tTG3

Tissue transglutaminase 3 (tTG3) is an enzyme in the transglutaminase family that catalyzes calcium-dependent cross-linking of proteins, forming epsilon-(gamma-glutamyl) lysine isopeptide bonds. Through this activity, it contributes to the stabilization of structural proteins during the process of cornification, which strengthens the epidermal barrier.

tTG3 is encoded by the TGM3 gene. In humans it is expressed predominantly in stratified squamous epithelia, with high levels in the epidermis and hair follicles. In these tissues it participates in forming the cornified cell envelope and supports keratinocyte differentiation, helping to maintain the integrity of the epithelial barrier.

Clinical significance is greatest in dermatitis herpetiformis (DH). In DH, IgA antibodies against TG3 are commonly detected, and TG3 may be present in dermal deposits; anti-TG3 antibodies can aid diagnosis alongside skin biopsy findings. The autoimmune response to TG3 is typically discussed in the context of gluten-sensitive conditions, with TG2 antibodies also appearing in many patients, though TG3 antibodies can be more specific for DH.

Genetics and related notes: The TG3 enzyme is encoded by the TGM3 gene. Rare variants or mutations in TGM3 have been described in some hereditary skin disorders, but most cases of DH and related gluten-associated diseases are not attributed to TGM3 mutations. TG3 is one member of the broader transglutaminase family, which includes TG1 and TG2, and it has distinct tissue distribution and substrate preferences.

See also: transglutaminase family; dermatitis herpetiformis; celiac disease.