DYRK1A Protein, Human (Active)

DYRK1A, a dual-specificity kinase endowed with both serine/threonine and tyrosine kinase activities, plays a pivotal role in various cellular processes. It exhibits a substrate preference for proline at position P+1 and arginine at position P-3, showcasing its specificity in substrate recognition. In the context of DNA damage response, DYRK1A emerges as a key participant in double-strand breaks repair, phosphorylating RNF169 to enhance its capability to impede TP53BP1 accumulation at DSB sites, thereby facilitating homologous recombination repair. Moreover, DYRK1A acts as a positive regulator of transcription by functioning as a CTD kinase, orchestrating the phosphorylation of the C-terminal domain of the large subunit of RNA polymerase II (POLR2A). This kinase may contribute to a signaling pathway governing nuclear functions related to cell proliferation and modulates alternative splicing through the phosphorylation of the splice factor SRSF6. With pro-survival functions, DYRK1A negatively regulates apoptosis, promoting cell survival under genotoxic stress by phosphorylating SIRT1, consequently inhibiting p53/TP53 activity. Additionally, DYRK1A targets SEPTIN4, SEPTIN5, and SF3B1 for phosphorylation at 'Thr-434,' further expanding its regulatory repertoire.