title: Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions.
abstract: Transglutaminase 2 (TG2) is a multifunctional member of an enzyme family: it modifies glutamine residues by cross-linking proteins and incorporating primary amines into them, has protein disulphide isomerase and protein kinase activities, mediates trans-membrane signal transduction and interactions between cell surface proteins and the extracellular matrix. These unusual multiple roles encoded into one polypeptide chain suggest that genomic variations in the TGM2 gene should be limited. Indeed, the available information in databases shows that unlike in the case of most other transglutaminases there are no common single nucleotide polymorphisms in exons of human TGM2. We collected data on and produced some of the rare genetic variants of TGM2 by site directed mutagenesis and found that some were less stable than the most abundant (wild type) enzyme variant and the majority had deficient transamidating activity. Further studies are required to clarify the pathologic significance of these rare TGM2 alleles in the human population.
authors.affiliation: Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Egyetem tér 1, Debrecen 4012, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Király
authors.forename: Endre
authors.initials: E
authors.lastname: Barta
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004795:Enzyme Stability; D005353:Fibronectins / Q000737:chemistry; D019204:GTP-Binding Proteins; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017422:Sequence Analysis, DNA; D011503:Transglutaminases / Q000737:chemistry / Q000235:genetics*
chemical_list: D005353:Fibronectins; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins