TGM3 gene

TGM3, is a protein coding gene located on chromosome 20p13. The encoded gene product, transglutaminase 3, also known as epidermal transglutaminase, is one of the central enzymes responsible for the formation of protein polymers in the epidermis and hair follicle. TGM3 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.

The transaminase 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 (Chermnykh ES et al. 2020).

Furthermore, the enzyme 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.

TGM3 is increasingly expressed in basal cell carcinomas (Smirnov A et al. 2019).

Transglutaminases (TGM) contribute to the formation of rigid, insoluble macromolecular complexes that are essential for the epidermis and hair follicles to fulfill protective and barrier functions against the environment. Transglutaminases cross-link proteins by catalyzing epsilon-gamma-glutamyl-lysine isopeptide bonds (Chermnykh ES et al. 2020). While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent.

Diseases associated with TGM3 include dermatitis herpetiformis. Dermatitis herpetiformis is characterized by IgA antibody populations against transglutaminase 3 (and transglutaminase 2).

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

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.