CHEK2 encodes CHK2, an FHA-domain-containing protein serine/threonine kinase that couples DNA damage signaling to checkpoint control, substrate stability and apoptotic responses. ATM-dependent priming and regulated self-association promote activation-loop autophosphorylation. Nuclear CHK2 phosphorylates regulatory proteins including checkpoint phosphatases and factors controlling p53 signaling, transcription and DNA-repair pathway choice. Its action is regulatory rather than direct DNA rejoining. PML-associated nuclear pools and context-dependent extranuclear distributions have been reported. Alternative splicing produces proteins with different domain content and activity; the canonical 543-residue enzyme is not representative of every product.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000077 DNA damage checkpoint signaling | TAS PMID:10617473 Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndro... | ACCEPT | Summary: DNA damage checkpoint signaling is a defining CHEK2 role. Reason: Independent human kinase and checkpoint experiments establish a performed signaling role through substrate phosphorylation. The original TAS source remains intact; the clinical mutation report is not presented as the sole biochemical demonstration. |
| GO:0000077 DNA damage checkpoint signaling | TAS PMID:9889122 A human homologue of the checkpoint kinase Cds1 directly inh... | ACCEPT | Summary: DNA damage checkpoint signaling is a defining CHEK2 role. Reason: Independent human kinase and checkpoint experiments establish a performed signaling role through substrate phosphorylation. The original TAS source remains intact; the clinical mutation report is not presented as the sole biochemical demonstration. |
| GO:0000086 G2/M transition of mitotic cell cycle | IMP PMID:16481012 Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3)... | KEEP AS NON CORE | Summary: Retain the G2/M transition role at checkpoint-regulatory scope. Reason: The original PLK3 study reports CHK2 activation and a downstream G2/M checkpoint. CHEK2 regulates transition timing through signaling rather than acting as a spindle motor. The original abstract is available; its detailed full assay was not recovered. Independent human CHK2 checkpoint studies corroborate this broad regulatory role. |
| GO:0000781 chromosome, telomeric region | IDA PMID:15149599 Telomere shortening triggers senescence of human cells throu... | UNDECIDED | Summary: The exact telomeric colocalization assertion remains unresolved. Reason: The original human fibroblast paper reports telomeric damage foci in its abstract, but the target-specific CHK2 localization panel and full Methods were not recovered. Preserve the colocalizes_with qualifier and experimental source; neither the title nor this access gap demonstrates incorrect curation. Supporting Evidence: |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Specify the experimentally established protein serine/threonine kinase activity. Reason: The original integrated electronic sources are retained. Direct human CHK2 catalysis and activation-loop experiments support a Ser/Thr kinase refinement; the mouse donor and domain assignments are not treated as evidence that every alternative product is equally active. Proposed replacements: protein serine/threonine kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. The PAINT ancestral node is retained without reconstructing its history; descendant number and target self-reference are not objections. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN005196447 UNRESOLVED Actual ancestral PAINT assertion preserved; node history was not reconstructed. Target evidence and compartment scope are assessed separately, without donor-count or target-self-reference objections. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage. | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. The original abstract and the author’s primary thesis support E2F1 S364 phosphorylation; the thesis is not represented as the recovered journal body. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16794575 Trans-activation of the DNA-damage signalling protein kinase... | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. The exact original evidence and source are preserved; independent biochemical support does not alter source provenance. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. PMID:37943659 reports TRIM32 S55 phosphorylation in its abstract; its detailed full experiment remains inaccessible, while the same broad catalytic activity is independently established. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. The exact original evidence and source are preserved; independent biochemical support does not alter source provenance. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:9836640 Linkage of ATM to cell cycle regulation by the Chk2 protein ... | ACCEPT | Summary: Retain intrinsic protein serine/threonine kinase activity. Reason: Direct human CHK2 biochemical assays establish serine/threonine phosphorylation, including activation-loop phosphorylation. The exact original evidence and source are preserved; independent biochemical support does not alter source provenance. