Dyrk1a
Domain
The polyhistidine repeats act as targeting signals to nuclear speckles.
The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance its ability to phosphorylate the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).
Function
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:18938227, PubMed:22998443, PubMed:8631952, PubMed:9748265). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (By similarity). Plays an important role in double-strand breaks (DSBs) repair following DNA damage (By similarity). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (By similarity). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (By similarity). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (By similarity). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (PubMed:22767602). Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (PubMed:18938227).
Post-translational modifications
Can also autophosphorylate on serine and threonine residues (in vitro) (By similarity). Autophosphorylated on numerous tyrosine residues (PubMed:8631952).
Sequence Similarities
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
Tissue Specificity
Detected in brain (at protein level). Ubiquitous.
Cellular localization
- Nucleus speckle
Alternative names
Dyrk, Dyrk1a, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Dual specificity YAK1-related kinase, Protein kinase minibrain homolog, RP86, MNBH