Affinage

DYRK2

Dual specificity tyrosine-phosphorylation-regulated kinase 2 · UniProt Q92630

Length
601 aa
Mass
66.7 kDa
Annotated
2026-06-09
75 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYRK2 is a dual-specificity serine/threonine kinase that acts as a master priming kinase, marking diverse substrates for processive phosphorylation and ubiquitin-mediated degradation to control apoptosis, cell-cycle progression, EMT, ciliary signaling, and protein synthesis (PMID:17349958, PMID:19287380, PMID:22307329). In the DNA damage response it translocates to the nucleus and directly phosphorylates p53 at Ser46 to induce p53AIP1-dependent apoptosis (PMID:17349958); its nuclear pool is gated by competing modifications, with ATM phosphorylation at Thr33/Ser369 freeing it from MDM2-mediated degradation, while SIAH2 and USP28 oppose to set DYRK2 abundance and thereby p53-Ser46 output (PMID:19965871, PMID:22878263, PMID:40858801). DYRK2 serves as the kinase-bearing scaffold of the EDD-DDB1-VPRBP (EDVP) E3 ligase, a function genetically separable from catalysis; it phosphorylates and primes substrates including katanin p60, TERT, and the centriolar protein CP110 for EDVP-mediated ubiquitination (PMID:19287380, PMID:23362280, PMID:28242748). As a priming kinase upstream of GSK3β and βTrCP, DYRK2 phosphorylates c-Jun, c-Myc, Snail, and eIF2Bε to drive their proteasomal degradation, thereby restraining G1/S transition and proliferation, suppressing EMT, and limiting protein synthesis and cardiomyocyte growth (PMID:22307329, PMID:23791882, PMID:31209060, PMID:24023715). DYRK2 phosphorylates TBK1 at Ser527 to prime its K48-linked ubiquitination and degradation, dampening type I interferon induction (PMID:26407194). It also functions as a ciliary kinase that phosphorylates GLI2/GLI3 downstream of Smoothened, dissociating them from SUFU to activate Hedgehog signaling during skeletal and lung development (PMID:32758357, PMID:38968120). Additional characterized substrates and partners include CDC25A and CDK1 (cell-cycle control), STIM1 and 4E-BP1, NAE1 (cullin neddylation and genome stability), and HSF1 (proteotoxic stress survival) (PMID:34363019, PMID:35439114, PMID:35582972, PMID:33268814, PMID:41933287). DYRK2 scaffold-disrupting variants identified in CAKUT patients link its EDVP function to kidney development (PMID:40777246).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2007 High

    Established DYRK2 as a direct effector of the DNA damage apoptotic program by identifying p53-Ser46 as a physiological substrate, answering how genotoxic stress couples to apoptotic p53 output.

    Evidence In vitro kinase assay, Ser46 phospho-specific detection, siRNA, nuclear translocation by fractionation/IF, apoptosis assays

    PMID:17349958

    Open questions at the time
    • Upstream signal triggering nuclear translocation not defined here
    • Did not address non-apoptotic DYRK2 functions
  2. 2009 High

    Revealed a non-catalytic role: DYRK2 acts as the scaffold organizing the EDD-DDB1-VPRBP E3 ligase, while its kinase activity primes substrates such as katanin p60 for degradation, separating scaffold from catalytic functions.

    Evidence Reciprocal Co-IP, siRNA, ubiquitination assay, kinase-dead mutant dissection

    PMID:19287380

    Open questions at the time
    • Full substrate repertoire of EDVP complex not defined
    • Stoichiometry/architecture of complex not resolved
  3. 2009 High

    Defined how nuclear DYRK2 abundance is controlled, showing ATM phosphorylation (Thr33/Ser369) dissociates DYRK2 from MDM2 to stabilize it for the p53 response.

    Evidence Co-IP, proteasome inhibition, phospho-site mutagenesis, siRNA, fractionation

    PMID:19965871

    Open questions at the time
    • Whether ATM phosphorylates DYRK2 directly vs indirectly
    • Quantitative contribution to apoptotic threshold unclear
  4. 2012 High

    Identified the priming-kinase paradigm for proliferation control, showing DYRK2 primes c-Jun and c-Myc for GSK3β/βTrCP degradation to restrain G1 and proliferation.

    Evidence siRNA, phospho-Western, cell-cycle analysis, xenograft, epistasis by co-knockdown

    PMID:22307329

    Open questions at the time
    • Phospho-sites on c-Jun/c-Myc not fully mapped here
    • Context dependence across cell types not addressed
  5. 2012 High

    Showed DYRK2 itself is regulated by SIAH2-mediated degradation and reciprocally phosphorylates SIAH2, linking DYRK2 stability to hypoxia and HIF-1α signaling.

    Evidence Co-IP, in vitro kinase assay, phospho-mutants, ubiquitination assay, fractionation, siRNA

    PMID:22878263

    Open questions at the time
    • In vivo relevance of SIAH2-DYRK2 axis under hypoxia not established
    • Functional consequence of each SIAH2 phospho-site unclear
  6. 2013 High

    Extended the priming-kinase role to EMT and telomere maintenance, showing DYRK2 primes Snail for degradation and phosphorylates TERT for EDVP-mediated, G2/M-restricted degradation.

