DYRK1A is a dual-specificity protein kinase with nuclear, cytoplasmic and cytoskeleton-associated pools. It phosphorylates serine/threonine-containing substrates and undergoes tyrosine autophosphorylation. Its substrate repertoire includes the RNA polymerase II C-terminal domain, histone H3, Tau and splicing factors, connecting kinase activity to transcription, chromatin regulation, alternative splicing and neuronal function. The histidine-rich C-terminal region contributes to RNA polymerase II targeting. Natural products share the kinase domain but differ in their terminal sequences; the shorter products lack this histidine-rich region. Human pathogenic variants cause an autosomal dominant neurodevelopmental disorder commonly including microcephaly and intellectual disability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A regulates alternative exon choice through splicing-factor phosphorylation. Reason: The rat Q63470 donor has actual splicing-factor association and phosphorylation evidence. PMID21215488 and PMID22767602 use rat DYRK1A reagents in several cell backgrounds and measure Tau exon-10 inclusion/exclusion. Their effects depend on the splicing factor and cell context, matching regulation of alternative splicing rather than a universal increase in RNA-splicing rate. The conserved activity is retained without relabeling a rodent construct as human. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0003713 transcription coactivator activity | IBA GO_REF:0000033 | ACCEPT | Summary: A conserved transcription-coactivator role complements DYRK1A kinase activity. Reason: The literal IBD at PTN000624548 supports this term, and the exact human target descends from that node in the 1,390-sequence tree/MSA. Human DYRK1B/Q9Y463 donor PMID11980910 reports HNF1/DCoH-dependent coactivation; target studies establish kinase-dependent promoter-associated transcription and histone effects. This is a conserved coregulator inference, not a claim that DYRK1A binds DNA sequence motifs directly; the latter was not detected in PMID25620562. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000624548 SUPPORTS TRANSFER Literal IBD and target descent were reconstructed in PTHR24058; full target sequence matches. Source-side donor experiments and target evidence are distinguished in the reason. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad kinase assertion to the demonstrated dual-specificity activity. Reason: The InterPro IPR008271 mapping correctly identifies the protein-kinase family but stops at the broad parent. Purified human DYRK1A experiments establish serine/threonine phosphorylation and tyrosine autophosphorylation, including weak tyrosine activity after maturation. Current GO:0004712 is a typed descendant of GO:0004672 and describes these activities without requiring all substrates to share a strict proline-directed motif. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR008271 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. Proposed replacements: protein serine/threonine/tyrosine kinase activity Supporting Evidence: GO_REF:0000002 PMID:23665168 DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity. |
| GO:0004672 protein kinase activity | TAS PMID:8769099 Cloning of a human homolog of the Drosophila minibrain/rat D... | MODIFY | Summary: Refine the broad kinase assertion to the demonstrated dual-specificity activity. Reason: The historical human minibrain cloning study supports kinase-family membership; it does not by itself resolve every substrate class. Purified human DYRK1A experiments establish serine/threonine phosphorylation and tyrosine autophosphorylation, including weak tyrosine activity after maturation. Current GO:0004712 is a typed descendant of GO:0004672 and describes these activities without requiring all substrates to share a strict proline-directed motif. Proposed replacements: protein serine/threonine/tyrosine kinase activity |
| GO:0004672 protein kinase activity | TAS PMID:8975710 Isolation of human and murine homologues of the Drosophila m... | MODIFY | Summary: Refine the broad kinase assertion to the demonstrated dual-specificity activity. Reason: The historical human cloning and mapping study supplies the original kinase context, with finer biochemical specificity established subsequently. Purified human DYRK1A experiments establish serine/threonine phosphorylation and tyrosine autophosphorylation, including weak tyrosine activity after maturation. Current GO:0004712 is a typed descendant of GO:0004672 and describes these activities without requiring all substrates to share a strict proline-directed motif. Proposed replacements: protein serine/threonine/tyrosine kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: The exact target sequence descends from the experimentally grounded PTN000624408 IBD in PTHR24058. The broad descendant evidence includes the target itself legitimately; neither donor count nor self-inclusion is a propagation defect. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000624408 SUPPORTS TRANSFER Literal IBD and target descent were reconstructed in PTHR24058; full target sequence matches. Source-side donor experiments and target evidence are distinguished in the reason. |
| GO:0004674 protein serine/threonine kinase activity | IGI PMID:17906291 DYRK1A-mediated hyperphosphorylation of Tau. A functional li... | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: The imported mouse Q61214 interaction/genetic context in PMID17906291 concerns DYRK1A-dependent Tau phosphorylation. The normal cache is abstract-only, so its exact constructs are not reconstructed; independent human biochemistry confirms the same catalytic activity. |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: Current mouse Q61214 source annotations include direct serine/threonine-kinase experiments. The source is a mammalian ortholog, and human recombinant activity independently corroborates the transferred function. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: Rat Q63470 is the experimentally studied Dyrk1a ortholog. Donor PMID8631952 reports recombinant kinase activity, and independently assayed human enzyme supports the same chemistry. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0004674 protein serine/threonine kinase activity | ISS PMID:20736167 Direct association of Sprouty-related protein with an EVH1 d... | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: PMID20736167 uses mouse-brain-derived DYRK1A and Tau constructs in phosphorylation and SPRED-regulation assays. Host human cells do not make those constructs human; the conserved catalytic function is independently supported in human protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0004674 protein serine/threonine kinase activity | NAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: The cited Tau-kinase review explicitly discusses DYRK1A substrate phosphorylation. Its summary is corroborated by direct human recombinant DYRK1A/Tau and other substrate assays. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:8769099 Cloning of a human homolog of the Drosophila minibrain/rat D... | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: The historical human minibrain study identifies the kinase and its developmental context. Later direct human substrate assays establish the same serine/threonine activity. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-1362270 | ACCEPT | Summary: DYRK1A catalyzes protein serine/threonine phosphorylation. Reason: The current Reactome reaction1362270 has catalyst1362272, GO:0004674, linked to human DYRK1A entity1362267/Q13627 residues1-763 in nucleoplasm. It phosphorylates LIN52 within MuvB; this is an explicit catalytic role rather than mere pathway membership. Supporting Evidence: Reactome:R-HSA-1362270 |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined enzyme/domain mapping correctly captures DYRK1A dual specificity. Reason: The imported EC2.7.12.1 and IPR044131 sources agree with directly measured human serine/threonine activity and tyrosine autophosphorylation. The generic dual-specificity term does not imply equal rates for these reactions or activity of every natural splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR044131 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. EC:2.7.12.1 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:20981014 Development of a novel selective inhibitor of the Down syndr... | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: The authentic PMID20981014 abstract describes ATP-pocket inhibition and DYRK1A activity, but the complete target-specific assay was not recovered. Its curated experimental assertion is retained because independent human biochemical evidence confirms tyrosine autophosphorylation. