Tissue transglutaminase

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Tissue transglutaminase drawn from PDB 1FAU.
transglutaminase 2
Identifiers
Symbol	TGM2
HUGO	11778
Entrez	7052
OMIM	190196
RefSeq	NM_198951
UniProt	P21980
Other data
EC number	2.3.2.13
Locus	Chr. 20 q12

Tissue transglutaminase (TG2, tTG) is an enzyme (EC 2.3.2.13) of the transglutaminase family. Like other transglutaminases, it crosslinks proteins between an ε-N of a lysine residue and a glutamine residue in two protein chains, creating a 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^[1]

Contents 1 Genetics 2 Physiology 3 Role in disease 4 Diagnostic use 5 Therapeutic use 6 References

[edit] Genetics

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

[edit] Physiology

tTG is expressed ubiquitously. It requires calcium as a cofactor. Transcription is increased by retinoic acid. Amongst its many supposed functions, it appears to play a role wound healing, apoptosis and extracellular matrix development^[1]

[edit] Role in disease

tTG is best known for its link with coeliac disease, an allergy to gluten (wheat protein) in which the immune response crossreacts with tTG, leading to malabsorption.^[2]

Recent developments are the possible role of tTG in inflammation, degenerative diseases and tumour biology.^[1]

[edit] 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Serology for anti-tTG antibodies has superseded older serological tests (anti-endomysium, anti-gliadin and anti-reticulin) and has a strong sensitivity (99%) and specificity (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^[3]

[edit] 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 tumours.^[1]

[edit] References

1. ^ ^{a b c d} Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. Biochem J 2002;368:377-96. PMID 12366374.
2. ^ 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.
3. ^ 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.