    Evidence siRNA, Western for substrate stability, invasion/telomerase assays, in vitro kinase assay, cell-cycle synchronization, xenograft

    PMID:23362280 PMID:23791882

    Open questions at the time
    • Snail study did not show direct in vitro kinase assay
    • Cell-cycle gating mechanism for TERT phosphorylation not defined
  7. 2014 Medium

    Showed DYRK2 priming feeds non-GSK3β degradation pathways, phosphorylating hPXR to enable UBR5-mediated degradation, broadening the E3-ligase partnerships it serves.

    Evidence Kinome-wide siRNA screen, MS, Co-IP, ubiquitination assay, knockdown rescue

    PMID:24438055

    Open questions at the time
    • hPXR phospho-sites not mapped
    • Physiological/pharmacological relevance not tested in vivo
  8. 2015 High

    Placed DYRK2 in innate antiviral signaling, showing TBK1-Ser527 phosphorylation primes NLRP4/DTX4-mediated K48 ubiquitination and TBK1 degradation to suppress type I interferon.

    Evidence Co-IP, in vitro kinase assay, phospho-site mutagenesis, ubiquitination assay, siRNA, viral infection

    PMID:26407194

    Open questions at the time
    • Upstream regulation of DYRK2 during infection unknown
    • In vivo antiviral phenotype not established here
  9. 2017 High

    Defined CP110 as an EDVP substrate and Cep78 as a complex inhibitor acting at the ubiquitin-transfer step, linking the DYRK2-EDVP axis to centriole length and cilia assembly.

    Evidence Co-IP, in vitro kinase assay, ubiquitination assay, RNAi, centrosome/cilia imaging

    PMID:28242748

    Open questions at the time
    • How Cep78 selectively blocks transfer mechanistically unclear
    • Physiological signals controlling CP110 turnover unknown
  10. 2017 Medium

    Connected DYRK2 to double-strand break repair, showing its RNF8 interaction is required for γ-H2AX monoubiquitination, 53BP1 foci, and homologous recombination.

    Evidence High-throughput screen, Co-IP, siRNA, γ-H2AX ubiquitination assay, HR reporter, foci imaging

    PMID:28194753

    Open questions at the time
    • Whether DYRK2 phosphorylates RNF8 or another DDR factor unclear
    • Single lab, no reciprocal in vivo validation
  11. 2019 High

    Resolved a regulatory hierarchy on Snail, showing p38 MAPK phosphorylation at Ser107 suppresses DYRK2 priming at Ser104, controlling whether Snail is degraded.

    Evidence In vitro kinase assay, phospho-site mutagenesis, Co-IP, ubiquitination assay

    PMID:31209060

    Open questions at the time
    • In vivo relevance of p38-DYRK2 antagonism not tested
    • Generalizability to other DYRK2 substrates unclear
  12. 2019 Medium

    Embedded DYRK2 in a transcriptional circuit in leukemia stem cells, showing KLF4 represses DYRK2 and that restoring DYRK2 depletes c-Myc and activates p53 to impair self-renewal.

    Evidence Klf4 conditional KO mouse, protein quantification, SIAH2 small-molecule inhibitor, colony/sphere assays

    PMID:31515251

    Open questions at the time
    • Mechanistic link partly inferred from known substrates
    • Direct vs indirect DYRK2 effects on p53 in this context not dissected
  13. 2020 Medium

    Identified DYRK2 as a positive regulator of the proteotoxic stress response, phosphorylating HSF1 to sustain its nuclear stability and transcriptional activity in TNBC.

    Evidence siRNA, phospho-Western, HSF1 activity assays, proteotoxic stress sensitivity

    PMID:33268814

    Open questions at the time
    • HSF1 phospho-sites not defined
    • Whether this is degradative or stabilizing priming unclear
  14. 2020 High

    Established DYRK2 as a ciliogenesis-related kinase required for Hedgehog signaling in vivo, with loss causing skeletal defects and abnormal ciliary morphology and Hh trafficking.

    Evidence Dyrk2 KO mice, RNA-seq, immunofluorescence for cilia and Hh components

    PMID:32758357

    Open questions at the time
    • Direct ciliary substrate not yet identified in this study
    • Mechanism linking DYRK2 to Aurka downregulation unclear
  15. 2021 High

    Revealed a mutual DYRK2-CDC25A feedback loop, with DYRK2 driving CDC25A degradation independent of known E3s while CDC25A modulates DYRK2 localization and activity, integrating cell cycle and DDR.

    Evidence Co-IP, phospho-site mapping, in vitro kinase assay, siRNA, phosphoproteomics, cell-cycle analysis

    PMID:34363019

    Open questions at the time
    • E3 ligase mediating CDC25A degradation downstream of DYRK2 unidentified
    • Net directionality of feedback under different conditions unclear
  16. 2021 Medium

    Linked DYRK2 to lung organogenesis through Shh, showing Dyrk2 loss disrupts the Foxf1 gradient and that restoring Shh rescues Foxf1 target expression.

