- Tissue transglutaminase
Tissue transglutaminase (abbreviated as TG2 or tTG) is an
enzyme(EC number|188.8.131.52) of the transglutaminasefamily. Like other transglutaminases, it crosslinks proteins between an ε- aminogroup of a lysine residue and a γ-carboxamide group of glutamineresidue, 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 differentiationand matrix stabilisation.Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. "Biochem J" 2002;368:377-96. PMID 12366374.]
The human tTG gene is located on the 20th chromosome (20q11.2-q12).
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, apoptosisand extracellular matrixdevelopment
TG2 also has
GTPaseactivity: 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 sensitivityin which a cellular response to "Triticeae" glutens that are crosslinked to tTG are able to stimulate transglutaminase specific B-cellresponses 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.
Serologyfor 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.]
Use of tTG as a form of surgical glue is still experimental. It is also being studied as an attenuator of
metastasisin certain tumors.
* [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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