caa a22 4500 60617480X CHVBK 20210128100739.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00018-015-1909-z doi (NATIONALLICENCE)springer-10.1007/s00018-015-1909-z Physiological, pathological, and structural implications of non-enzymatic protein-protein interactions of the multifunctional human transglutaminase 2 [Elektronische Daten] [Kajal Kanchan, Mónika Fuxreiter, László Fésüs] Transglutaminase 2 (TG2) is a ubiquitously expressed member of an enzyme family catalyzing Ca2+-dependent transamidation of proteins. It is a multifunctional protein having several well-defined enzymatic (GTP binding and hydrolysis, protein disulfide isomerase, and protein kinase activities) and non-enzymatic (multiple interactions in protein scaffolds) functions. Unlike its enzymatic interactions, the significance of TG2's non-enzymatic regulation of its activities has recently gained importance. In this review, we summarize all the partners that directly interact with TG2 in a non-enzymatic manner and analyze how these interactions could modulate the crosslinking activity and cellular functions of TG2 in different cell compartments. We have found that TG2 mostly acts as a scaffold to bridge various proteins, leading to different functional outcomes. We have also studied how specific structural features, such as intrinsically disordered regions and embedded short linear motifs contribute to multifunctionality of TG2. Conformational diversity of intrinsically disordered regions enables them to interact with multiple partners, which can result in different biological outcomes. Indeed, ID regions in TG2 were identified in functionally relevant locations, indicating that they could facilitate conformational transitions towards the catalytically competent form. We reason that these structural features contribute to modulating the physiological and pathological functions of TG2 and could provide a new direction for detecting unique regulatory partners. Additionally, we have assembled all known anti-TG2 antibodies and have discussed their significance as a toolbox for identifying and confirming novel TG2 regulatory functions. Springer Basel, 2015 Transglutaminase 2 nationallicence Non-enzymatic interactions nationallicence Intrinsically disordered regions nationallicence TRANSDAB database nationallicence Scaffolding nationallicence Anti-TG2 antibodies nationallicence Kanchan Kajal Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4010, Debrecen, Hungary aut Fuxreiter Mónika MTA-DE Momentum Laboratory of Protein Dynamics, University of Debrecen, Debrecen, Hungary aut Fésüs László Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4010, Debrecen, Hungary aut Cellular and Molecular Life Sciences Springer Basel 72/16(2015-08-01), 3009-3035 1420-682X 72:16<3009 2015 72 18 https://doi.org/10.1007/s00018-015-1909-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1909-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanchan Kajal Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4010, Debrecen, Hungary aut NATIONALLICENCE 700 1- Fuxreiter Mónika MTA-DE Momentum Laboratory of Protein Dynamics, University of Debrecen, Debrecen, Hungary aut NATIONALLICENCE 700 1- Fésüs László Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4010, Debrecen, Hungary aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/16(2015-08-01), 3009-3035 1420-682X 72:16<3009 2015 72 18