Tissue transglutaminase

Tissue transglutaminase (abbreviated as TG2 or tTG) is an enzyme of the transglutaminase family. Like other transglutaminases, it crosslinks proteins between an &epsilon;-amino grop of a lysine residue and a &gamma;-carboxamide group of glutamine residue, creating an inter- or intramolecular bond that is highly resistant to proteolysis (protein degradation). It is particularly notable for being the autoantigen in coeliac disease, but is also known to play a role in apoptosis, cellular differentiation and matrix stabilisation.

Genetics
The human tTG gene is located on the 20th chromosome (20q11.2-q12).

Physiology
tTG is expressed ubiquitously. It requires calcium as a cofactor for transamidation activity. Transcription is increased by retinoic acid. Amongst its many supposed functions, it appears to play a role in wound healing, apoptosis and extracellular matrix development

TG2 also has GTPase activity: in the presence of GTP it suggested to function as a G protein participating in signaling processes. Beside its transglutaminase activity, TG2 is proposed to also act as kinase, and protein disulphide isomerase, and deamidase. This latter activity is important in the deamidation of gliadin peptides thus playing important role in the pathology of coeliac disease.

Role in disease
Tissue transglutaminase is best known for its link with coeliac disease. Anti-transglutaminase antibodies (ATA) result in a form of gluten sensitivity in which a cellular response to Triticeae glutens that are crosslinked to tTG are able to stimulate transglutaminase specific B-cell responses that eventually result in the production of ATA IgA and IgG.

Recent studies suggest that tTG plays a role in inflammation, degenerative diseases and tumor biology.

Diagnostic use
Serology for anti-tTG antibodies has superseded older serological tests (anti-endomysium, anti-gliadin and anti-reticulin) and has a strong sensitivity (99%) and specificity (>90%) for identifying coeliac disease. Modern anti-tTG assays rely on a human recombinant protein as an antigen

Therapeutic use
Use of tTG as a form of surgical glue is still experimental. It is also being studied as an attenuator of metastasis in certain tumors.