- Tissue transglutaminase
Tissue transglutaminase (abbreviated as TG2 or tTG) is an
enzyme (EC number|2.3.2.13) of thetransglutaminase family. Like other transglutaminases, it crosslinksprotein s between an ε-amino group of a lysine residue and a γ-carboxamide group ofglutamine residue, creating an inter- or intramolecular bond that is highly resistant toproteolysis (protein degradation). It is particularly notable for being the autoantigen incoeliac disease , but is also known to play a role inapoptosis ,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 inwound healing ,apoptosis andextracellular matrix developmentTG2 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 ofcoeliac disease .Role in disease
Tissue transglutaminase is best known for its link with
coeliac disease .Anti-transglutaminase antibodies (ATA) result in a form ofgluten sensitivity in which a cellular response to "Triticeae" glutens that are crosslinked to tTG are able to stimulate transglutaminase specificB-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.PBB_Controls
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