A family of enzymes that catalyze the formation of a covalent bond between the epsilon-amino group of a protein- or peptide-bound lysine and the gamma-carboxyamide group of a protein- or peptide-bound glutamine. These proteins are involved in the crosslinking of proteins in blood coagulation, skin formation and hair development.

Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.