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:22998443 Selectivity, cocrystal structures, and neuroprotective prope... | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: The authentic PMID22998443 abstract describes DYRK-family inhibitor and structural assays. The original target-specific Tyr readout was not recovered, so it is not reconstructed here; independent human biochemical evidence supports the function. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:23665168 Structures of Down syndrome kinases, DYRKs, reveal mechanism... | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: The independently read human recombinant study measures tyrosine autophosphorylation and weak tyrosine activity of mature enzyme as well as its predominant serine/threonine activity. This is not limited by an assumed absolute maturation-only rule. Supporting Evidence: |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:24239188 Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a... | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: The PMID24239188 title and abstract emphasize DYRK1B, but that does not show that the full study omitted DYRK1A. The imported experimental assertion is retained with explicit access limits and independent direct human DYRK1A support. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: The imported RHEA10596 source denotes ATP-dependent phosphorylation of a protein tyrosine. Official DYRK1A catalytic annotation and direct human biochemical assays support this reaction, including autophosphorylation. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:10596 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0004713 protein tyrosine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Tyrosine phosphorylation is a real component of DYRK1A catalytic activity. Reason: Rat Q63470 has direct experimental tyrosine-kinase/autophosphorylation grounding. The conserved activity is corroborated in human recombinant enzyme; the transfer does not require identical activity levels in every assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:9748265 Sequence characteristics, subcellular localization, and subs... | ACCEPT | Summary: DYRK1A is a non-membrane-spanning tyrosine-active protein kinase. Reason: Current GO:0004715 requires the non-membrane-spanning enzyme to phosphorylate protein tyrosine; it is not restricted to a different kinase lineage. PMID9748265 describes family characterization and recombinant DYRK1A autophosphorylation with rodent construct context. Human biochemical evidence independently confirms the activity, without reassigning the historical reagent species. |
| GO:0005515 protein binding | IPI PMID:14500717 Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epith... | MODIFY | Summary: Refine the RANBP9 association to its supported partner class. Reason: The original abstract explicitly reports inhibition of DYRK1A as well as DYRK1B by RanBPM. The full target-specific binding assay was unavailable; retain the curator-assigned DYRK1AβRANBP9 pair rather than infer a paralog miscitation from the title. The official RANBP9 record describes receptor-to-signaling adaptor/scaffold functions and DYRK inhibition. The refinement names the scaffold partner class; it does not assert that DYRK1A itself scaffolds the complex. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:14593110 Phosphorylation of Ser640 in muscle glycogen synthase by DYR... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The authentic abstract reports rabbit-muscle DYRK1A/HAN11 purification and coexpression coimmunoprecipitation in COS cells. Exact expression-construct species was not reconstructed; the DYRK1AβDCAF7 relationship is independently corroborated. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:15694837 Dual-specificity tyrosine-phosphorylated and regulated kinas... | KEEP AS NON CORE | Summary: Retain the positive PHYHIP association as non-core. Reason: The authentic abstract reports C-terminal DYRK1A yeast-two-hybrid association with PHYHIP, coimmunoprecipitation after cotransfection, and redistribution in PC12 cells. Host species is not used to authenticate the protein construct. PHYHIP association is positive, but its hydroxylase-associated name does not establish hydroxylase catalysis or another supported informative partner class. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:20736167 Direct association of Sprouty-related protein with an EVH1 d... | KEEP AS NON CORE | Summary: Retain the positive SPRED2 association as non-core. Reason: The recovered original reports endogenous human PC3 DYRK1AβSPRED coimmunoprecipitation, while several functional constructs were cloned from mouse brain. Preserve those distinct experimental scopes. SPRED2 recruits NF1 and regulates Ras signaling; NF1 performs the GTP-hydrolysis step. These functions do not make SPRED2 a Ras GTPase or establish an informative binding class here. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:20736167 Direct association of Sprouty-related protein with an EVH1 d... | KEEP AS NON CORE | Summary: Retain the positive SPRED1 association as non-core. Reason: The recovered original reports endogenous human PC3 DYRK1AβSPRED coimmunoprecipitation, while several functional constructs were cloned from mouse brain. Preserve those distinct experimental scopes. SPRED1 is a signaling regulator and kinase substrate. Its effects on MAPK signaling do not establish kinase or GTPase catalysis by the partner. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:20940704 The WD40-repeat protein Han11 functions as a scaffold protei... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The recovered original reports Han11/DYRK association in cellular and in-vitro-translation experiments and a functional scaffold effect on kinase coupling. In-vitro translation is not a purified-component binary assay. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:20940704 Han11 was required to allow coupling of MEKK1 to DYRK1 and HIPK2. UniProtKB:P61962 |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Refine the RB1 association to its supported partner class. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. Official RB1 functional evidence establishes E2F-associated transcriptional corepression. Current GO:0001221 describes binding to a transcription coregulator; it does not transfer RB1 activity to DYRK1A. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Refine the RBL1 association to its supported partner class. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. Official RBL1/p107 evidence establishes E2F-associated transcriptional corepression. This is the verified partner class, without attributing its transcriptional activity to DYRK1A. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Refine the DYNLL1 association to its supported partner class. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. P63167 is dynein light chain DYNLL1. The narrower term names the partner class, without implying that DYRK1A is a dynein motor or that every measured complex functions in transport. Proposed replacements: dynein light chain binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | KEEP AS NON CORE | Summary: Retain the positive TROAP association as non-core. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. The retrieved official TROAP record provides adhesion-complex context but no sufficiently established narrower molecular partner class for this interaction. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | KEEP AS NON CORE | Summary: Retain the positive LZTS2 association as non-core. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. LZTS2 regulates katanin-mediated microtubule severing and localization. That regulatory role does not itself establish that LZTS2 is a motor, a catalytic severing enzyme, or a structural cytoskeletal component. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | KEEP AS NON CORE | Summary: Retain the positive FAM53C association as non-core. Reason: The indexed original describes tandem-affinity CMGC-kinase interaction mapping in human HEK293 cells and selected coimmunoprecipitation/BiFC validations. The exact imported pair is retained in the IntAct record; not every pair is described as purified direct contact. FAM53C interaction is positive, including targeted follow-up in PMID35914814, but a supported informative molecular partner class was not resolved. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | KEEP AS NON CORE | Summary: Retain the positive TROAP association as non-core. Reason: The original Methods describe replicated affinity/crosslink proteomics in differentiated human SH-SY5Y cells with negative controls and SAINT filtering. The exact targetβpartner record is recovered in MINT; this supports association, not a reconstructed purified interface. The retrieved official TROAP record provides adhesion-complex context but no sufficiently established narrower molecular partner class for this interaction. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | KEEP AS NON CORE | Summary: Retain the positive LZTS2 association as non-core. Reason: The original Methods describe replicated affinity/crosslink proteomics in differentiated human SH-SY5Y cells with negative controls and SAINT filtering. The exact targetβpartner record is recovered in MINT; this supports association, not a reconstructed purified interface. LZTS2 regulates katanin-mediated microtubule severing and localization. That regulatory role does not itself establish that LZTS2 is a motor, a catalytic severing enzyme, or a structural cytoskeletal component. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The human SF-TAP interactome and literal IntAct pair support this association. Construct sequencing and peptide/protein filtering are described in the original; the assay does not uniquely establish a natural splice product. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The authentic abstract establishes human affinity-purification complexome mapping, and the literal IntAct record contains the DYRK1AβDCAF7 pair. Complete target-specific Methods were unavailable; the same association has independent support. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | MODIFY | Summary: Refine the TRAF2 association to its supported partner class. Reason: The actual Virotrap Methods use human ORFeome/Gag constructs in HEK293T cells and control-bait filtering. Two literal IntAct records support the pair; a packaged complex is not necessarily a purified direct interface. Official TRAF2 evidence supports its ubiquitin-protein-ligase class. The binding refinement does not assign ubiquitin transfer or TRAF2 signaling to DYRK1A. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the positive KPRP association as non-core. Reason: The exact HuRI pair appears in three IntAct records. The original describes binary yeast-two-hybrid screening, retesting and sequence confirmation; native cellular function and natural isoform specificity remain separate questions. The verified HuRI pair supports association with KPRP. Its keratinocyte-proline-rich name does not make it a keratin or establish an intermediate-filament binding refinement. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Refine the RB1 association to its supported partner class. Reason: The human tagged-protein affinity map and exact IntAct pair support association. The original Methods describe single-locus expression, extensive GFP controls and interaction scoring, without establishing an isolated binary interface. Official RB1 functional evidence establishes E2F-associated transcriptional corepression. Current GO:0001221 describes binding to a transcription coregulator; it does not transfer RB1 activity to DYRK1A. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Refine the RBL1 association to its supported partner class. Reason: The human tagged-protein affinity map and exact IntAct pair support association. The original Methods describe single-locus expression, extensive GFP controls and interaction scoring, without establishing an isolated binary interface. Official RBL1/p107 evidence establishes E2F-associated transcriptional corepression. This is the verified partner class, without attributing its transcriptional activity to DYRK1A. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The human tagged-protein affinity map and exact IntAct pair support association. The original Methods describe single-locus expression, extensive GFP controls and interaction scoring, without establishing an isolated binary interface. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The exact BioPlex pair is retained in IntAct, with source Methods establishing sequence-checked human ORFeome baits, affinity capture and statistical filtering. These are positive association data rather than purified binary measurements. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the DYNLL1 association to its supported partner class. Reason: The exact BioPlex pair is retained in IntAct, with source Methods establishing sequence-checked human ORFeome baits, affinity capture and statistical filtering. These are positive association data rather than purified binary measurements. P63167 is dynein light chain DYNLL1. The narrower term names the partner class, without implying that DYRK1A is a dynein motor or that every measured complex functions in transport. Proposed replacements: dynein light chain binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the USP54 association to its supported partner class. Reason: The exact BioPlex pair is retained in IntAct, with source Methods establishing sequence-checked human ORFeome baits, affinity capture and statistical filtering. These are positive association data rather than purified binary measurements. The current official USP54 record Q70EL1 supports its deubiquitinase classification through experimentally evidenced FUNCTION and CATALYTIC ACTIVITY statements (ECO:0000269), independently of its name or GO cross-references. This is curated partner-class evidence; the underlying enzymology papers were not independently reread here. GO:1990381 names binding to this enzyme class, without assigning deubiquitination to DYRK1A. Proposed replacements: ubiquitin-specific protease binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the positive LZTS2 association as non-core. Reason: The exact BioPlex pair is retained in IntAct, with source Methods establishing sequence-checked human ORFeome baits, affinity capture and statistical filtering. These are positive association data rather than purified binary measurements. LZTS2 regulates katanin-mediated microtubule severing and localization. That regulatory role does not itself establish that LZTS2 is a motor, a catalytic severing enzyme, or a structural cytoskeletal component. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the positive FAM53C association as non-core. Reason: The exact BioPlex pair is retained in IntAct, with source Methods establishing sequence-checked human ORFeome baits, affinity capture and statistical filtering. These are positive association data rather than purified binary measurements. FAM53C interaction is positive, including targeted follow-up in PMID35914814, but a supported informative molecular partner class was not resolved. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The source is an authenticated transactivator proteomics study, but the target-specific table/assay was not independently recovered and this bounded IntAct/MINT retrieval did not supply its pair. The curator-assigned DYRK1AβDCAF7 association is retained and the gene-level class refinement is independently grounded by other cited experiments. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Refine the DYNLL1 association to its supported partner class. Reason: The original OpenCell row is a DYNLL1-bait capture with a prey accession group containing DYRK1A and DYRK1B variants. It is not a unique DYRK1A peptide/isoform assignment. Independent DYRK1AβDYNLL1 screens support the gene-level binding refinement while this source-specific ambiguity remains explicit. P63167 is dynein light chain DYNLL1. The narrower term names the partner class, without implying that DYRK1A is a dynein motor or that every measured complex functions in transport. Proposed replacements: dynein light chain binding |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | MODIFY | Summary: Refine the DYNLL1 association to its supported partner class. Reason: The genuine Table S3 and literal interaction records establish a positive yeast-two-hybrid pair. The original distinguishes the polyhistidine-deleted DYRK1A bait from wild type; reference-parent sequence checksums do not authenticate an unmodified experimental insert. Table S3 row782 uses DYRK1AΞpolyHis and DYNLL1 nucleotide17β270. P63167 is dynein light chain DYNLL1. The narrower term names the partner class, without implying that DYRK1A is a dynein motor or that every measured complex functions in transport. Proposed replacements: dynein light chain binding |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | MODIFY | Summary: Refine the TRAF2 association to its supported partner class. Reason: The genuine Table S3 and literal interaction records establish a positive yeast-two-hybrid pair. The original distinguishes the polyhistidine-deleted DYRK1A bait from wild type; reference-parent sequence checksums do not authenticate an unmodified experimental insert. Table S3 row824 uses DYRK1AΞpolyHis and TRAF2 nucleotide650β1125. Official TRAF2 evidence supports its ubiquitin-protein-ligase class. The binding refinement does not assign ubiquitin transfer or TRAF2 signaling to DYRK1A. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | MODIFY | Summary: Refine the USP54 association to its supported partner class. Reason: The genuine Table S3 and literal interaction records establish a positive yeast-two-hybrid pair. The original distinguishes the polyhistidine-deleted DYRK1A bait from wild type; reference-parent sequence checksums do not authenticate an unmodified experimental insert. Table S3 rows710/819 use wild-type and ΞpolyHis baits with USP54 nucleotide3863β4233/3863β4170 fragments, respectively. The current official USP54 record Q70EL1 supports its deubiquitinase classification through experimentally evidenced FUNCTION and CATALYTIC ACTIVITY statements (ECO:0000269), independently of its name or GO cross-references. This is curated partner-class evidence; the underlying enzymology papers were not independently reread here. GO:1990381 names binding to this enzyme class, without assigning deubiquitination to DYRK1A. Proposed replacements: ubiquitin-specific protease binding |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | KEEP AS NON CORE | Summary: Retain the positive FAM53C association as non-core. Reason: The genuine Table S3 and literal interaction records establish a positive yeast-two-hybrid pair. The original distinguishes the polyhistidine-deleted DYRK1A bait from wild type; reference-parent sequence checksums do not authenticate an unmodified experimental insert. Table S3 row724 uses the wild-type-labelled DYRK1A bait and FAM53C nucleotide1016β1179. FAM53C interaction is positive, including targeted follow-up in PMID35914814, but a supported informative molecular partner class was not resolved. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive IGF2BP3 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Original targeted IGF2BP coimmunoprecipitation persisted after benzonase treatment. IGF2BP3 is an RNA-binding protein. Association with it does not establish RNA binding by DYRK1A, and no supported more informative partner-class term was identified in this bounded review. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: Refine the DYNLL1 association to its supported partner class. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. P63167 is dynein light chain DYNLL1. The narrower term names the partner class, without implying that DYRK1A is a dynein motor or that every measured complex functions in transport. Proposed replacements: dynein light chain binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: Refine the SATB1 association to its supported partner class. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. SATB1 is an established sequence-specific DNA-binding transcription factor in its official record. The proposed term describes the binding partner; it does not establish DNA binding or transcription-factor activity of DYRK1A. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive FMR1 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. FMR1 is an RNA-binding translational regulator. Its association does not establish RNA binding by DYRK1A, and the reviewed evidence does not support a more informative molecular binding term. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive ELAVL2 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Q12926 is ELAVL2, a neuronal RNA-binding protein. The pair does not establish RNA binding or a DNA-transcription-factor class for DYRK1A. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive ELAVL3 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Q14576 is ELAVL3, a neuronal RNA-binding protein. The pair does not establish RNA binding or a DNA-transcription-factor class for DYRK1A. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: Refine the TRIP12 association to its supported partner class. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Official TRIP12 functional annotation establishes its E3 ubiquitin-protein-ligase activity. Only binding to that partner class is proposed; its catalysis is not transferred to DYRK1A. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive FAM53C association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. FAM53C interaction is positive, including targeted follow-up in PMID35914814, but a supported informative molecular partner class was not resolved. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive IGF2BP1 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Original targeted IGF2BP coimmunoprecipitation persisted after benzonase treatment. IGF2BP1 is an RNA-binding protein. The association does not establish RNA binding by DYRK1A or a transcription-factor-binding activity. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: Refine the ZMYND8 association to its supported partner class. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. The official ZMYND8 record and experimental GO corepressor annotation establish a chromatin-associated transcription-coregulator role. This class refinement does not claim that DYRK1A recognizes a histone mark or shares ZMYND8 activity. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | KEEP AS NON CORE | Summary: Retain the positive IGF2BP2 association as non-core. Reason: The genuine primary supplementary workbook contains the literal positive interaction in the DYRK1A_Broad human induced-neuron IP-MS dataset. Repeated aggregate rows are not independent assays. This establishes association in a native neuronal protein complex, not a purified interface. Original targeted IGF2BP coimmunoprecipitation persisted after benzonase treatment. IGF2BP2 is an RNA-binding protein. The association does not establish RNA binding by DYRK1A or a transcription-factor-binding activity. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Refine the DCAF7 association to its supported partner class. Reason: The genuine source graph records DYRK1A as prey of the partner bait in a controlled human U2OS AP-MS experiment. The target was not a bait in this dataset, and the edge does not uniquely identify a natural isoform. DCAF7/Han11 is a signaling scaffold, directly supported by PMID20940704 and its official record. The refinement describes binding to that scaffold, not ubiquitin-ligase catalysis by DCAF7 or a new scaffold activity of DYRK1A. