Tissue transglutaminase

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Transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase)
Tissue transglutaminase drawn from PDB 1FAU.
Available structures: 1kv3
Identifiers
Symbol(s) TGM2; TG2; TGC
External IDs OMIM: 190196 MGI: 98731 HomoloGene: 3391
EC number 2.3.2.13
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 7052 21817
Ensembl ENSG00000198959 ENSMUSG00000037820
Uniprot P21980 Q3TLV2
Refseq NM_004613 (mRNA)
NP_004604 (protein)		 NM_009373 (mRNA)
NP_033399 (protein)
Location Chr 20: 36.19 - 36.23 Mb Chr 2: 157.81 - 157.84 Mb
Pubmed search [1] [2]

{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]

Contents

[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. Amongst 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] Beside 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]

[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. ^ Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 2002;27:534-9. PMID 12368090.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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
  7. ^ 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.

[edit] External links

  • Endomysial antibodies
  • A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an interactive transglutaminase substrate database.
v • d • e
Transferases: acyltransferases (EC 2.3)
2.3.1: other than amino-acyl groups
(mostly acetyltransferases)
2.3.2 - Aminoacyltransferases
2.3.3 - converted into alkyl on transfer
v • d • e
Antigens: Autoantigens
Dehydrogenase
Transglutaminase
Epidermal transglutaminase - Tissue transglutaminase
Nucleoporins
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