Protein-glutamine gamma-glutamyltransferase E (TGM3)

Protein-glutamine gamma-glutamyltransferase E (TGM3) is a calcium-dependent enzyme belonging to the transglutaminase family. It catalyzes the cross-linking of structural proteins in the skin and hair by forming isopeptide bonds between glutamine and lysine residues, a process critical for epidermal cornification and hair shaft formation[1][2][3][4][5]. TGM3 exists as an inactive precursor that undergoes proteolytic cleavage to yield active chains, functioning predominantly in upper epidermal layers and all compartments of the hair follicle. TGM3 plays a major role in maintaining the barrier function of stratified epithelial tissues, and its deficiency or dysfunction results in disorders such as uncombable hair syndrome and contributes to cancer pathogenesis[1][2][3][4]. TGM3 is also a key autoantigen in gluten-related disorders like dermatitis herpetiformis, making it clinically relevant as both a therapeutic target and biomarker[2][4].

Other names

Transglutaminase 3Epidermal transglutaminaseTGase-3TGase ETGEE polypeptideProtein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chainProtein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chainUHS2

For hypothetical drugs, the mechanism of action would involve inhibition of transglutaminase activity, modulation of cross-linking enzymatic function, or immunomodulation (modifying antibody interactions). In the context of autoantibodies, they bind TGM3 in dermatitis herpetiformis and disrupt its physiological role.