Transglutaminase 4/TGM4: Proteins and Enzymes

The principal activity of transglutaminases (TGMs) is to catalyze the Ca²⁺-dependent formation of an isopeptide bond between the gamma-carboxamide group of a glutaminyl residue and the epsilon-amino group of a lysyl residue. TGMs can also catalyze the attachment of polyamines to the gamma-carboxamide group of a glutaminyl residue and the deamidation of glutaminyl residues. Several TGMs have also been shown to possess protein disulfide isomerase activity. Protein aggregates in the brain are a common feature of a number of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s. Recent reports indicate that TGMs contribute to the formation of protein aggregates in the brain by crosslinking proteins such as Huntingtin and ataxins.

TGM4 is known as the prostate-specific transglutaminase because it is expressed and secreted exclusively by the prostate gland.6 In rodents, TGM4 is required for the formation of the copulatory plug and sperm antigenicity, but its function in humans is not understood. The expression of TGM4 is primarily regulated by retinoic acid and to a lesser degree by androgens.