DYRK1A Antibody #2771

The DYRK family includes several dual-specificity tyrosine-phosphorylated and regulated kinases capable of phosphorylating proteins at both Tyr and Ser/Thr residues (1). The DYRK family was identified based on homology to the yeast Yak1 (2) and the Drosophila minibrain (mnb) kinases (3). Seven mammalian isoforms have been discovered, including DYRK1A, DYRK1B, DYRK1C, DYRK2, DYRK3, DYRK4, and DYRK4B. Differences in substrate specificity, expression, and subcellular localization are seen across the DYRK family (4,5). All DYRK proteins have a Tyr-X-Tyr motif in the catalytic domain activation loop; phosphorylation of the second Tyr residue (e.g. Tyr312 of DYRK1A) is necessary for kinase activity. DYRKs typically autophosphorylate the Tyr residue within their activation loop, but phosphorylate substrates at Ser and Thr residues (1,6).
DYRK1A phosphorylates serine and threonine residues within a RPX(S/T)P consensus sequence. Substrates include transcription factors such as FoxO1 and cAMP response element-binding proteins such as NFAT (7,8). DYRK1A is ubiquitously expressed in fetal and adult tissues. Transgenic mice with multiple copies of DYRK1A exhibit learning and motor defects suggesting that it is a dosage-sensitive gene (9). The DYRK1A gene localizes to chromosome 21q22.2, a region implicated in Down syndrome, and may contribute to pathological traits observed in chromosome 21 trisomy (10).