Transglutaminases (TGMs) represent a family of enzymes capable of stabilizing protein assemblies by gamma-glutamyl-epsilon-lysine crosslinks. TGMs are defined as enzymes capable of forming isopeptide bonds by transfer of an amine onto glutaminyl residues of a protein.

Function

 In the skin, during terminal differentiation, mammalian epidermal cells acquire a deposit of protein 10 to 20 nm thick on the intracellular surface of the plasma membrane, which is termed the cornified or cross-linked cell envelope (CE).

The CE is the most insoluble component of the epidermis due to crosslinking by disulfide bonds as well as by gamma-glutamyl-lysine isodipeptide bonds that are formed by the action of transglutaminases.

Three different glutaminase activities have been identified in mammalian epidermis and other stratified squamous epithelial tissues.

These include TGM2, a ubiquitous type II enzyme formerly called transglutaminase C (MIM.190196); TGM1, a keratinocyte type I activity formerly called transglutaminase K, which is present in cultured epidermal keratinocytes; and TGM3, a so-called epidermal activity, formerly called transglutaminase E (MIM.600238), which is present in hair follicles and advanced differentiated epidermal cells. Transglutaminase K is membrane-associated, whereas the C and E forms are soluble.

Members

Transglutaminases catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds.

The transglutaminases include:

 factor XIII (plasma transglutaminase) (MIM.134570)
 keratinocyte transglutaminase (TGM1) (MIM.190195)
 tissue transglutaminase (TGM2)
 hair follicle transglutaminase (TGM3)
 prostate transglutaminase (TGM4) (MIM.600585)

Although the overall primary structures of these enzymes are different, they all share a common amino acid sequence at the active site (YGQCW) and a strict calcium dependence for their activity. Differences in the primary structures of transglutaminases are probably responsible for their diverse biologic functions. The unique C terminus of TGM2, which is not involved in TGase activity, functions as a G protein in receptor signaling.

Pathology

 germline mutations

 autoantibbody target

See also

 proteic crosslinking