Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Protein-Glutamine Gamma-Glutamyltransferase

  • Ivone M. Martins
  • Altino ChoupinaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101758


Historical Background

Transglutaminases (TGs) are a family of enzymes (EC that catalyze the formation of amide bonds between proteins to form insoluble cross-linked protein aggregates that are resistant to chemicals, detergents, and proteases degradation (Griffin et al. 2002; Yokoyama et al. 2004).

TG activity was first observed in 1957 by Clarke et al. (1957), when they found an enzyme with transamidating properties extracted from guinea pig liver. Only in 1959 the name transglutaminase was assigned by Waelsch and collaborators (Mycek et al. 1959), in order to distinguish this enzymatic activity from that of other enzymes with similar activity.

TGs catalyzes posttranslational cross-link reactions between two substrates that can be two proteins or two residues of...
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  1. Ando H, Adachi M, Umeda K, Matsuura A, Nonaka M, Uchio R, Tanaka H, Motoki M. Purification and characteristics of a novel transglutaminase derived from microorganisms. Agric Biol Chem. 1989;53:2613–7.Google Scholar
  2. Beninati S, Piacentini M. The transglutaminase family: an overview: minireview article. Amino Acids. 2004;26(4):367–72.PubMedGoogle Scholar
  3. Clarke DD, Neidle A, Sarkar NK, Waelsch H. Metabolic activity of protein amide groups. Arch Biochem Biophys. 1957;71(1):277–9.CrossRefPubMedGoogle Scholar
  4. Collighan RJ, Griffin M. Transglutaminase 2 cross-linking of matrix proteins: biological significance and medical applications. Amino Acids. 2009;36(4):659–70.CrossRefPubMedGoogle Scholar
  5. Connellan JM, Chung SI, Whetzel NK, Bradley LM, Folk JE. Structural properties of guinea pig liver transglutaminase. J Biol Chem. 1971;246(4):1093–8.PubMedGoogle Scholar
  6. Cortez J, Bonner PL, Griffin M. Transglutaminase treatment of wool fabrics leads to resistance to detergent damage. J Biotechnol. 2005;116(4):379–86.CrossRefPubMedGoogle Scholar
  7. Del Duca S, Serafini-Fracassini D. Transglutaminases of higher, lower plants and fungi. Prog Exp Tumor Res. 2005;38:223–47.CrossRefPubMedGoogle Scholar
  8. Della Mea M, Caparros-Ruiz D, Claparols I, Serafini-Fracassini D, Rigau J. AtPng1p: the first plant transglutaminase. Plant Physiol. 2004;135(4):2046–54.CrossRefPubMedGoogle Scholar
  9. Facchiano F, Facchiano A, Facchiano AM. The role of transglutaminase-2 and its substrates in human diseases. Front Biosci. 2006;11:1758–73.CrossRefPubMedGoogle Scholar
  10. Folk JE, Chung SI. Molecular and catalytic properties of transglutaminases. Adv Enzymol Relat Areas Mol Biol. 1973;38:109–91.PubMedGoogle Scholar
  11. Folk JE, Cole PW. Mechanism of action of guinea pig liver transglutaminase. I. Purification and properties of the enzyme: identification of a functional cysteine essential for activity. J Biol Chem. 1966;241(23):5518–25.PubMedGoogle Scholar
  12. Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature’s biological glues. Biochem J. 2002;368(Pt 2):377–96.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Gundemir S, Colak G, Tucholski J, Johnson GV. Transglutaminase 2: a molecular Swiss army knife. Biochim Biophys Acta. 2012;1823(2):406–19.CrossRefPubMedGoogle Scholar
