Transglutaminases and their substrates in biology and human diseases: 50 years of growing

Abstract

Transglutaminase is an enzyme able to play more than one enzymatic action, acting on a variety of different substrates. The growth of knowledge about the members of the enzyme transglutaminase's family and its substrates since the last 50 years indicates a large interest and curiosity about this protein, whose function and structure was, but still is, an important object of research. On the other hand, the involvement in a number of human diseases together with the lack of knowledge about the biological functions played by some of the most studied members of this family, make this enzyme a fascinating field of study. The history of this enzyme and its substrates, whose cross-linking action was reported for the first time 50 years ago, suggests that an effort to increase knowledge and communication among researchers is required. To achieve this important result, 10 years ago an internet web page called worldwide happening around transglutaminase (WHAT) was created. Driven by these experiences, novel points-of-view to look at Transglutaminase and its substrates may be identified.

Transglutaminase 2 ablation leads to mitophagy impairment associated with a metabolic shift towards aerobic glycolysis

“…Since the discovery of TG2 in 1957, 7 a large number of its substrates have been identified in intracellular compartments as well as on the cell surface and in the extracellular matrix. 8,9 A peculiar aspect of TG2 biology is its multifunctionality, this being dictated by marked changes in the enzyme's 3-D structure. In fact, under physiological conditions the TG2 transamidating activities are inhibited by the binding of GTP, GDP and ATP that constrains the protein in the 'closed' conformation; 10 in contrast, the transamidating activities are dependent on Ca 2 þ activation that shifts TG2 to the 'open' conformation, thereby unmasking the enzyme's active centre.…”

'Collodion baby': Presentation of a rare form of familial lamellar ichthyosis

“…Трансглутаминаза 1 је веома важан ензим одговоран за унакрсно повезивање епидермалних протеина током формирања и сазревања корнеалног слоја. Овај ген је лоциран на хромозому 14q11.2 и кодира ензим трансглутаминазу 1 (ТGМ 1) и један је од три трансглутаминазе које се налазе у епидерму (11). Мутација ТGМ 1 је најчешћи узрок настанка Ichthyosis lamellaris (55% у Америци, 85% у Норвешкој) (12).…”

“…колоидном мембраном и имају очне поремећаје и/или алопецију постоји четири пута већи ризик да имају ТGМ 1 мутацију (11,14). Ређе је ова болест повезана са мутацијама других гена: ABCA12 (2q34), NIPAL4 (5q33), CYP4F22 (19p13.12), ALOXE3-ALOX12B (17p13) (11)(12)(13)(14)(15)(16)(17).…”

Screening of substrate peptide sequences for tissue-type transglutaminase (TGase 2) using T7 phage cDNA library

“…So far, several approaches have revealed substrates for TGases by proteomics analyses of cross-linked/polymerized products, affinity purification using labeled primary amines, and screening from peptide display (Orru et al 2003;Lee et al 1992;Ikura et al 1998;Ichikawa et al 2008;Sugimura et al 2006;Keresztessy et al 2006). Based on the results of the studies described above, database for substrates and their sequences are available on the web site and summarized as several publications (Csosz et al 2009;Esposito and Caputo 2005;Facchiano and Facchiano 2009). Although much information has been accumulated, researches to identify novel substrates are still ongoing.…”