title: Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function.
abstract: Transglutaminase 2 (TGM2) is a unique protein of a nine member family with several enzymatic and non-enzymatic activities and interacting partners. Its physiological and pathological roles, however, are not fully understood. Comparative genomic and computational analysis reported here have revealed phylogenetic changes of TGM2 resulting in novel amino acid clusters in humans and other primates, which may impact secondary structure and increase protein stability. These clusters are located in intrinsically disordered regions and via short linear motifs influence interactions with TGM2 partners directly, or through post-translation modification (phosphorylation and N-glycosylation sites). Our data shed new light on the structural background and evolution of TGM2 multi-functionality and points to so far unrevealed biological roles of the enzyme.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary.
authors.forename: Kiruphagaran
authors.initials: K
authors.lastname: Thangaraju
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Király
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary.
authors.forename: János András
authors.initials: JA
authors.lastname: Mótyán
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary.|MTA-DE Momentum Laboratory of Protein Dynamics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Viktor Attila
authors.initials: VA
authors.lastname: Ambrus
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary.|MTA-DE Momentum Laboratory of Protein Dynamics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Mónika
authors.initials: M
authors.lastname: Fuxreiter
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary. fesus@med.unideb.hu.|MTA-DE Stem Cell, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. fesus@med.unideb.hu.
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D011503:Transglutaminases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D064267:Intrinsically Disordered Proteins; D007527:Isoenzymes; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Intrinsically disordered regions; Novel amino acid clusters; Protein stability; Short linear motifs; Transglutaminase 2