DYRK1A is a protein kinase with serine/threonine substrate activity and tyrosine autophosphorylation. Human catalytic-fragment experiments establish that weak tyrosine activity can persist after maturation; substrate preferences are not absolute sequence requirements. A single catalytic core therefore uses GO:0004712, with CTD, histone, Tau and splicing-factor specificity explained in its description and retained in the individual source annotations. Separate ancestor and descendant kinase terms are not duplicated as artificial core units. PMID:23665168(https://pubmed.ncbi.nlm.nih.gov/23665168/)
Human DYRK1A phosphorylates the RNA polymerase II CTD at Ser2 and Ser5, with weaker Ser7 signal. Kinase-dead DYRK1A can restore polymerase occupancy without restoring local CTD phosphorylation. Direct motif-DNA binding was not detected, so chromatin recruitment is not treated as DNA-binding transcription-factor activity. The histidine-rich region contributes to CTD association and hyperphosphorylation, but experimental IDR droplets and cyclin-T1 experiments do not establish that all endogenous DYRK1A forms assemble equivalent condensates. PMID:25620562(https://pubmed.ncbi.nlm.nih.gov/25620562/), PMID:29849146(https://pubmed.ncbi.nlm.nih.gov/29849146/)
Histone H3 phosphorylation and the measured effects on HP1/Brg1 occupancy support chromatin and transcription regulation. This does not imply that DYRK1A is an ATP-dependent chromatin-remodeling motor. Splicing-factor phosphorylation changes Tau exon-10 choice in a substrate- and cell-dependent manner: both increased inclusion and increased exclusion occur in the experiments. Accordingly, two overly directional RNA-splicing assertions are refined to regulation of alternative splicing, preserving their original source identities and the actual rodent construct scopes. The coactivator IBA is retained with literal PAINT grounding and independent target-specific transcription evidence; it does not force a second core or a DNA-binding claim. PMID:24820035(https://pubmed.ncbi.nlm.nih.gov/24820035/), PMID:21215488(https://pubmed.ncbi.nlm.nih.gov/21215488/), PMID:22767602(https://pubmed.ncbi.nlm.nih.gov/22767602/), PMID:28377597(https://pubmed.ncbi.nlm.nih.gov/28377597/)
Human pathogenic variants cause an autosomal dominant neurodevelopmental disorder commonly including microcephaly and intellectual disability. That clinical relationship is distinct from evidence for a particular purified biochemical reaction or substrate. The official target record provides the disease identity and linked genetic literature. UniProt Q13627
All 125 ordinary seeded annotation dictionaries are retained exactly outside their authored review objects. The disposition is 64 ACCEPT, 32 MODIFY, 28 KEEP_AS_NON_CORE and one MARK_AS_OVER_ANNOTATED; there are no NEW, REMOVE, retired or UNDECIDED rows. No source identifier, qualifier, supporting entity or source term is rewritten. Experimental-curator deference matters where an older original remains inaccessible: independently corroborated kinase or location assertions are retained with the source-specific limit made explicit, rather than rejected because a title foregrounds a paralog.
The standing project instruction retains supported, correct generic protein binding as KEEP_AS_NON_CORE when no evidence-backed refinement is established. All 47 binding assertions were independently considered. Supported partner classes include scaffolds, transcriptional coregulators, dynein light chain, ubiquitin ligases, deubiquitinase and DNA-binding transcription factor. These terms state what DYRK1A binds; they do not transfer a partner's catalysis, RNA binding or transcriptional activity. A purified interface is not required merely to classify a verified partner, but assay type, fragment boundaries and native-context limits remain explicit.
Positive PHYHIP, SPRED1/2, TROAP, LZTS2, FAM53C, KPRP and RNA-binding-partner associations remain non-core where a suitable informative binding refinement was not established. In particular, SPRED recruitment of NF1 is not SPRED GTPase catalysis, LZTS2 regulation of severing machinery is not severing-enzyme activity, and IGF2BP or ELAVL association does not make DYRK1A an RNA-binding protein. USP54 is assessed as an active deubiquitinase rather than assumed inactive from family membership.
The portable evidence package reproduces four primary data selections from authentic saved inputs and publicly identified source URLs. It preserves original cells, fields, accession groups and experiment direction rather than replacing them with biological interpretations.
Absence from a current interaction database capture is not a negative assay. The target-specific supplement for PMID:35016035 was unavailable, and the captured interaction queries did not recover that exact pair; independent DCAF7 associations and its scaffold identity support retention without pretending that the missing target record was read.
