Amino acid variants in human transglutaminase 2 and their biological relevance

A tétel rövid nézete
dc.contributor.advisorFésüs, László
dc.contributor.authorThangaraju, Kiruphagaran
dc.contributor.departmentMolekuláris sejt- és immunbiológia doktori iskolahu
dc.contributor.submitterdepDE--Általános Orvostudományi Kar -- Biokémiai és Molekuláris Biológiai Intézet
dc.date.accessioned2016-11-22T18:27:04Z
dc.date.available2016-11-22T18:27:04Z
dc.date.created2016hu_HU
dc.date.defended2016-12-05
dc.description.abstractTransglutaminases are a family of Ca2+-dependent protein transamidating and cross-linking enzymes involved in variety of biological processes. The Transglutaminase 2 (TG2) is an unique member of the transglutaminase family with several enzymatic, non-enzymatic activities and interacting partners and has been implicated in multiple disease states. In this study, novel amino acid clusters in human TG2 were identified and computational predictions revealed that these peptide sequences contribute to increasing stability of human TG2 and could potentially regulate vital functions. Based on the information from exome databases, TG2 non-synonymous single nucleotide variants were rare and under selective evolutionary constraint compared to other members of transglutaminase family. The damaging non-synonymous single nucleotide variants destabilize the protein structure and can influence vital functions. The transamidase and isopeptidase activities of TG2 were successfully separated by site-directed mutagenesis. Moreover, TG2 transamidase activity was shown to be involved in the formation of covalently cross-linked protein polymers and the potential role of isopeptidase activity in reversing the protein crosslinks was also demonstrated. Finally, a kinetic real-time protein based method to monitor the isopeptidase activity of TG2 was successfully developed.hu_HU
dc.description.correctorde
dc.format.extent107hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/232531
dc.language.isoenhu_HU
dc.subjecttransglutaminase 2hu_HU
dc.subjectbiochemical activities
dc.subjectnon-synonymous single nucleotide variants
dc.subjectnovel amino acid clusters
dc.subjectreal-time kinetic method
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.sciencefieldOrvostudományokhu
dc.titleAmino acid variants in human transglutaminase 2 and their biological relevancehu_HU
dc.title.translatedAmino acid variants in human transglutaminase 2 and their biological relevancehu_HU
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