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-349426 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for MDM4 phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. Supporting Evidence: Reactome:R-HSA-349426 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for BRCA1 phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. Supporting Evidence: Reactome:R-HSA-5683801 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-6804266 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for TTC5/STRAP phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. Supporting Evidence: Reactome:R-HSA-6804266 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-69608 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for CDC25A phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. CDC25A phosphorylation is distinct from the contested claim that CHK2 generally triggers its destruction; the current event itself notes the later CHK1/Ser76 qualification. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-69685 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for TP53 phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-75809 | ACCEPT | Summary: Retain the curated substrate-phosphorylation activity. Reason: The exact Reactome event assigns CHEK2 as a catalyst for CDC25C phosphorylation, consistent with human kinase biochemistry. This is CHEK2 catalysis, not transfer of another pathway member’s activity. |
| GO:0005515 protein binding | IPI PMID:11298456 The ATM-Chk2-Cdc25A checkpoint pathway guards against radior... | MODIFY | Summary: Refine the verified CDC25A interaction to protein phosphatase binding. Reason: The exact human MINT co-immunoprecipitation record establishes CDC25A association. Protein phosphatase binding identifies that demonstrated partner class, whereas CHEK2 kinase activity describes its phosphate-transfer reaction. The later disagreement concerns CDC25A turnover, not the positive association or phosphorylation evidence. The class refinement does not require a purified interface or assign phosphatase activity to CHEK2. Proposed replacements: protein phosphatase binding |
| GO:0005515 protein binding | IPI PMID:12402044 PML-dependent apoptosis after DNA damage is regulated by the... | KEEP AS NON CORE | Summary: Retain the PML association with historical construct nomenclature explicit. Reason: The original selected full Results and Methods report endogenous co-IP and colocalization plus PML phosphorylation. The construct is historical PML3, GenBank X63131, 633 residues; the source asserts P29590-5. Its length is compatible with current PML-IV, but no independent complete sequence comparison is claimed. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:12493754 Polo-like kinase 1 and Chk2 interact and co-localize to cent... | MODIFY | Summary: Specify PLK1 as the bound protein kinase. Reason: Exact curated tagged and endogenous human co-IP records support CHEK2–PLK1 association. The verified partner-class definition supports kinase binding without claiming that CHEK2 activates PLK1 or performs spindle-motor work. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5C-1 records include GST pull-down and tagged HEK293 co-immunoprecipitation (Figures 2/3). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding Supporting Evidence: PMID:15380617 Chk2 associated with the B' regulatory subunit file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5C-2 records include yeast two-hybrid and GST pull-down (Figures 1A/2). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5C-3 records include yeast two-hybrid, GST pull-down and tagged HEK293 co-immunoprecipitation (Figures 1A/2/3). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5A records include yeast two-hybrid and GST pull-down (Figures 1A/2). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5B records include yeast two-hybrid and GST pull-down (Figures 1A/2). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:15380617 Regulation of Chk2 phosphorylation by interaction with prote... | MODIFY | Summary: Refine the demonstrated PP2A regulatory-subunit association to PP2A binding. Reason: The exact PPP2R5E records include yeast two-hybrid and GST pull-down (Figures 1A/2). The authentic PMID:15380617 abstract independently reports PP2A A and C subunits in CHK2-associated complexes. The original full body remains inaccessible; the product-specific assay details come from the literal curated interaction records. GO:0051721 specifies binding to PP2A, not possession of phosphatase catalytic activity. Contact through a regulatory B subunit supports that binding class; it does not make the B subunit or CHEK2 a phosphatase, or establish a universal isolated holoenzyme interface. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:16477038 Human cytomegalovirus inhibits a DNA damage response by misl... | KEEP AS NON CORE | Summary: Retain human cytomegalovirus pp65 association. Reason: Full target Results report CHK2 co-IP with pp65 in infected human fibroblast preparations. This supports association with a viral protein-containing complex; it is not a purified binary binding assay or a constitutive host-cell function. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17157788 Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates ... | MODIFY | Summary: Refine AATF association to transcription coregulator binding. Reason: The exact human AATF/CHK2 interaction records include endogenous co-IP and phosphorylation assays. AATF is a transcriptional cofactor; this class term does not assign DNA-binding transcription-factor activity to AATF or CHEK2. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple... | MODIFY | Summary: Refine pRB association to transcription corepressor binding. Reason: Original full Results and exact MINT records establish CHEK2 association with the pRB large pocket and endogenous pRB in human cells. Its established corepressor role supports this binding class, without making CHEK2 itself a corepressor. Proposed replacements: transcription corepressor binding |
