Summary
The “Down syndrome critical region” of human chromosome 21 has been defined based on the analysis of rare cases of partial trisomy 21. Evidence is accumulating that DYRK1A, one of the 20 genes located in this region, is an important candidate gene involved in the neurobiological alterations of Down syndrome. Both the structure of the DYRK1A gene and the sequence of the encoded protein kinase are highly conserved in evolution. The protein contains a unique assembly of structural motifs outside the catalytic domain, including a nuclear localization signal, a PEST region, and a repeat of 13 consecutive histidines. MNB/DYRK1A* and related kinases are unique among serine/threonine-specific protein kinases in that their activity depends on tyrosine autophosphorylation in the catalytic domain. Also, evidence is accumulating that mRNA levels of MNB/DYRK1A are subject to tight regulation. A number of putative substrates of MNB/DYRK1A have emerged in the recent years, the majority of them being transcription factors. Although the function of MNB/DYRK1A in intracellular signalling and regulation of cell function is still poorly defined, current evidence suggests that the kinase may play a role in the regulation of gene expression.
DYRK1A is the official gene symbol approved by the HUGO Gene Nomenclature Committee. Nevertheless, MNB has been also frequently used by several authors. Thus, we use MNB/DYRK1A in this review to refer to these orthologous genes in contrast to other members of the DYRK family of protein kinases.
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Galceran, J., de Graaf, K., Tejedor, F.J., Becker, W. (2003). The MNB/DYRK1A protein kinase: Genetic and biochemical properties. In: Lubec, G. (eds) Advances in Down Syndrome Research. Journal of Neural Transmission Supplement 67, vol 67. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6721-2_12
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DOI: https://doi.org/10.1007/978-3-7091-6721-2_12
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