Human-brain fractionation supports nuclear, cytosolic and cytoskeletal pools. Large coimmunoprecipitated complexes do not establish homomultimer stoichiometry or purified binding to each cytoskeletal component. The HPA target HTML specifically classifies nucleoplasm and nuclear speckles as supported, while centrosome and cytosol are uncertain; an overall XML score is not substituted for those individual-location assessments. Positive other-source cytoplasmic observations remain valid. No image-pixel interpretation is claimed for this HPA assessment. PMID:24327345(https://pubmed.ncbi.nlm.nih.gov/24327345/), HPA
The literal PTHR24058 tree and MSA contain the human target sequence exactly. Five IBA assertions descend from their specified IBD nodes; the target's own experimental donor status is legitimate evidence, not circularity. The coactivator donor is human DYRK1B, while several location and splicing donors are mouse or rat. For mouse nuclear speckles, the current donor record itself includes human/rat transfers rather than an independently reconstructed mouse microscopy experiment. Axon and dendrite assignments have separate mouse IDA donor records, with their original full-body access limit preserved. No donor-count threshold or similarity score replaces the actual phylogenetic judgment.
The five official products are 763, 754, 529, 525 and 584 residues. They all retain the annotated kinase sequence; only the first two retain the annotated histidine-rich region. The 754-residue form deletes residues 70–78 relative to the displayed product. Shorter alternative tails do not by themselves prove catalytic inactivity or equal function. Experimental catalytic fragments, tagged proteins and rodent constructs are not automatically mapped onto current human natural products by a shared name or host cell.
The amyloid-output and Tau-insolubility experiments are kept at their measured scope. Human cell kinase perturbations change APP-derived amyloid output, while the sarkosyl-insoluble Tau experiment uses rat cortical neurons. Insoluble Tau is not itself a demonstrated human neurofibrillary-tangle-assembly endpoint, so that specific assembly assertion is marked over-annotated while retaining the positive aggregation-related evidence. PMID:25556849(https://pubmed.ncbi.nlm.nih.gov/25556849/)
DYRK1A's DNA-repair effects depend on perturbation and context. RNF169 phosphorylation and overexpression-associated changes in 53BP1 are real, but knockout increases the reported homologous-recombination endpoint, and early recruitment phenotypes are not fully explained by RNF169. The curated positive RNF169 branch and GO-CAM context are preserved as non-core, without claiming all double-strand-break repair is positively regulated. Harmine effects persisting in knockout cells also prevent inhibitor phenotypes from serving as uniquely DYRK1A-specific evidence. PMID:30773093(https://pubmed.ncbi.nlm.nih.gov/30773093/), PMID:31024071(https://pubmed.ncbi.nlm.nih.gov/31024071/)
Ordinary fetch produced genuine machine records and publication caches. The configured Falcon attempt failed with an Edison authorization response, and the configured perplexity-lite fallback returned an authentication/quota failure. No replacement provider report was invented; these notes and the source guide record manual source review instead.
Machine cache flags remain unchanged. Separate authentic originals materially extended several abstract-only caches, including PMC originals for the SPRED, SIRT1, histone and splicing studies, an institutional PDF for the CTD-kinase study, and indexed original access for the inhibitor/Tau study. Bibliographic verification is distinguished from access to a specific target measurement. Each reference's full_text_unavailable flag records the actual source-specific body-access assessment, not a copied cache-wide flag. A false flag does not imply that every page, supplement or image was inspected; the source guide specifies the operative scope.
No new supporting-text quotation is introduced in the annotation rows, core or reference findings. The entire evidence assessment is paraphrased with reference anchors; the portable extractor reproduces source measurements rather than authored scientific conclusions.
This follow-up preserves all 125 imported assertions and all existing actions, replacements, products and core terms. It clarifies the positive RNF169-dependent repair branch separately from the opposing knockout reporter result, and exposes a mechanistic knowledge gap plus targeted questions and experiments. It does not neutralize the signed branch simply because whole-cell perturbations have additional effects.
The source guide now gives the actual author-upload route and Methods/Figure locators for PMID:25556849. The abstract-only machine cache remains unchanged; no supporting-text quotation is fabricated from it. The tangle-assembly over-annotation judgment rests on the measured aggregation endpoint rather than on source inaccessibility or an automatic rejection of nonhuman evidence. Human-brain fractionation and immunoprecipitation support the cytoskeleton-associated pool. USP54's current official experimental function statements support its partner class without transferring protease activity to DYRK1A.
One exact ten-word caption anchor from PMID:30773093 is added once to the repair review. No new source assertion, process annotation or core function is introduced. The concise disease sentence repeats the already recorded official human disease relationship. The earlier source-access and construct limitations remain operative. No publication cache, imported source dictionary or prior note text is rewritten.
Short cache-exact excerpts now anchor dual-specificity catalysis, Han11 scaffold binding, alternative Tau exon choice, cytoskeletal association, and the Tau aggregation endpoint. Selected reference findings record the corresponding biological scope; repeated interactions with the same partner cite the same source without duplicating quotations. The DYRK1A IDR experiment remains distinct from intact-protein or live-cell cyclin-T1 condensation.
PMID:25556849 already mentions Tau aggregation in its cached abstract. The source is therefore not limited to a phosphorylation endpoint. The retained over-annotation judgment distinguishes aggregation from demonstrated neurofibrillary-tangle assembly; the original assay details remain in the source guide. Shorter annotation reasons retain the original evidence while separating cache-verifiable statements from source-specific Methods. All 125 source records, decisions, product identities, and the core function remain unchanged.