Tissue transglutaminase

Transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase)
Tissue transglutaminase drawn from PDB 1FAU.
Available structures
1kv3
Identifiers
Symbols	TGM2; TG2; TGC
External IDs	OMIM: 190196 MGI: 98731 HomoloGene: 3391
EC number	2.3.2.13
Gene ontology Molecular function • protein-glutamine gamma-glutamyltransferase activity • calcium ion binding • GTP binding • acyltransferase activity • transferase activity Cellular component • proteinaceous extracellular matrix • cytosol • membrane Biological process • G-protein coupled receptor protein signaling pathway • peptide cross-linking • positive regulation of cell adhesion
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7052	21817
Ensembl	ENSG00000198959	ENSMUSG00000037820
UniProt	P21980	Q3TLV2
RefSeq	NM_004613 (mRNA)	NM_009373 (mRNA)
	NP_004604 (protein)	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]

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 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.

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]

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]

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
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

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.

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 PDB Gallery 1kv3: HUMAN TISSUE TRANSGLUTAMINASE IN GDP BOUND FORM