    Evidence Dyrk2 conditional KO mice, RNA-seq, ex vivo lung culture, in situ hybridization, IF

    PMID:34671097

    Open questions at the time
    • Direct ciliary substrate not defined in this study
    • Cell-type specificity of Shh defect not fully resolved
  17. 2022 Medium

    Connected DYRK2 to neddylation and genome stability, showing it complexes with NAE1 and stabilizes it, with DYRK2 loss causing persistent DSBs.

    Evidence Co-IP, neddylation assay, γ-H2AX DSB analysis, KO cells, ubiquitination assay

    PMID:35582972

    Open questions at the time
    • Whether DYRK2 phosphorylates NAE1 directly unclear
    • Single lab without orthogonal in vivo validation
  18. 2022 High

    Used a structure-guided selective inhibitor and phosphoproteomics to identify 4E-BP1 and STIM1 as DYRK2 substrates, linking DYRK2 to protein synthesis and store-operated calcium entry.

    Evidence Co-crystal structure-guided inhibitor (C17), quantitative phosphoproteomics, in vitro kinase assay, STIM1-ORAI1 Co-IP, calcium assay

    PMID:35439114

    Open questions at the time
    • Physiological contexts requiring these substrates not defined
    • Whether 4E-BP1/STIM1 phosphorylation triggers degradation or activity change varies and is incompletely resolved
  19. 2022 Medium

    Showed HIV-1 Vpr hijacks the EDD-DYRK2-DDB1 complex via DCAF1 to enhance CP110 degradation, driving centriole elongation, illustrating viral subversion of DYRK2-EDVP biology.

    Evidence Co-IP, ubiquitination assay, centriole/centrosome imaging, γ-tubulin assay, HIV-1 infection of T cells

    PMID:29724823

    Open questions at the time
    • Consequence for viral replication/pathogenesis not established
    • Whether Vpr alters DYRK2 kinase activity unclear
  20. 2024 High

    Defined the direct ciliary mechanism of Hedgehog activation, showing DYRK2 phosphorylates GLI2/GLI3 at conserved serines at the ciliary base to dissociate them from SUFU and promote nuclear translocation.

    Evidence Dyrk2 KO mice, in vitro kinase assay with site ID, interactome, GLI-SUFU Co-IP, transcriptome, IF

    PMID:38968120

    Open questions at the time
    • How Smoothened activation triggers DYRK2 ciliary activity unclear
    • Crosstalk with other GLI-regulating kinases not resolved
  21. 2025 Medium

    Identified a USP28-DYRK2 reciprocal feedback loop, where DYRK2 promotes USP28 degradation while USP28 deubiquitinates and stabilizes DYRK2 (via T525), tuning the p53-Ser46 apoptotic response.

    Evidence Co-IP, ubiquitination/deubiquitinase assays, kinase-dead and T525 mutants, p53-Ser46 phospho-Western

    PMID:40858801

    Open questions at the time
    • In vivo relevance of the loop not tested
    • Single lab without independent confirmation
  22. 2025 Low

    Provided human genetic evidence that DYRK2's EDVP scaffold function, separable from catalysis, is required for ciliogenesis relevant to kidney development, via CAKUT-associated variants.

    Evidence Co-IP of variant proteins, kinase activity assay, Shh signaling in RPE-1 cells, trio exome sequencing (preprint)

    PMID:40777246

    Open questions at the time
    • Preprint, single lab with limited functional follow-up
    • Causality of variants for CAKUT not formally established
    • No animal modeling of the variants
  23. 2026 Medium

    Linked DYRK2 to renal fibrosis, showing it phosphorylates CDK1 at inhibitory Thr14 to cause G2/M arrest in tubular epithelial cells, with silencing attenuating fibrosis.

    Evidence LC-MS/MS interactomics, Co-IP, CDK1-Thr14 phospho-Western, siRNA, RNA-seq, in vivo fibrosis models