  14. Kanaji T, Ozaki H, Takao T, Kawajiri H, Ide H, Motoki M, Shimonishi Y. Primary structure of microbial transglutaminase from Streptoverticillium sp. strain s-8112. J Biol Chem. 1993;268(16):11565–72.PubMedGoogle Scholar
  15. Kuraishi C, Yamazaki K, Susa Y. Transglutaminase: its utilization in the food industry. Food Rev Intl. 2001;17(2):221–46.CrossRefGoogle Scholar
  16. Lentini A, Abbruzzese A, Provenzano B, Tabolacci C, Beninati S. Transglutaminases: key regulators of cancer metastasis. Amino Acids. 2013;44(1):25–32.CrossRefPubMedGoogle Scholar
  17. Lorand L, Graham RM. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol. 2003;4(2):140–56.CrossRefPubMedGoogle Scholar
  18. Mehta K. Mammalian transglutaminases: a family portrait. Prog Exp Tumor Res. 2005;38:1–18.CrossRefPubMedGoogle Scholar
  19. Mycek MJ, Clarke DD, Neidle A, Waelsch H. Amine incorporation into insulin as catalyzed by transglutaminase. Arch Biochem Biophys. 1959;84:528–40.CrossRefPubMedGoogle Scholar
  20. Porta R, Giosafatto CV, di Pierro P, Sorrentino A, Mariniello L. Transglutaminase-mediated modification of ovomucoid: effects on its trypsin inhibitory activity and antigenic properties. Amino Acids. 2013;44(1):285–92.CrossRefPubMedGoogle Scholar
  21. Serafini-Fracassini D, Del Duca S. Transglutaminases: widespread cross-linking enzymes in plants. Ann Bot. 2008;102(2):145–52.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Serafini-Fracassini D, Della Mea M, Tasco G, Casadio R, Del Duca S. Plant and animal transglutaminases: do similar functions imply similar structures? Amino Acids. 2009;36(4):643–57.CrossRefPubMedGoogle Scholar
  23. Shi YG, Qian L, Zhang N, Han CR, Liu Y, Zhang YF, Ma YQ. Changes in morphology and activity of transglutaminase following cross-linking and immobilization on a polypropylene microporous membrane. Molecules. 2011;16(12):10046–58.CrossRefPubMedGoogle Scholar
  24. Tabolacci C, Lentini A, Provenzano B, Beninati S. Evidences for a role of protein cross-links in transglutaminase-related disease. Amino Acids. 2012;42(2–3):975–86.CrossRefPubMedGoogle Scholar
  25. Teixeira LS, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M. Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engineering. Biomaterials. 2012;33(5):1281–90.CrossRefPubMedGoogle Scholar
  26. Yokoyama K, Nio N, Kikuchi Y. Properties and applications of microbial transglutaminase. Appl Microbiol Biotechnol. 2004;64(4):447–54.CrossRefPubMedGoogle Scholar
  27. Zeugolis DI, Panengad PP, Yew ES, Sheppard C, Phan TT, Raghunath M. An in situ and in vitro investigation for the transglutaminase potential in tissue engineering. J Biomed Mater Res A. 2010;92(4):1310–20.PubMedGoogle Scholar
  28. Zhang J, Wang S, Huang W, Bennett DA, Dickson DW, Wang D, Wang R. Tissue transglutaminase and its product isopeptide are increased in alzheimer’s disease and APPswe/PS1dE9 double transgenic mice brains. Mol Neurobiol. 2016;53(8):5066–78.CrossRefPubMedGoogle Scholar
  29. Zhu Y, Rinzema J, Tramper J, Bol J. Microbial transglutaminase: a review of its production and application in food processing. Appl Microbiol Biotechnol. 1995;44(3–4):277–82.CrossRefGoogle Scholar
  30. Zhu Y, Tramper J. Novel applications for microbial transglutaminase beyond food processing. Trends Biotechnol. 2008;26(10):559–65.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.CEB - Centre of Biological EngineeringUniversity of MinhoBragaPortugal
  2. 2.CIMO-Mountain Research CenterAgricultural College of Bragança, Polytechnic Institute of BragançaBragançaPortugal