, which renders the elongation factor inactive.