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the positive LZTS2 association as non-core. Reason: The genuine source graph records DYRK1A as prey of the partner bait in a controlled human U2OS AP-MS experiment. The target was not a bait in this dataset, and the edge does not uniquely identify a natural isoform. LZTS2 regulates katanin-mediated microtubule severing and localization. That regulatory role does not itself establish that LZTS2 is a motor, a catalytic severing enzyme, or a structural cytoskeletal component. The project-specific policy retains supported generic binding as non-core when no evidence-backed refinement is established. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is integral to the kinase reaction. Reason: The imported protein-kinase domain and ATP-binding-site mappings agree with nucleotide-bound human structures and ATP-dependent substrate assays. This does not assert a separate ATPase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000719 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. InterPro:IPR017441 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0005634 nucleus | EXP PMID:20167603 DYRK1A and DYRK3 promote cell survival through phosphorylati... | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: Recovered PMID20167603 reports nuclear localization of tagged DYRK1 in human U2OS cells; the exact recombinant DYRK species was not separately authenticated. Independent human endogenous and biochemical work corroborates nuclear DYRK1A. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The literal PTN000624548 nucleus IBD is ancestral to the exact target sequence. Experimental annotations on both the target and mammalian homologs are valid descendant grounding, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000624548 SUPPORTS TRANSFER Literal IBD and target descent were reconstructed in PTHR24058; full target sequence matches. Source-side donor experiments and target evidence are distinguished in the reason. |
| GO:0005634 nucleus | IDA PMID:15694837 Dual-specificity tyrosine-phosphorylated and regulated kinas... | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The authentic PMID15694837 abstract reports a nuclear DYRK1A pool and PHYHIP-dependent redistribution to cytoplasm in cotransfected PC12 cells. This is not exclusive localization or a claim that all protein constructs are human. |
| GO:0005634 nucleus | IDA PMID:23415227 Dual specificity kinase DYRK3 couples stress granule condens... | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The PMID23415227 abstract foregrounds DYRK3 and the full target-specific imaging was unavailable. This does not establish misattribution: nuclear DYRK1A is independently demonstrated, so the original experimental assertion is retained with curator deference. |
| GO:0005634 nucleus | IDA PMID:25620562 Chromatin-wide profiling of DYRK1A reveals a role as a gene-... | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The independently recovered original PMID25620562 measures human nuclear/promoter-associated DYRK1A and transcriptional effects. It does not show direct sequence-specific DNA binding. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The SL-0191 mapping is consistent with nuclear pools directly observed in human cells and brain fractions. Nucleoplasm, chromatin and speckle evidence makes the broader nuclear assertion biologically valid and nonexclusive. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: Current mouse Q61214 donor data and the primary brain-localization abstract PMID21878370 support nuclear localization. Independent human observations corroborate the transferred pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: Rat Q63470 has direct nuclear and nuclear-speckle localization evidence, including PMID9748265 and PMID22767602. These studies do not authenticate all historical constructs as human, but support a conserved nuclear pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0005634 nucleus | TAS PMID:9070862 The murine Dyrk protein maps to chromosome 16, localizes to ... | ACCEPT | Summary: DYRK1A has a functional nuclear pool. Reason: The historical human cDNA/genomic study reports nuclear-targeting context. Later direct human localization and transcription assays corroborate nucleus without restricting the protein to a single nuclear subcompartment. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human nucleoplasmic DYRK1A is directly supported. Reason: The HPA target HTML specifically rates nucleoplasm supported, independently of the overall gene score. Nuclear speckles are also supported, whereas centrosome and cytosol have separate uncertain ratings; no images were independently inspected. This annotation denotes a nonexclusive pool. Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1362270 | ACCEPT | Summary: The curated LIN52 phosphorylation reaction locates active DYRK1A in nucleoplasm. Reason: The exact current chain is reaction1362270 β catalytic activity1362272 β human Q13627 entity1362267, residues1β763, with GO:0005654 compartment. The mapping is target-specific, not inferred only from the pathway compartment. Supporting Evidence: Reactome:R-HSA-1362270 |
| GO:0005737 cytoplasm | IDA PMID:15694837 Dual-specificity tyrosine-phosphorylated and regulated kinas... | ACCEPT | Summary: DYRK1A also has a functional cytoplasmic pool. Reason: The authentic PMID15694837 abstract reports PHYHIP-dependent redistribution of DYRK1A to cytoplasm in cotransfected PC12 cells. This positive cellular observation is supported by independent human brain fractionation, without claiming an endogenous human construct-specific mechanism. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A also has a functional cytoplasmic pool. Reason: The mouse Q61214 source supports a cytoplasmic pool, and human brain fractionation independently recovers substantial nonnuclear DYRK1A. Conserved localization is retained without treating it as exclusively soluble cytosol. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0005737 cytoplasm | TAS PMID:24327345 Intracellular distribution of differentially phosphorylated ... | ACCEPT | Summary: DYRK1A also has a functional cytoplasmic pool. Reason: Fractionation detected cytosolic and nuclear DYRK1A in human and mouse brain in addition to its predominant cytoskeletal pool. This supports cytoplasmic localization without assigning every fractionation or phosphorylation result to human material; source-specific Methods and figure locators are in the source guide. Supporting Evidence: |
| GO:0005856 cytoskeleton | IDA PMID:24327345 Intracellular distribution of differentially phosphorylated ... | ACCEPT | Summary: Human brain DYRK1A is associated with the cytoskeletal fraction. Reason: Brain fractionation and coimmunoprecipitation support a predominant cytoskeleton-associated DYRK1A pool and complexes containing actin, neurofilaments and tubulin. The retained colocalizes_with assertion does not claim purified direct binding to each filament or structural-molecule activity. The cache contains the fractionation result; the source guide records the separately accessed original Methods and figures. Supporting Evidence: PMID:24327345 in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000108 | ACCEPT | Summary: Histone phosphorylation links DYRK1A to chromatin reorganization. Reason: The GO:0140857-based mapping is supported by actual histone H3 phosphorylation, promoter occupancy, and changes in HP1, Brg1 and histone marks after DYRK1A perturbation in PMID24820035. Current chromatin-remodeling definition includes chromatin reorganization and is not restricted to ATP-dependent remodeling enzymes; DYRK1A does not acquire ATPase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0140857 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | ACCEPT | Summary: DYRK1A regulates RNA polymerase II transcription through CTD phosphorylation. Reason: The source GO:0008353 is directly supported by human biochemical and cellular CTD assays. The corresponding process is corroborated by gene-local phosphorylation and expression effects, rather than assumed solely because a catalytic GO term exists. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0008353 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0006468 protein phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Protein phosphorylation is the conserved catalytic process. Reason: Rat Q63470 has direct kinase evidence, and human substrate phosphorylation independently supports the transferred process. A general process term is appropriate because DYRK1A acts on several proteins and serine, threonine and tyrosine residues. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0007399 nervous system development | TAS PMID:8769099 Cloning of a human homolog of the Drosophila minibrain/rat D... | KEEP AS NON CORE | Summary: Retain the developmental role as a broad biological context. Reason: The historical human minibrain study links the kinase to nervous-system development and conserved minibrain biology. This broad developmental assertion is retained as contextual to the molecular kinase/transcription/splicing functions rather than equated with a single direct developmental step. Supporting Evidence: |
