title: Protein transamidation by transglutaminase 2 in cells: a disputed Ca2+-dependent action of a multifunctional protein.
abstract: Transglutaminase 2 (TG2) is the first described cellular member of an enzyme family catalyzing Ca(2+)-dependent transamidation of proteins. During the last two decades its additional enzymatic (GTP binding and hydrolysis, protein disulfide isomerase, protein kinase) and non-enzymatic (multiple interactions in protein scaffolds) activities, which do not require Ca(2+) , have been recognized. It became a prevailing view that TG2 is silent as a transamidase, except in extreme stress conditions, in the intracellular environment characterized by low Ca(2+) and high GTP concentrations. To counter this presumption a critical review of the experimental evidence supporting the role of this enzymatic activity in cellular processes is provided. It includes the structural basis of TG2 regulation through non-canonical Ca(2+) binding sites, mechanisms making it sensitive to low Ca(2+) concentrations, techniques developed for the detection of protein transamidation in cells and examples of basic cellular phenomena as well as pathological conditions influenced by this irreversible post-translational protein modification.
authors: Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
authors: Róbert
authors: R
authors: Király
authors: Mátéá
authors: M
authors: Demény
authors: László
authors: L
authors: Fésüs
mesh_terms: D000375:Aging / Q000502:physiology; D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000503:physiopathology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium