Transglutaminase 1/TGM1: 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.

TGM1, also known as keratinocyte and epidermal transglutaminase, is responsible for the crosslinking of epidermal proteins during the formation of the stratum corneum. Mutations of TGM1 result in a number of skin diseases, notably ichthyosis lamellar type 1.5 TGM1 exists both as a cell surface protein tethered to the plasma membrane through lipid modifications or as a soluble protein that is released from the membrane by proteolysis.