    PMID:41933287

    Open questions at the time
    • Whether DYRK2 phosphorylates CDK1 directly vs via Wee1/Myt1 unclear
    • Single lab; therapeutic translatability untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DYRK2's many activating and inhibitory inputs (ATM, SIAH2, USP28, CDC25A, p38) are integrated to select among its competing substrate programs and subcellular pools in a given context remains unresolved.
  • No unified model of context-specific substrate selection
  • Spatial regulation between nucleus, cytoplasm, and cilium incompletely mapped
  • Whether scaffold vs kinase functions are co-regulated unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 6 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005929 cilium 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 2 R-HSA-168256 Immune System 1 R-HSA-5357801 Programmed Cell Death 1
Partners
DDB1EDDMDM2NAE1RNF8SIAH2USP28VPRBP
Complex memberships
EDD-DDB1-VPRBP (EDVP) E3 ubiquitin ligase complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 DYRK2 directly phosphorylates p53 at Ser46 in the nucleus upon genotoxic stress, inducing p53AIP1 expression and apoptotic cell death in a Ser46 phosphorylation-dependent manner. DYRK2 translocates from cytoplasm to nucleus upon DNA damage to execute this phosphorylation. In vitro kinase assay, phospho-specific antibody detection, siRNA knockdown, nuclear translocation by fractionation/immunofluorescence, apoptosis assays Molecular cell High 17349958
2009 DYRK2 serves as a scaffold for an E3 ubiquitin ligase complex containing EDD, DDB1, and VPRBP (EDVP complex). siRNA depletion of DYRK2 disrupts formation of the EDD-DDB1-VPRBP complex. DYRK2 kinase activity, while dispensable for scaffold function, is required for phosphorylation and subsequent ubiquitin-mediated degradation of the substrate katanin p60. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, kinase-dead mutant analysis Nature cell biology High 19287380
2009 ATM phosphorylates DYRK2 at Thr-33 and Ser-369 upon genotoxic stress, enabling DYRK2 to dissociate from MDM2 and escape proteasomal degradation. Under basal conditions, nuclear DYRK2 is ubiquitinated by MDM2 and constitutively degraded. A functional nuclear localization signal was identified at the N-terminal domain of DYRK2. Co-immunoprecipitation, proteasome inhibitor treatment, phospho-site mutagenesis, siRNA knockdown, subcellular fractionation The Journal of biological chemistry High 19965871
2012 DYRK2 functions as a priming kinase for c-Jun and c-Myc, phosphorylating them to enable subsequent GSK3β phosphorylation and βTrCP-mediated ubiquitin degradation. Knockdown of DYRK2 stabilizes unphosphorylated c-Jun and c-Myc, shortens G1 phase, and accelerates cell proliferation. Co-depletion of c-Jun or c-Myc completely reverses the pro-proliferative effect of DYRK2 knockdown. siRNA knockdown, phospho-specific Western blot, cell cycle analysis, in vivo xenograft, epistasis by co-knockdown The Journal of clinical investigation High 22307329
2012 SIAH2 E3 ligase interacts with DYRK2 and promotes its polyubiquitination and proteasomal degradation. Conversely, DYRK2 phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119), modulating SIAH2 subcellular localization and its ability to degrade PHD3 and stabilize HIF-1α. Under hypoxia, SIAH2-dependent DYRK2 degradation impairs DYRK2-mediated Ser46 phosphorylation of p53. Co-immunoprecipitation, in vitro kinase assay, phosphomimetic/phospho-mutant constructs, ubiquitination assay, subcellular fractionation, siRNA knockdown Journal of molecular cell biology High 22878263
2013 DYRK2 controls EMT in breast cancer by phosphorylating Snail, priming it for GSK3β phosphorylation and subsequent βTrCP-mediated ubiquitin degradation. Knockdown of DYRK2 stabilizes Snail, promotes EMT, and increases cancer invasion in vitro and in vivo. siRNA knockdown, Western blot for Snail stability, invasion assays, in vivo xenograft Cancer letters Medium 23791882
2013 DYRK2 phosphorylates TERT (the catalytic subunit of telomerase), leading to its association with the EDD-DDB1-VprBP E3 ligase complex, ubiquitination, and proteasomal degradation. This regulation occurs specifically at the G2/M phase. Endogenous DYRK2 depletion results in constitutive telomerase activation. Co-immunoprecipitation, in vitro kinase assay, cell cycle synchronization, ubiquitination assay, siRNA knockdown, telomerase activity assay The Journal of biological chemistry High 23362280
2014 DYRK2 phosphorylates hPXR (human pregnane X receptor), and this phosphorylation facilitates subsequent ubiquitination of hPXR by the E3 ligase UBR5, leading to hPXR proteasomal degradation. DYRK2 knockdown phenocopies UBR5 knockdown, resulting in hPXR accumulation and increased hPXR transcriptional activity. Kinome-wide siRNA screen, MS analysis, co-immunoprecipitation, ubiquitination assay, knockdown rescue The Biochemical journal Medium 24438055
2015 DYRK2 negatively regulates virus-triggered type I interferon induction by phosphorylating TBK1 at Ser527, which primes TBK1 for recruitment of NLRP4 and the E3 ubiquitin ligase DTX4, leading to K48-linked ubiquitination and degradation of TBK1. This function is dependent on DYRK2 kinase activity. Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, ubiquitination assay, siRNA knockdown, viral infection assay PLoS pathogens High 26407194
2017 Centrosomal protein Cep78 directly interacts with VprBP, specifically binding EDD-DYRK2-DDB1VprBP but not CRL4VprBP, and inhibits its E3 ligase activity. EDD-DYRK2-DDB1VprBP ubiquitinates CP110 (a novel centrosomal substrate) after DYRK2-mediated phosphorylation of CP110. Cep78 inhibits the final ubiquitin transfer step from EDD to CP110 without affecting CP110 phosphorylation or VprBP binding. Deregulation of this complex perturbs centriole length and cilia assembly. Co-immunoprecipitation, ubiquitination assay, in vitro kinase assay, RNAi knockdown, centrosome/cilia imaging EMBO reports High 28242748
