Tissue transglutaminase (abbreviated as TG2 or tTG) is an enzyme (EC 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.[1]
[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 for transamidation activity. Transcription is increased by retinoic acid. Among its many supposed functions, it appears to play a role in wound healing, apoptosis, and extracellular matrix development[1]
TG2 also has GTPase activity: In the presence of GTP, it suggested to function as a G protein participating in signaling processes.[2] Besides its transglutaminase activity, TG2 is proposed to also act as kinase,[3] and protein disulfide isomerase,[4] and deamidase.[5] This latter activity is important in the deamidation of gliadin peptides, thus playing important role in the pathology of coeliac disease.
[edit] 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.[6]
Recent studies suggest that tTG plays a role in inflammation, degenerative diseases, and tumor 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Serology for anti-tTG antibodies has superseded older serological tests (anti-endomysium, anti-gliadin, and anti-reticulin) and has a strong sensitivity (99%) and specificity (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.[7]
[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 tumors.[1]
| Mouse Mutant Alleles for Tgm2 |
| Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the MGI |
Tgm2 |
| Mutant Mouse Embryonic Stem Cell Clones. These are the known targeted mutations for this gene in a mouse. |
Tgm2tm1a(KOMP)Wtsi |
| Example structure of targeted conditional mutant allele for this gene |
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| These Mutant ES Cells can be studied directly or used to generate mice with this gene knocked out. Study of these mice can shed light on the function of Tgm2: see Knockout mouse |
[edit] References
- ^ a b c d Griffin M, Casadio R, Bergamini CM (December 2002). "Transglutaminases: nature's biological glues". Biochem. J. 368 (Pt 2): 377–96. doi:10.1042/BJ20021234. PMC 1223021. PMID 12366374. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223021.
- ^ Fesus L, Piacentini M (October 2002). "Transglutaminase 2: an enigmatic enzyme with diverse functions". Trends Biochem. Sci. 27 (10): 534–9. PMID 12368090.
- ^ Mishra S, Murphy LJ (June 2004). "Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 as an insulin-like growth factor-binding protein-3 kinase". J. Biol. Chem. 279 (23): 23863–8. doi:10.1074/jbc.M311919200. PMID 15069073.
- ^ Hasegawa G, Suwa M, Ichikawa Y, Ohtsuka T, Kumagai S, Kikuchi M, Sato Y, Saito Y (August 2003). "A novel function of tissue-type transglutaminase: protein disulphide isomerase". Biochem. J. 373 (Pt 3): 793–803. doi:10.1042/BJ20021084. PMC 1223550. PMID 12737632. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223550.
- ^ Sakly W, Thomas V, Quash G, El Alaoui S (December 2006). "A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity". Clin. Exp. Immunol. 146 (3): 550–8. doi:10.1111/j.1365-2249.2006.03236.x. PMC 1810403. PMID 17100777. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1810403.
- ^ Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D (July 1997). "Identification of tissue transglutaminase as the autoantigen of celiac disease". Nat. Med. 3 (7): 797–801. doi:10.1038/nm0797-797. PMID 9212111.
- ^ Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, Fasano A, Ventura A, Not T (May 2000). "Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease". Am. J. Gastroenterol. 95 (5): 1253–7. doi:10.1111/j.1572-0241.2000.02018.x. PMID 10811336.
[edit] External links
- Endomysial antibodies
- A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an interactive transglutaminase substrate database.
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PDB gallery
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1kv3: HUMAN TISSUE TRANSGLUTAMINASE IN GDP BOUND FORM
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