Fig. 9

Role of the CMGC insert in the folding and maturation of the DYRK1 kinase domain. Cartoon illustration of DYRK1 domain folding and activation. Proper folding is influenced by the sequence of the CMGC insert and the cellular environment. During maturation, the kinase adopts a flexible, partially folded conformation that allows intramolecular cis-autophosphorylation of the conserved activation loop tyrosine (indicated by the red Y), a prerequisite for acquiring full catalytic activity as a serine/threonine kinase.