Figure 1.

Dual-specificity tyrosine-regulated kinase (DYRK) protein kinases: primary structure and expression. (A) Scheme of the mammalian family of DYRKs, indicating their phylogenic relationships, degree of homology and protein domains. The catalytic domain (KINASE) and the DYRK homology box (DH) are common to all members of the family. Class I DYRKs have two nuclear localization signals (NLSs) (NLS1 and NLS2) and a proline-, glutamic acid-, serine- and threonine-rich (PEST) motif. DYRK1A also includes a tract of 13 consecutive histidine residues (His) and a region enriched in serine/threonine residues (S/T) at the C-terminus. Class II DYRKs have a common structure, with the characteristic N-terminal autophosphorylation accessory (NAPA) domain at the N-terminus. In the case of DYRK2 and DYRK4, functional NLSs have been described within the noncatalytic N-terminus. (B) The expression of human DYRKs based on the Genotype-Tissue Expression (GTEx) data represented as the median TPMs (transcripts per million: GTEx Analysis Release V8, www.gtexportal.org/home, dbGaP Accession phs000424.v8.p2). Tissues represented in the tumor data in Table S1 were chosen (brain: cortex; cervix: ectocervix; colon: sigmoid colon; esophagus; mucosa, kidney: cortex; skin: suprapubic—not sun-exposed).