title: Transglutaminase 5 is regulated by guanine-adenine nucleotides.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
authors.forename: Andrea
authors.initials: A
authors.lastname: Paradisi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terrinoni
authors.forename: Valentina
authors.initials: V
authors.lastname: Pietroni
authors.forename: Sergio
authors.initials: S
authors.lastname: Oddi
authors.forename: Bruno
authors.initials: B
authors.lastname: Cadot
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Jogini
authors.forename: Muthuraman
authors.initials: M
authors.lastname: Meiyappan
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
authors.forename: Alessandro
authors.initials: A
authors.lastname: Finazzi-Agro
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016415:Sequence Alignment / Q000379:methods; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D019881:Aminoacyltransferases; C023175:transamidases; C418703:transglutaminase 5; D000091345:Protein Glutamine gamma Glutamyltransferase 2; C498712:TGM3 protein, human; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D002118:Calcium