| GO:0007623 circadian rhythm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A conserved circadian regulatory contribution is supported. Reason: The mouse donor is grounded in PMID20123978: recombinant rat DYRK1A primes mouse CRY2 for subsequent GSK3 phosphorylation, with rodent cellular period effects and mouse liver rhythmic activity. This supports a conserved contextual clock role, not a direct human circadian assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IDA PMID:25620562 Chromatin-wide profiling of DYRK1A reveals a role as a gene-... | ACCEPT | Summary: DYRK1A directly phosphorylates the RNA polymerase II CTD. Reason: The recovered human study directly measures recombinant DYRK1A phosphorylation of CTD Ser2/Ser5, with weaker Ser7 and no Tyr1 signal, and kinase-dependent rescue of gene-local CTD phosphorylation. |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IDA PMID:29849146 Phase-separation mechanism forΒ C-terminal hyperphosphorylati... | ACCEPT | Summary: DYRK1A directly phosphorylates the RNA polymerase II CTD. Reason: The recovered source and supplements support CTD hyperphosphorylation and a contribution of the DYRK1A histidine-rich region. Deleting that region affects CTD association/phosphorylation without eliminating every kinase activity; CYCT1 phase-separation experiments are distinct. |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: DYRK1A directly phosphorylates the RNA polymerase II CTD. Reason: The imported EC2.7.11.23/RHEA10216 mapping agrees with the directly demonstrated human CTD kinase reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:10216 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. EC:2.7.11.23 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0016607 nuclear speck | IDA GO_REF:0000052 | ACCEPT | Summary: Nuclear speckles are one supported DYRK1A compartment. Reason: The HPA target HTML specifically rates nuclear-speckle localization supported. This is distinct from its uncertain centrosome/cytosol entries; no independent image-pixel inspection is claimed. Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear speckles are one supported DYRK1A compartment. Reason: The SL-0186 mapping is corroborated by supported HPA nuclear-speckle localization and splicing-factor colocalization studies. It is a nonexclusive pool rather than a default inferred from the kinase domain. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0186 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. Supporting Evidence: GO_REF:0000044 https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0016607 nuclear speck | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear speckles are one supported DYRK1A compartment. Reason: The current mouse Q61214 source carries nuclear-speckle transfers from rat Q63470/RGD2528 and human Q13627, plus the SL-0186 mapping. This is not presented as a separate direct mouse microscopy experiment. Rat donor PMID22767602 and independently supported human HPA localization supply experimental grounding for the conserved, nonexclusive pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. Supporting Evidence: GO_REF:0000024 https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0016607 nuclear speck | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear speckles are one supported DYRK1A compartment. Reason: Rat Q63470 donor PMID22767602 reports tagged DYRK1A/SRp55 speckle-enriched nuclear colocalization, with separate endogenous human coimmunoprecipitation. Construct species and host cells remain distinct. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. Supporting Evidence: GO_REF:0000024 https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0016607 nuclear speck | TAS PMID:28377597 Dyrk1A overexpression leads to increase of 3R-tau expression... | ACCEPT | Summary: Nuclear speckles are one supported DYRK1A compartment. Reason: The cited original discusses nuclear speckles in the context of alternative-splicing control; human HPA localization and the separately read SRp55 study corroborate the pool. The rat DYRK expression construct in the source is not relabeled as human. Supporting Evidence: https://www.proteinatlas.org/ENSG00000157540-DYRK1A/subcellular |
| GO:0018108 peptidyl-tyrosine phosphorylation | IDA PMID:9748265 Sequence characteristics, subcellular localization, and subs... | ACCEPT | Summary: DYRK1A participates in protein tyrosine phosphorylation, including autophosphorylation. Reason: The historical/rat source supports tyrosine autophosphorylation, and human purified-protein studies independently demonstrate the reaction. The protein performs the phosphate transfer itself; the assertion does not imply a conventional receptor-tyrosine-kinase signaling role. |
| GO:0018108 peptidyl-tyrosine phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A participates in protein tyrosine phosphorylation, including autophosphorylation. Reason: The historical/rat source supports tyrosine autophosphorylation, and human purified-protein studies independently demonstrate the reaction. The protein performs the phosphate transfer itself; the assertion does not imply a conventional receptor-tyrosine-kinase signaling role. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the conserved neuronal axon pool as contextual. Reason: The imported mouse Q61214 localization source is retained; the actual primary localization abstract PMID21878370 examines human/mouse brain and distinguishes neuronal processes, terminals and glial/progenitor nuclear pools. Its full compartment-specific images were not independently recovered. This is not exclusive localization or evidence that every natural product occupies this compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0030425 dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the conserved neuronal dendrite pool as contextual. Reason: The imported mouse Q61214 localization source is retained; the actual primary localization abstract PMID21878370 examines human/mouse brain and distinguishes neuronal processes, terminals and glial/progenitor nuclear pools. Its full compartment-specific images were not independently recovered. This is not exclusive localization or evidence that every natural product occupies this compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0031115 negative regulation of microtubule polymerization | ISS PMID:17906291 DYRK1A-mediated hyperphosphorylation of Tau. A functional li... | KEEP AS NON CORE | Summary: Retain the Tau-dependent microtubule-regulatory context. Reason: The imported mouse Q61214 source PMID17906291 reports DYRK1A-dependent Tau phosphorylation and consequent impairment of Tau-mediated microtubule assembly. The complete assay was unavailable, so no new construct details are asserted. The conserved regulatory effect is retained as a substrate/context-specific consequence rather than a direct severing or polymerase activity of DYRK1A. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0031452 negative regulation of heterochromatin formation | IDA PMID:24820035 DYRK1A phoshorylates histone H3 to differentially regulate t... | ACCEPT | Summary: DYRK1A can oppose promoter-associated heterochromatic features. Reason: The recovered PMID24820035 study directly connects DYRK1A-dependent H3 phosphorylation with promoter chromatin changes, including altered HP1 and Brg1 association after perturbation. H3K9me3 is largely unchanged, and this term does not specifically require constitutive heterochromatin. The claim is bounded to the measured chromatin context rather than global heterochromatin dissolution. Supporting Evidence: |