2017 DYRK2 directly interacts with RNF8, and this interaction is required for DNA damage-induced monoubiquitination of γ-H2AX. DYRK2 depletion impairs γ-H2AX ubiquitination, suppresses 53BP1 foci formation at DSBs, and reduces homologous recombination efficiency. High-throughput screening, co-immunoprecipitation, siRNA knockdown, γ-H2AX ubiquitination assay, homologous recombination reporter assay, foci imaging FEBS letters Medium 28194753
2019 p38 MAPK directly phosphorylates Snail at Ser107, which suppresses DYRK2-mediated phosphorylation of Snail at Ser104. DYRK2 phosphorylation of Snail at Ser104 is critical for subsequent GSK3β-dependent phosphorylation and βTrCP-mediated ubiquitination and degradation of Snail. In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis Cancer research High 31209060
2019 KLF4 transcriptionally represses the DYRK2 gene in CML leukemia stem/progenitor cells. Loss of KLF4 elevates DYRK2, which in turn depletes c-Myc protein and activates p53, impairing survival and self-renewal. Stabilization of DYRK2 protein by inhibiting SIAH2 with vitamin K3 promotes apoptosis and abrogates self-renewal in CML stem/progenitor cells. Klf4 conditional knockout mouse model, DYRK2 expression analysis, p53/c-Myc protein quantification, small-molecule SIAH2 inhibitor, colony/sphere-forming assays Blood Medium 31515251
2020 DYRK2 phosphorylates HSF1, promoting its nuclear stability and transcriptional activity in triple-negative breast cancer cells. DYRK2 depletion reduces HSF1 activity and sensitizes TNBC cells to proteotoxic stress. siRNA knockdown, phospho-specific Western blot, HSF1 transcriptional activity assays, proteotoxic stress sensitivity assays Cell death and differentiation Medium 33268814
2020 Loss of Dyrk2 in mice causes suppression of Hedgehog (Hh) signaling, skeletal abnormalities, abnormal ciliary morphology, and defective trafficking of Hh pathway components. Transcriptome analysis revealed downregulation of Aurora kinase A (Aurka) and other cilia disassembly genes following Dyrk2 deletion, identifying DYRK2 as a ciliogenesis-related kinase necessary for Hh signaling during embryogenesis. Dyrk2 knockout mice, in vivo phenotype analysis, RNA-seq, immunofluorescence for cilia morphology and Hh component localization eLife High 32758357
2021 DYRK2 phosphorylates CDC25A on at least 7 residues, leading to its proteasomal degradation independent of known CDC25A E3 ubiquitin ligases. In turn, CDC25A controls DYRK2 phosphorylation at residues outside its activation loop, affecting DYRK2 localization and activity. This mutual regulatory feedback loop influences cell cycle progression and the DNA damage response. Co-immunoprecipitation, phospho-site mapping, in vitro kinase assay, siRNA knockdown, phosphoproteomic analysis, cell cycle analysis Cell death and differentiation High 34363019
2021 Dyrk2-deficient mice display congenital malformations including lung hypoplasia, with disrupted Foxf1 expression gradient in lung mesenchyme and reduced Foxf1 target genes necessary for proper airway and alveolar development. Restoring Shh signaling in ex vivo Dyrk2-deficient lung culture rescues Foxf1 and target gene expression. Dyrk2 conditional knockout mice, RNA-seq, ex vivo lung culture, in situ hybridization, immunofluorescence Communications biology Medium 34671097
2022 DYRK2 promotes neddylation of cullins by forming a complex with NAE1 (a component of NEDD8-activating enzyme E1) and maintaining NAE1 protein level by suppressing its polyubiquitylation. Deletion of DYRK2 leads to persistent DNA double-strand breaks and genome instability. Co-immunoprecipitation, neddylation assay, DSB analysis (γ-H2AX), DYRK2 knockout cells, ubiquitination assay Journal of cell science Medium 35582972
2022 Using a potent selective DYRK2 inhibitor (C17) and quantitative phosphoproteomics, 4E-BP1 and STIM1 were identified as novel DYRK2 substrates. DYRK2 phosphorylates 4E-BP1 at multiple sites to regulate protein synthesis. DYRK2 phosphorylates STIM1, substantially increasing STIM1 interaction with the ORAI1 channel and promoting store-operated calcium entry. Structure-based inhibitor design with co-crystal structures, quantitative phosphoproteomics, in vitro kinase assay, Co-IP (STIM1-ORAI1), calcium entry assay eLife High 35439114
2022 DYRK2 binds Twist and promotes its proteasomal degradation via ubiquitination in colorectal cancer cells, reducing EMT and chemoresistance. Co-immunoprecipitation confirmed direct DYRK2-Twist interaction. Co-immunoprecipitation, ubiquitination assay, Western blot, siRNA knockdown/overexpression, in vivo xenograft Scientific reports Medium 36577753
2013 DYRK2 negatively regulates cardiomyocyte growth by acting as a priming kinase for GSK-3β-mediated phosphorylation of eIF2Bε at Ser535, thereby inhibiting eIF2Bε activity and protein synthesis. DYRK2 overexpression increases phospho-eIF2Bε, reduces cardiomyocyte size, and diminishes hypertrophic response to adrenergic stimulation. Transgenic mouse overexpression, adenoviral overexpression, siRNA knockdown in cardiomyocytes, phospho-specific Western blot, isoproterenol stimulation, aortic banding model PloS one Medium 24023715
