Transglutaminase 5 is regulated by guanine-adenine nucleotides

Eleonora Candi, Andrea Paradisi, Alessandro Terrinoni, Valentina Pietroni, Sergio Oddi, Bruno Cadot, Vishwanath Jogini, Muthuraman Meiyappan, Jon Clardy, Alessandro Finazzi-Agro, Gerry Melino

Research output: Contribution to journalArticlepeer-review


Transglutaminases (TGases) are Ca2+-dependent enzymes capable of catalysing transamidation of glutamine residues to form intermolecular isopeptide bonds. Nine distinct TGases have been described in mammals, and two of them (types 2 and 3) are regulated by GTP/ATP. TGase2 hydrolyses GTP and is therefore a bifunctional enzyme. In the present study, we report that TGase5 is also regulated by nucleotides. We have identified the putative TGase5 GTP-binding pocket by comparative amino acid sequence alignment and homology-derived three-dimensional modelling. GTP and ATP inhibit TGase5 cross-linking activity in vitro, and Ca2+ is capable of completely reversing this inhibition. In addition, TGase5 mRNA is not restricted to epidermal tissue, but is also present in different adult and foetal tissues, suggesting a role for TGase5 outside the epidermis. These results reveal the reciprocal actions of Ca2+ and nucleotides with respect to TGase5 activity. Taken together, these results indicate that TGases are a complex family of enzymes regulated by calcium, with at least three of them, namely TGase2, TGase3 and TGase5, also being regulated by ATP and GTP.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalBiochemical Journal
Issue number1
Publication statusPublished - Jul 1 2004


  • Apoptosis
  • GTP
  • GTPase activity
  • Transglutaminase

ASJC Scopus subject areas

  • Biochemistry


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