| GO:0033120 positive regulation of RNA splicing | IBA GO_REF:0000033 | MODIFY | Summary: Represent the demonstrated alternative-exon regulation without a universal positive-splicing sign. Reason: The literal PTN002780677 IBD and target descent are verified; the donor/target evidence is not dismissed because of donor count or target self-inclusion. Together with PMID21215488 and PMID22767602, the actual outcomes depend on cell context and splicing factor, changing alternative products rather than demonstrating a general increase in RNA-splicing rate. GO:0000381 retains the executed regulatory function. It is a biological re-scoping, not a claimed ontology-descendant refinement. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002780677 SUPPORTS TRANSFER Literal IBD and target descent were reconstructed in PTHR24058; full target sequence matches. Source-side donor experiments and target evidence are distinguished in the reason. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: GO_REF:0000033 PMID:22767602 Phosphorylation of SRp55 by Dyrk1A suppressed its ability to promote Tau exon 10 inclusion. |
| GO:0033120 positive regulation of RNA splicing | IDA PMID:28377597 Dyrk1A overexpression leads to increase of 3R-tau expression... | MODIFY | Summary: Represent the demonstrated alternative-exon regulation without a universal positive-splicing sign. Reason: The recovered PMID28377597 experiments use rat DYRK1A reagents and measure Tau exon-10 inclusion/exclusion, with reduced inclusion under increased DYRK activity. Together with PMID21215488 and PMID22767602, the actual outcomes depend on cell context and splicing factor, changing alternative products rather than demonstrating a general increase in RNA-splicing rate. GO:0000381 retains the executed regulatory function. It is a biological re-scoping, not a claimed ontology-descendant refinement. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:28377597 inhibition of Dyrk1A enhanced tau exon 10 inclusion, leading to an increase in 4R-tau/3R-tau ratio |
| GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator | ISS PMID:20736167 Direct association of Sprouty-related protein with an EVH1 d... | KEEP AS NON CORE | Summary: Retain the conserved genotoxic-stress/p53 regulatory context. Reason: PMID20736167 uses mouse-derived DYRK1A constructs and examines SPRED-dependent modulation of p53 acetylation and survival after etoposide. Related DYRK/SIRT1 work has combined DYRK1/DYRK3 depletion and rodent SIRT1 reagents. These positive observations support a contextual regulatory role without establishing a universal direct DYRK1Aβp53 reaction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0045893 positive regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: DYRK1A contributes positively to transcription in defined nuclear contexts. Reason: The target descends from the literal positive-transcription IBD at PTN000624548, grounded in human DYRK1B coactivation evidence. Human DYRK1A CTD and histone studies independently demonstrate positive gene-expression effects, while other substrates can also mediate repression. The term denotes a supported role, not an exclusive direction across every gene. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000624548 SUPPORTS TRANSFER Literal IBD and target descent were reconstructed in PTHR24058; full target sequence matches. Source-side donor experiments and target evidence are distinguished in the reason. |
| GO:0046777 protein autophosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Autophosphorylation is intrinsic to DYRK1A kinase regulation. Reason: The rat Q63470 source is corroborated by direct human biochemical assays. Autophosphorylation includes activation-associated tyrosine and additional residues; weak mature-enzyme tyrosine autophosphorylation prevents an absolute claim that it occurs only once during maturation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0048156 tau protein binding | IPI PMID:25556849 A novel DYRK1A (dual specificity tyrosine phosphorylation-re... | ACCEPT | Summary: DYRK1A recognizes Tau as a directly phosphorylated substrate. Reason: DYRK1A-dependent Tau phosphorylation supports substrate recognition, without establishing a separately measured binding affinity or uniquely authenticated natural DYRK1A splice product. The source guide records the original biochemical assay and construct details. |
| GO:0048156 tau protein binding | ISS PMID:17906291 DYRK1A-mediated hyperphosphorylation of Tau. A functional li... | ACCEPT | Summary: Conserved Tau association supports the substrate-recognition role. Reason: The mouse source PMID17906291 reports DYRK1A-dependent Tau phosphorylation. The normal cache is abstract-only, but independently read mouse-construct association and direct human Tau phosphorylation corroborate the gene-level binding function without fabricating the unavailable assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0048156 tau protein binding | ISS PMID:20736167 Direct association of Sprouty-related protein with an EVH1 d... | ACCEPT | Summary: The cited study supports a conserved DYRK1AβTau association. Reason: PMID20736167 uses mouse-brain-derived DYRK1A/Tau constructs and measures association and SPRED-dependent effects on substrate phosphorylation. This supplies positive ortholog evidence; direct human recombinant phosphorylation independently supports Tau recognition. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61214 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: Tau recognition is supported beyond the cited review statement. Reason: The review summarizes DYRK1A Tau phosphorylation, and direct human substrate assays plus independently read ortholog interaction experiments corroborate this molecular relationship. The review is not treated as a new purified binding experiment. |
| GO:0050321 tau-protein kinase activity | NAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: Tau is a directly demonstrated DYRK1A kinase substrate. Reason: The review-based annotation is corroborated by direct recombinant human DYRK1A phosphorylation of human Tau. The term describes a substrate-specific activity within the broader kinase repertoire, not an exclusive Tau function. |
| GO:0106310 protein serine kinase activity | EXP PMID:20981014 Development of a novel selective inhibitor of the Down syndr... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: PMID20981014 is an authenticated DYRK inhibitor/kinase study; its complete target-specific assay was unavailable. Independent direct human substrate phosphorylation supports the same catalytic function. |
| GO:0106310 protein serine kinase activity | EXP PMID:22998443 Selectivity, cocrystal structures, and neuroprotective prope... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: PMID22998443 is an authenticated DYRK-family inhibitor/structural study. The unavailable target-specific readout is not reconstructed, and independent human biochemical studies support serine activity. |
| GO:0106310 protein serine kinase activity | EXP PMID:23665168 Structures of Down syndrome kinases, DYRKs, reveal mechanism... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: The independently read human biochemical study directly supports serine-containing substrate phosphorylation, with sequence preferences rather than an absolute proline requirement. Supporting Evidence: |
| GO:0106310 protein serine kinase activity | EXP PMID:24239188 Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: The PMID24239188 abstract emphasizes DYRK1B but does not establish absence of DYRK1A experiments. Preserve the curator assertion because human DYRK1A serine activity is independently established. |
