TGAs

TGAs, or transglutaminases, are a family of enzymes that catalyze covalent bonds between proteins. They mediate transamidation by forming an isopeptide bond between the gamma-carboxamide group of a glutamine residue and a primary amine (often a lysine), producing gamma-glutamyl-ε-lysine crosslinks and releasing ammonia. Most mammalian TGAs require calcium for activity, and several are regulated by nucleotides such as GTP or GDP.

The best-studied member is tissue transglutaminase (TGM2), widely expressed and found in the cytosol, nucleus, and extracellular matrix. Other family members include TGM1, TGM3, and TGM5 through TGM7, with distinct tissue distributions and substrate preferences. Microbial transglutaminase, produced by bacteria such as Streptomyces, is widely used in industry because it can crosslink proteins at neutral pH and without specific cofactors.

Physiological roles include crosslinking structural proteins in the extracellular matrix and epidermis, stabilizing protein networks during wound healing, and contributing to various cellular processes. In coagulation, related transglutaminases help crosslink fibrin, with Factor XIIIa serving as a coagulation-specific transglutaminase.

Clinical relevance includes associations with fibrotic diseases and autoimmune conditions such as celiac disease, where autoantibodies target TG2. TGAs are also explored in cancer and neurodegeneration research due to their widespread influence on protein networks.

Detection and industry: TG activity can be measured by assays that monitor amine incorporation or gamma-glutamyl-ε-lysine crosslinks. Industrially, transglutaminase is used to improve texture and moisture in meat and dairy products and to bind ingredients in surimi, bakery, and other foods.