Tissue transglutaminase


Tissue transglutaminase

Tissue transglutaminase (abbreviated as TG2 or tTG) is an enzyme (EC number|2.3.2.13) of the transglutaminase family. Like other transglutaminases, it crosslinks proteins between an ε-amino group of a lysine residue and a γ-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.Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. "Biochem J" 2002;368:377-96. PMID 12366374.]

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.Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. "Trends Biochem Sci" 2002;27:534-9. PMID 12368090.] Beside its transglutaminase activity, TG2 is proposed to also act as kinase,Mishra S, Murphy LJ. Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 as an insulin-like growth factor-binding protein-3 kinase. "J Biol Chem" 2004;279:23863-8. PMID 15069073.] and protein disulfide isomerase,Hasegawa G, Suwa M, Ichikawa Y, Ohtsuka T, Kumagai S, Kikuchi M, Sato Y, Saito Y. A novel function of tissue-type transglutaminase: protein disulphide isomerase. "Biochem J" 2003; 373:793-803. PMID 12737632.] and deamidase.Sakly W, Thomas V, Quash G and El Alaoui S. A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity. "Clin Exp Immunol" 2006;146:550-8. PMID 17100777.] 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. [Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D. Identification of tissue transglutaminase as the autoantigen of celiac disease. "Nature Med" 1997;3:797-801. PMID 9212111]

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 [Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, Fasano A, Ventura A, Not T. Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease. "Am J Gastroenterol" 2000;95:1253-7. PMID 10811336.]

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.

References

External links

* [http://www.antibodypatterns.com/endomysial.php Endomysial antibodies]
* A collection of substrates and interaction partners of TG2 is accessible in the [http://genomics.dote.hu/wiki/index.php/Main_Page TRANSDAB] , an interactive transglutaminase substrate database.

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