2024 DYRK2 acts as a ciliary kinase that positively regulates Hedgehog signaling by phosphorylating GLI2 and GLI3 on evolutionarily conserved serine residues at the ciliary base downstream of Smoothened activation. This phosphorylation induces dissociation of GLI2/GLI3 from the suppressor SUFU and their nuclear translocation. Loss of Dyrk2 in mice causes skeletal malformation, and DYRK2-mediated phosphorylation controls limb cell proliferation. Dyrk2 knockout mice, in vitro kinase assay with phospho-site identification, interactome analysis, Co-IP (GLI-SUFU), transcriptome analysis, immunofluorescence for ciliary localization and nuclear translocation Proceedings of the National Academy of Sciences of the United States of America High 38968120
2025 DYRK2 phosphorylates USP28, promoting its ubiquitination and proteasomal degradation in a kinase activity-independent manner. Conversely, USP28 deubiquitinates DYRK2, stabilizing its protein levels and enhancing its kinase activity. The 521–541 region of DYRK2, particularly residue T525, is required for USP28-mediated DYRK2 stabilization. This feedback loop modulates p53 Ser46 phosphorylation and apoptotic responses to DNA damage. Co-immunoprecipitation, ubiquitination assay, kinase-dead mutant analysis, site-directed mutagenesis (T525), deubiquitinase assay, p53-Ser46 phospho-specific Western blot Cell death and differentiation Medium 40858801
2018 HIV-1 Vpr localizes to the centrosome through DCAF1 binding and forms a complex with EDD-DYRK2-DDB1DCAF1, enhancing ubiquitination and degradation of CP110 (an EDD-DYRK2-DDB1 substrate), leading to centriole elongation and increased microtubule nucleation. Cep78 expression overcomes the Vpr-mediated CP110 degradation. Co-immunoprecipitation, ubiquitination assay, immunofluorescence for centrosome/centriole length, γ-tubulin recruitment assay, HIV-1 infection of T lymphocytes The Journal of biological chemistry Medium 29724823
2016 Diminished DYRK2 leads to mTOR stabilization by reducing Thr631 phosphorylation of mTOR, which is required for mTOR ubiquitination and degradation. Ectopic DYRK2 expression promotes mTOR phosphorylation at Thr631 and its subsequent degradation, activating the mTORC1 pathway when DYRK2 is depleted. Ectopic DYRK2 overexpression, phospho-specific Western blot (mTOR Thr631), ubiquitination assay, siRNA knockdown, xenograft model Cancer letters Medium 27746162
2026 DYRK2 interacts with CDK1 (identified by mass spectrometry and co-immunoprecipitation) and promotes inhibitory phosphorylation of CDK1 at Thr14, thereby inhibiting CDK1 activity and causing G2/M phase arrest in renal tubular epithelial cells under fibrotic conditions. Silencing DYRK2 restores CDK1 activity and cell cycle progression, and attenuates renal fibrosis. LC–MS/MS interactomics, co-immunoprecipitation, phospho-specific Western blot (CDK1 Thr14), siRNA knockdown, RNA-seq, in vivo fibrosis mouse models Cellular & molecular biology letters Medium 41933287
2025 Two DYRK2 variants identified in CAKUT patients disrupted EDD-DYRK2-DDB1VprBP complex formation without affecting DYRK2 kinase activity, establishing that DYRK2's scaffold function in the EDVP complex is genetically separable from its catalytic activity and is required for proper ciliogenesis relevant to kidney development. Co-immunoprecipitation of variant proteins, kinase activity assay, Shh signaling in RPE-1 cells, trio exome sequencing bioRxivpreprint Low 40777246
2012 In zebrafish, DYRK2 phosphorylates CRMP2 (Dpysl2) and CRMP4 (Dpysl3), and this phosphorylation is required (together with Cdk5) for proper positioning of Rohon-Beard sensory neurons and neural crest cells during neurulation. Phosphorylation-mimicking forms of Dpysl2/Dpysl3 rescue the ectopic cell positioning phenotype seen in cdk5/dyrk2 double morphants. Morpholino knockdown in zebrafish, cell transplantation, phosphomimetic rescue experiments Developmental biology Medium 22898304
2005 In C. elegans, the DYRK2 ortholog MBK-2 directly phosphorylates OMA-1 at T239, which is required for OMA-1 function in the 1-cell embryo and for its timely degradation after the first mitotic division. Phosphorylation at T239 by MBK-2 facilitates subsequent phosphorylation of OMA-1 by GSK-3 at T339 in vitro, and both phosphorylations are required for correctly-timed OMA-1 degradation in vivo. In vitro kinase assay, phospho-site mutagenesis, RNAi, in vivo developmental analysis Developmental biology High 16289132
2008 In C. elegans, the DYRK2 ortholog MBK-2 primes MEX-5 at T186 for subsequent polo kinase-dependent phosphorylation. Phosphorylation of MEX-5 at T186 by MBK-2 greatly enhances MEX-5 phosphorylation by polo kinases in vitro. T186 phosphorylation is required for polo kinase binding via polo box domains and is essential for MEX-5 function in regulating embryonic polarity. In vitro kinase assay, phospho-site mutagenesis, genetic analysis, polo box domain binding assay Development (Cambridge, England) High 18199581
2016 Reduced DYRK2 expression increases KLF4 expression in breast cancer cells through androgen receptor (AR)-dependent transcriptional regulation of the KLF4 promoter, which depends on DYRK2 kinase activity. Elevated KLF4 then induces cancer stem-like properties. siRNA knockdown, KLF4 promoter luciferase assay, AR chromatin immunoprecipitation, kinase-dead mutant, sphere-forming assays, xenograft Oncogene Medium 27721402
2024 DYRK2 promotes ubiquitination and degradation of Twist1 in breast cancer cells by phosphorylating Twist1 (decreased Twist1 phosphorylation and increased ubiquitination observed after DYRK2 overexpression). Twist1 degradation reduces GSTP1 promoter binding by Twist1, suppressing GSTP1 transcription and reversing chemoresistance to docetaxel. Western blot, ubiquitination assay, lentiviral DYRK2 overexpression, phospho-specific western blot, promoter binding analysis, in vivo xenograft Journal of molecular histology Low 39641870

