Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Also known as: DYRK, DYRK1A, MNB, MNBH
Function
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Plays an important role in double-strand breaks (DSBs) repair following DNA damage. Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR). 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. May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (By similarity). This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity).
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- Kinase-like_dom_sf, PKc_DYR1A/1B, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS, Ser_Thr_dual-spec_kinase
- Functional cluster
- RNA-Polymerase II Transcription Factors
Experimental structures · PDB · 91
- 2VX3 X-ray 2.40A
- 2WO6 X-ray 2.50A
- 3ANQ X-ray 2.60A
- 3ANR X-ray 2.60A
- 4AZE X-ray 3.15A
- 4MQ1 X-ray 2.35A
- 4MQ2 X-ray 2.80A
- 4NCT X-ray 2.60A
- 4YLJ X-ray 2.58A
- 4YLK X-ray 1.40A
- 4YLL X-ray 1.40A
- 4YU2 X-ray 2.90A
- … and 79 more
A predicted model is available from AlphaFold.
Gene Ontology · 40
- GO:0030424 axon
- GO:0005737 cytoplasm
- GO:0005856 cytoskeleton
- GO:0030425 dendrite
- GO:0016607 nuclear speck
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:1990904 ribonucleoprotein complex
- GO:0003779 actin binding
- GO:0005524 ATP binding
- GO:0008092 cytoskeletal protein binding
- GO:0140857 histone H3T45 kinase activity
- GO:0042802 identical protein binding
- GO:0004715 non-membrane spanning protein tyrosine kinase activity
- GO:0004672 protein kinase activity
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
- GO:1990935 splicing factor binding
- GO:0048156 tau protein binding
- GO:0050321 tau-protein kinase activity
- GO:0003713 transcription coactivator activity
- GO:0015631 tubulin binding
- GO:0007623 circadian rhythm
- GO:0006351 DNA-templated transcription
- GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator
- GO:0031452 negative regulation of heterochromatin formation
- GO:0031115 negative regulation of microtubule polymerization
- GO:0007399 nervous system development
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0045893 positive regulation of DNA-templated transcription
- GO:2000781 positive regulation of double-strand break repair
- GO:0033120 positive regulation of RNA splicing
- GO:0046777 protein autophosphorylation
- GO:0006468 protein phosphorylation
- GO:0000381 regulation of alternative mRNA splicing, via spliceosome
- GO:1902003 regulation of amyloid-beta formation
- GO:1902996 regulation of neurofibrillary tangle assembly
Disease associations
- DYRK1A-related intellectual disability syndrome MONDO:0013578
Drugs targeting this protein · 1
- LORECIVIVINT inhibitor
Related proteins · sequence + function similarity
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 1.00
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 1.00
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 1.00
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 0.99
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 0.99
- Serine/threonine-protein kinase minibrain 0.82
- Dual specificity tyrosine-phosphorylation-regulated kinase mbk-2 0.80
- Dual specificity tyrosine-phosphorylation-regulated kinase mbk-2 0.80
- Dual specificity tyrosine-phosphorylation-regulated kinase mbk-1 0.80
- Dual specificity tyrosine-phosphorylation-regulated kinase mbk-1 0.79
- Dual specificity tyrosine-phosphorylation-regulated kinase 2 0.79
- Dual specificity protein kinase YAK1 homolog 0.78
Co-cited proteins · studied together in the literature
- Helicase ARIP4 1 shared papers
- Biotin--protein ligase 2 shared papers
- Dual specificity tyrosine-phosphorylation-regulated kinase 1A 3 shared papers
- Dual specificity tyrosine-phosphorylation-regulated kinase 4 1 shared papers
- E3 ubiquitin-protein ligase RNF169 1 shared papers
- Dual specificity tyrosine-phosphorylation-regulated kinase 2 3 shared papers
- Dual specificity tyrosine-phosphorylation-regulated kinase 1B 3 shared papers
- Dual specificity tyrosine-phosphorylation-regulated kinase 3 2 shared papers
- DDB1- and CUL4-associated factor 7 2 shared papers
- Cyclin-T1 1 shared papers
- Glycogen [starch] synthase, muscle 1 shared papers
- Proline-rich AKT1 substrate 1 1 shared papers
Literature · 30 cited papers
- R-loop resolution by ARIP4 helicase promotes androgen-mediated transcription induction. Sci. Adv. · 2024
- The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair. Sci. Rep. · 2019
- DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169. Cell Cycle · 2019
- Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature · 2018
- Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase. Mol. Cell · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors. Bioorg. Med. Chem. Lett. · 2013
- Dissection of the C-terminal region of E1A redefines the roles of CtBP and other cellular targets in oncogenic transformation. J. Virol. · 2013
- Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Structure · 2013
- Dual specificity kinase DYRK3 couples stress granule condensation/dissolution to mTORC1 signaling. Cell · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science · 2012
- … and 18 more in the literature graph
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