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Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

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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.

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Acknowledgments

This work has been supported by grants from the Hungarian Scientific Research Fund (OTKA NI 67877), TAMOP-4.2.2-08/1/2008-0015 and TÁMOP 4.2.1./B-09/1/KONV-2010-0007 projects implemented through the New Hungary Development Plan, co-financed by the European Social Fund, an ETT grant from the Hungarian Ministry of Health, European Union MRTNCT-2006-036032 and MRTN-CT 2006-035624.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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

    Róbert Király, Endre Barta & László Fésüs

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  1. Róbert Király
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  2. Endre Barta
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  3. László Fésüs
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Correspondence to László Fésüs.

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Király, R., Barta, E. & Fésüs, L. Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions. Amino Acids 44, 215–225 (2013). https://doi.org/10.1007/s00726-011-1194-6

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  • DOI: https://doi.org/10.1007/s00726-011-1194-6

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