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Molecular cell 239 17349958
2009 Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase. Nature cell biology 161 19287380
2012 DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells. The Journal of clinical investigation 118 22307329
2008 Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6. Development (Cambridge, England) 89 18199581
2005 DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1, a key regulator of the oocyte-to-embryo transition in C. elegans. Developmental biology 80 16289132
2013 DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail. Cancer letters 67 23791882
2013 Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation. The Journal of biological chemistry 61 23362280
2009 ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage. The Journal of biological chemistry 61 19965871
2015 DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation. PLoS pathogens 58 26407194
2012 Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways. Journal of molecular cell biology 51 22878263
2003 Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas. Cancer research 50 12874018
2017 Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP. EMBO reports 48 28242748
2021 Emerging roles of DYRK2 in cancer. The Journal of biological chemistry 47 33376136
2019 p38 Stabilizes Snail by Suppressing DYRK2-Mediated Phosphorylation That Is Required for GSK3β-βTrCP-Induced Snail Degradation. Cancer research 44 31209060
2019 Multiple functions of DYRK2 in cancer and tissue development. FEBS letters 42 31505048
2017 Decrease of miR-622 expression suppresses migration and invasion by targeting regulation of DYRK2 in colorectal cancer cells. OncoTargets and therapy 42 28260923
2020 Updating dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2): molecular basis, functions and role in diseases. Cellular and molecular life sciences : CMLS 40 32462403
2019 A KLF4-DYRK2-mediated pathway regulating self-renewal in CML stem cells. Blood 39 31515251
2015 Engagement of DYRK2 in proper control for cell division. Cell cycle (Georgetown, Tex.) 38 25603354
2010 Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorganic & medicinal chemistry letters 38 20836251
2012 Dpysl2 (CRMP2) and Dpysl3 (CRMP4) phosphorylation by Cdk5 and DYRK2 is required for proper positioning of Rohon-Beard neurons and neural crest cells during neurulation in zebrafish. Developmental biology 36 22898304
2014 Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and serine/threonine kinase DYRK2. The Biochemical journal 35 24438055
2020 The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis. eLife 32 32758357
2020 The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress. Cell death and differentiation 32 33268814
2015 DYRK2 regulates epithelial-mesenchymal-transition and chemosensitivity through Snail degradation in ovarian serous adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 25712377
2021 A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival. Cell death and differentiation 31 34363019
2016 Impairment of DYRK2 augments stem-like traits by promoting KLF4 expression in breast cancer. Oncogene 31 27721402
2009 DYRK2 expression may be a predictive marker for chemotherapy in non-small cell lung cancer. Anticancer research 31 19596956
2019 Forced expression of DYRK2 exerts anti-tumor effects via apoptotic induction in liver cancer. Cancer letters 29 30851422
2017 Dyrk2 mediated the release of proinflammatory cytokines in LPS-induced BV2 cells. International journal of biological macromolecules 23 29155197
2018 HIV-1 Vpr hijacks EDD-DYRK2-DDB1DCAF1 to disrupt centrosome homeostasis. The Journal of biological chemistry 22 29724823
2014 Downregulation of DYRK2 can be a predictor of recurrence in early stage breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 25095982
2016 Diminished DYRK2 sensitizes hormone receptor-positive breast cancer to everolimus by the escape from degrading mTOR. Cancer letters 19 27746162
2015 Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) as a novel marker in T1 high-grade and T2 bladder cancer patients receiving neoadjuvant chemotherapy. BMC urology 19 26087959
2022 Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry. eLife 17 35439114
2020 Impairment of DYRK2 by DNMT1‑mediated transcription augments carcinogenesis in human colorectal cancer. International journal of oncology 17 32236621
2017 Interaction between RNF8 and DYRK2 is required for the recruitment of DNA repair molecules to DNA double-strand breaks. FEBS letters 17 28194753
2013 DYRK2 negatively regulates cardiomyocyte growth by mediating repressor function of GSK-3β on eIF2Bε. PloS one 17 24023715
2024 Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase. Proceedings of the National Academy of Sciences of the United States of America 15 38968120
2023 Dual inhibition of HSF1 and DYRK2 impedes cancer progression. Bioscience reports 14 36622366
