9krj

Structural highlights

Function

DYR1A_MOUSE Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:18938227, PubMed:20123978). 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 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (PubMed:20167603). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (PubMed:20167603). This in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (PubMed:18938227).[UniProtKB:Q13627][UniProtKB:Q63470]^{[1] [2] [3]}

References

1. ↑ Sitz JH, Baumgärtel K, Hämmerle B, Papadopoulos C, Hekerman P, Tejedor FJ, Becker W, Lutz B. The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience. 2008 Dec 2;157(3):596-605. PMID:18938227 doi:10.1016/j.neuroscience.2008.09.034
2. ↑ Kurabayashi N, Hirota T, Sakai M, Sanada K, Fukada Y. DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Mol Cell Biol. 2010 Apr;30(7):1757-68. doi: 10.1128/MCB.01047-09. Epub 2010 Feb, 1. PMID:20123978 doi:http://dx.doi.org/10.1128/MCB.01047-09
3. ↑ Guo X, Williams JG, Schug TT, Li X. DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem. 2010 Apr 23;285(17):13223-32. doi: 10.1074/jbc.M110.102574. Epub, 2010 Feb 18. PMID:20167603 doi:http://dx.doi.org/10.1074/jbc.M110.102574