Transglutaminase family (TG)

The transglutaminase family comprises eight calcium-dependent enzymes (TG1–TG7 and Factor XIII) that catalyze post-translational modifications, primarily the formation of covalent isopeptide bonds between glutamine and lysine residues [UniProt: P21980]. These enzymes are vital for biological processes such as blood coagulation, skin barrier formation, and extracellular matrix stabilization [StatPearls: Transglutaminase]. TG2, the most widely studied member, is implicated in the pathogenesis of celiac disease as the primary autoantigen and is also linked to fibrosis and cancer progression [PubMed: 33406324]. Factor XIII is crucial for stabilizing fibrin clots, and its deficiency leads to severe bleeding disorders [NIH: GeneReviews]. Therapeutic targeting of transglutaminases, such as the use of the specific inhibitor ZED1227 for celiac disease, aims to block aberrant transamidation or deamidation to prevent tissue damage [ClinicalTrials.gov: NCT03565445]. However, the high structural homology between isozymes poses a significant challenge for developing selective inhibitors that do not disrupt essential physiological functions like hemostasis [Journal of Medicinal Chemistry, 2020].

Other names

Protein-glutamine gamma-glutamyltransferaseTGaseFactor XIIITissue transglutaminaseKeratinocyte transglutaminaseEpidermal transglutaminaseProstate transglutaminaseNeuronal transglutaminase

Inhibition of the transamidation activity that catalyzes the formation of epsilon-(gamma-glutamyl)lysine isopeptide bonds between proteins [UniProt: P21980].