2015 Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma. International journal of biological macromolecules 14 26341817
2021 Mice lacking DYRK2 exhibit congenital malformations with lung hypoplasia and altered Foxf1 expression gradient. Communications biology 13 34671097
2017 Regulation of Glioma Cells Migration by DYRK2. Neurochemical research 13 28677030
2013 Drosophila Dyrk2 plays a role in the development of the visual system. PloS one 13 24146926
2023 Discovery of Potent DYRK2 Inhibitors with High Selectivity, Great Solubility, and Excellent Safety Properties for the Treatment of Prostate Cancer. Journal of medicinal chemistry 12 36800260
2017 Dyrk2 involved in regulating LPS-induced neuronal apoptosis. International journal of biological macromolecules 12 28676338
2017 DYRK2 displays muscle fiber type specific function during zebrafish early somitogenesis. The International journal of developmental biology 10 28695966
2023 Dyrk2 gene transfer suppresses hepatocarcinogenesis by promoting the degradation of Myc and Hras. JHEP reports : innovation in hepatology 9 37333975
2023 DYRK2 promotes chemosensitivity via p53-mediated apoptosis after DNA damage in colorectal cancer. Cancer science 9 37776195
2023 Anti-Proliferative Potential of Cynaroside and Orientin-In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies. International journal of molecular sciences 9 38068880
2022 DYRK2 downregulation in colorectal cancer leads to epithelial-mesenchymal transition induction and chemoresistance. Scientific reports 8 36577753
2022 DYRK2 maintains genome stability via neddylation of cullins in response to DNA damage. Journal of cell science 7 35582972
2025 Curcuminoids WM03 inhibits ovarian cancer cisplatin-resistant cells proliferation and reverses cisplatin resistance by targeting DYRK2. Phytomedicine : international journal of phytotherapy and phytopharmacology 6 40315643
2024 Discovery of a dual-target DYRK2 and HDAC8 inhibitor for the treatment of hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 6 38889633
2023 Discovery of Potent, Selective, and Orally Bioavailable DYRK2 Inhibitors for the Treatment of Prostate Cancer. Journal of medicinal chemistry 6 38033250
2022 Grass carp (Ctenopharyngodon idella) DYRK2 modulates cell apoptosis through phosphorylating p53. Fish & shellfish immunology 6 35781054
2022 A pan-cancer analysis of the oncogenic role of dual-specificity tyrosine (Y)-phosphorylation- regulated kinase 2 (DYRK2) in human tumors. Scientific reports 6 36104345
2020 DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells. Experimental & molecular medicine 6 33067577
2023 Functional Roles of DYRK2 as a Tumor Regulator. Current issues in molecular biology 5 37886981
2020 Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma. Histology and histopathology 5 33368138
2024 CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis. Molecular biology reports 4 38727863
2022 Combination of DYRK2 and TERT Expression Is a Powerful Predictive Marker for Early-stage Breast Cancer Recurrence. Anticancer research 4 35347031
2020 Determination of genetic variation within the DYRK2 gene and its associations with milk traits in cattle. Archives animal breeding 4 32964102
2024 The diverse functions of DYRK2 in response to cellular stress. Histology and histopathology 3 38656683
2025 Identification of DYRK2 and TRIM32 as keloids programmed cell death-related biomarkers: insights from bioinformatics and machine learning in multiple cohorts. Computer methods in biomechanics and biomedical engineering 2 40127455
2025 Benzamide Derivatives of Thioacridine as DYRK2 and DYRK3 Dual Inhibitors. ChemMedChem 2 40145237
2025 A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling. Cell death and differentiation 2 40858801
2024 Discovery of the First Potent DYRK2 Proteolysis Targeting Chimera Degraders. ACS medicinal chemistry letters 2 38746900
2024 DYRK2 regulates epithelial-mesenchymal transition restriction in pancreatic cancer liver metastasis by inhibiting Twist. Digestion 2 39561721
2024 DYRK2 controls GSTPI expression through ubiquitination and degradation of Twist1 to reduce chemotherapy resistance caused by EMT in breast cancer. Journal of molecular histology 2 39641870
2026 The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis. Cancer metastasis reviews 1 41524942
2026 A physics-informed graph neural network to approximate docking-based binding affinity for DYRK2 in Alzheimer's drug repurposing. Scientific reports 1 41673049
2025 CAKUT variants in PRPF8, DYRK2, and CEP78: implications for splicing and ciliogenesis. bioRxiv : the preprint server for biology 1 40777246
2026 DYRK2 drives renal fibrosis through CDK1-dependent G2/M phase dysregulation in tubular epithelial cells. Cellular & molecular biology letters 0 41933287
2015 [Effect of Danshen-containing serum on expression of SuFu and DYRK2 in HSCs]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 0 27097426

Missed literature

Know a paper Affinage missed for DYRK2? Flag it for the maintainers and the community.

No submissions yet.