epidermal transglutaminase

Enzyme formed by keratinocytes that belongs to the transglutaminase family. These are enzymes that catalyze the cross-linking of proteins through epsilon-gamma-glutamyl-lysine isopeptide bonds. Epidermal transglutaminase is encoded by the TGM3 gene, which is located on chromosome 20p13. It initially consists of two polypeptide chains that are activated from a single precursor protein by proteolysis. The activation of the enzyme is controlled by guanosine triphosphate (GTP). Its hydrolysis to GDP leads to the release of the active catalytic domain, which then enables the transglutaminase reaction.

Epidermal transglutaminase is involved in the later stages of cell envelope formation in the epidermis and in the hair follicle. The enzyme catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins as well as the conjugation of polyamines to proteins. It is involved in the formation of the "cornified envelope" (CE), a specialized component consisting of covalent cross-links of proteins under the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-links to form small interchain oligomers, which are further cross-linked by TGM1 on the growing CE scaffold. In hair follicles, it is involved in the cross-linking of structural proteins to harden the inner root sheath.

One of the diseases associated with TGM3 is dermatitis herpetiformis. In dermatitis herpetiformis, mainly IgA autoantibodies against epidermal transglutaminase are detected.

Mutations in the TGM3 gene are detected in uncombable hair syndrome (Basmanav FB et al. 2016).

Epidermal transglutaminase is mainly synthesized in keratinocytes. The synthesis of the protein is regulated by various processes during cell differentiation.

1. Basmanav FB et al. (2016) Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. Am J Hum Genet 99:1292-1304.
2. Chermnykh ES et al. (2020) Transglutaminase 3: The Involvement in Epithelial Differentiation and Cancer. Cells 9:1996.
3. Smirnov A et al. (2019) Transglutaminase 3 is expressed in basal cell carcinoma of the skin. Eur J Dermatol 29: 477-483.