| GO:0106310 protein serine kinase activity | IDA PMID:25556849 A novel DYRK1A (dual specificity tyrosine phosphorylation-re... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: The source establishes DYRK1A-dependent Tau phosphorylation; its original site-specific assay supports the retained serine-kinase annotation. The abstract provides broader corroboration, while the source guide identifies the original assay supporting residue specificity. Supporting Evidence: |
| GO:0106310 protein serine kinase activity | IDA PMID:30773093 DYRK1A regulates the recruitment of 53BP1 to the sites of DN... | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: The recovered source measures RNF169 phosphorylation by active DYRK1A and uses mutant controls. Literal site labels vary within the article, so no unsupported harmonized residue numbering is imposed. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein-serine phosphorylation is directly supported DYRK1A chemistry. Reason: The imported RHEA17989 source describes ATP-dependent protein-serine phosphorylation. It matches the official catalytic annotation and actual substrate experiments. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:17989 SUPPORTS TRANSFER Imported mapping source is retained and assessed against current official target/domain or reaction information and actual biological evidence; no source identifier was rewritten. |
| GO:0140857 histone H3T45 kinase activity | IDA PMID:24820035 DYRK1A phoshorylates histone H3 to differentially regulate t... | ACCEPT | Summary: DYRK1A directly phosphorylates histone H3 at Thr45. Reason: PMID24820035 assays GST-H3 and mutant substrates and links DYRK1A-dependent histone phosphorylation to promoter chromatin and expression. This is direct protein-kinase chemistry, not histone methyltransferase or ATP-dependent remodeling activity; the accompanying Ser57 result is not silently substituted for Thr45. Supporting Evidence: |
| GO:1902003 regulation of amyloid-beta formation | IMP PMID:25556849 A novel DYRK1A (dual specificity tyrosine phosphorylation-re... | KEEP AS NON CORE | Summary: Retain the amyloid-output regulatory context. Reason: The source reports effects of DYRK1A depletion, overexpression and inhibition on amyloid-beta production. This contextual regulatory effect supports the non-core annotation without assigning APP cleavage to DYRK1A. The source guide records the original cell model and measured amyloid-beta species. Supporting Evidence: |
| GO:1902996 regulation of neurofibrillary tangle assembly | IDA PMID:25556849 A novel DYRK1A (dual specificity tyrosine phosphorylation-re... | MARK AS OVER ANNOTATED | Summary: Tau insolubility supports related pathology but not the full tangle-assembly claim. Reason: The cached abstract explicitly includes Tau aggregation among the affected endpoints, and the separately accessed original measures insoluble Tau. Aggregation is not itself a demonstration of neurofibrillary-tangle assembly. The over-annotation judgment concerns that distinction; it does not deny the positive aggregation result or rely on missing full text. Detailed assay and figure locators remain in the source guide. Supporting Evidence: PMID:25556849 EHT 5372 inhibits DYRK1A-induced Tau phosphorylation, AΞ² production and AΞ² effects on phospho-Tau, including Tau aggregation. |
| GO:1990935 splicing factor binding | ISS GO_REF:0000024 | ACCEPT | Summary: DYRK1A recognizes and regulates splicing factors. Reason: The rat Q63470 source includes actual SRSF7/9G8 and SRp55 association, phosphorylation and exon-choice assays. PMID22767602 separately detects endogenous human DYRK1AβSRp55 coimmunoprecipitation. The conserved binding role is retained without equating all constructs or claiming universal promotion of splicing. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q63470 SUPPORTS TRANSFER Literal mammalian donor identity/current annotation was traced; exact source assay and organism limits are retained in the reason. Independent human corroboration is identified separately. |
| GO:2000781 positive regulation of double-strand break repair | IDA PMID:30773093 DYRK1A regulates the recruitment of 53BP1 to the sites of DN... | KEEP AS NON CORE | Summary: Retain a defined RNF169-dependent repair-regulatory branch with its opposing knockout phenotype. Reason: PMID:30773093 supports a positive RNF169-dependent branch: DYRK1A phosphorylates RNF169 and kinase-active DYRK1A enhances RNF169-dependent exclusion of 53BP1. The production GO-CAM 617b481400003575 explicitly places this kinase activity upstream of RNF169-mediated homologous-recombination repair. This is the positive mechanistic scope retained here, not a claim that every DYRK1A perturbation increases repair. In the same study, DYRK1A knockout increased the HR reporter significantly in one clone, with a nonsignificant upward trend in the second; RNF169-independent effects on 53BP1 recruitment also remained. PMID:31024071 further separates early 53BP1 recruitment, protein abundance and inhibitor effects. The signed branch is therefore retained as contextual non-core regulation while the net knockout outcome and unresolved mechanism remain explicit. Supporting Evidence: PMID:30773093 Knockdown of RNF169 rescues DYRK1A-mediated inhibition of 53BP1 foci formation. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which RNF169-independent DYRK1A targets or changes in 53BP1 abundance explain why knockout can increase the HR reporter despite the positive RNF169 phosphorylation branch?
Q: Do the natural short products Q13627-3, Q13627-4 and Q13627-5 retain catalytic activity and CTD targeting in cells, given their retained kinase sequence but absent annotated histidine-rich region?
Q: Does endogenous full-length DYRK1A undergo functionally relevant condensation in human cells, and how does this compare with the isolated IDR droplet experiments and cyclin-T1 cellular measurements?
Experiment: Compare acute DYRK1A depletion with independently derived knockout clones and expression-matched wild-type or kinase-dead rescue in the same human cell background. Combine RNF169 perturbation with HR/NHEJ reporters, cell-cycle controls, 53BP1 abundance and early recruitment time courses. Test inhibitors in knockout cells to quantify off-target effects.
Hypothesis: The RNF169-dependent and independent effects of DYRK1A on repair can be separated genetically.
Type: Genetic epistasis, repair reporters and time-resolved recruitment
Experiment: Express sequence-verified Q13627-1 through Q13627-5 at matched levels and compare protein stability, localization, autophosphorylation, peptide-substrate activity, CTD binding and CTD phosphorylation. Use kinase-dead controls and distinguish absence of expression from lack of catalytic function.
Hypothesis: Natural short products differ in substrate targeting without necessarily losing all kinase activity.
Type: Product-resolved biochemical and cellular assays
Experiment: Use endogenous tagging and calibrated expression measurements to test DYRK1A nuclear assemblies, dynamics and CTD phosphorylation in human cells. Compare histidine-region perturbations with intact-protein controls and an expression series; distinguish ordinary speckle association from evidence of condensation rather than relying on a single chemical dispersal treatment.
Hypothesis: The isolated DYRK1A IDR behavior does not by itself establish the behavior of endogenous intact DYRK1A.
Type: Endogenous imaging, expression titration and functional perturbation
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The RNF169-independent mechanism connecting DYRK1A loss to altered 53BP1 behavior and increased HR-reporter output remains unresolved in the inspected human-cell studies.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: DYRK1A phosphorylates RNF169 and promotes its antagonism of 53BP1, but knockout also alters 53BP1 recruitment and abundance through effects not fully reversed by RNF169 depletion. The positive branch and net knockout phenotype are distinct observations.
What would resolve it: Separate acute kinase loss, chronic knockout adaptation and RNF169 epistasis with matched repair reporters and 53BP1 expression/recruitment measurements.
Provenance (the field's own admissions):
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)