| GO:0005515 protein binding | IPI PMID:17525332 ATM and ATR substrate analysis reveals extensive protein net... | MODIFY | Summary: Specify association with the VCP ATPase. Reason: Endogenous and tagged human co-immunoprecipitation records identify VCP association, and its official protein record establishes VCP as an ATPase. ATPase binding captures this demonstrated partner class in addition to CHEK2 kinase activity. The assay does not establish that CHEK2 regulates VCP catalysis or acts as an ATP-driven mechanical motor. Proposed replacements: ATPase binding |
| GO:0005515 protein binding | IPI PMID:17525332 ATM and ATR substrate analysis reveals extensive protein net... | KEEP AS NON CORE | Summary: Retain GINS2 association at the recorded assay scope. Reason: The exact human co-IP records support GINS2 association. They do not by themselves demonstrate CHEK2 participation in DNA-unwinding chemistry or a defined replication-initiation complex role. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:18644861 Regulation of Chk2 ubiquitination and signaling through auto... | KEEP AS NON CORE | Summary: Retain CUL1 association in the CHK2 ubiquitination context. Reason: The independently recovered full primary supports CHK2 ubiquitination/signaling and CUL1-containing complex association. CUL1 is a scaffold subunit of an E3 assembly, not an independently catalytic ubiquitin ligase. Retain the broad pair assertion without transferring ubiquitin-ligase activity to CHEK2. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18667510 The DNA damage sensors ataxia-telangiectasia mutated kinase ... | KEEP AS NON CORE | Summary: Retain association with the HCV NS5B processed product. Reason: The source reports endogenous CHK2–NS5B co-IP from human HCV-replicon cells and tagged coexpression assays. The exact processed-product accession is preserved; this is not an assertion that CHEK2 binds every region of the HCV polyprotein or has RNA-polymerase activity. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:18971944 Chk2-dependent phosphorylation of XRCC1 in the DNA damage re... | KEEP AS NON CORE | Summary: Retain XRCC1 binding at the curated experimental scope. Reason: Exact human MINT records report endogenous association and pull-down assays, including the specified XRCC1 region. These support the pair even though the original full body was not recovered here; no binary interface or independent base-excision-repair chemistry is inferred from the interaction alone. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:20126263 A mitotic phosphorylation feedback network connects Cdk1, Pl... | MODIFY | Summary: Retain PLK1 binding as a kinase-partner refinement. Reason: This full source demonstrates PLK1 phosphorylation of CHK2 and changes in its FHA interactions, but does not establish a stable binary cellular complex. The original IPI assertion and independent PMID:12493754 co-IP support the kinase-binding class; do not redescribe substrate phosphorylation as the missing co-IP. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:21070773 Per3, a circadian gene, is required for Chk2 activation in h... | KEEP AS NON CORE | Summary: Retain PER3 association in the activation context. Reason: Two exact MINT records report tagged and endogenous human co-IP. This supports the interaction, not an autonomous circadian oscillator activity of CHEK2. Original full-source construct details were not independently recovered. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | KEEP AS NON CORE | Summary: Retain association with the SARS coronavirus nsp13 product. Reason: The exact curated Y2H and LUMIER records support the processed nsp13 interaction in heterologous assays. Preserve the original viral product feature and assay limits; neither helicase activity nor a demonstrated infection-stage mechanism is transferred to CHEK2. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:23178491 CHK2 kinase promotes pre-mRNA splicing via phosphorylating C... | MODIFY | Summary: Refine the PPM1G association to protein phosphatase binding. Reason: The exact PPM1G association supports binding to a verified protein phosphatase, not phosphatase catalysis by CHEK2. The source uses TAP-purified CHK2 complexes; no purified binary interaction is established. Proposed replacements: protein phosphatase binding |
| GO:0005515 protein binding | IPI PMID:23178491 CHK2 kinase promotes pre-mRNA splicing via phosphorylating C... | MODIFY | Summary: Refine USP7 association to ubiquitin-specific protease binding. Reason: USP7 is a verified ubiquitin-specific protease; the definition identifies the bound partner and does not require regulation of its catalysis. The positive source is TAP complex association, not a purified binary interface. Proposed replacements: ubiquitin-specific protease binding |
| GO:0005515 protein binding | IPI PMID:23178491 CHK2 kinase promotes pre-mRNA splicing via phosphorylating C... | MODIFY | Summary: Specify CDK11B as the bound kinase. Reason: The exact Q9UQ88-1 interaction is supported by tagged and endogenous co-immunoprecipitation and substrate phosphorylation in the full paper. Protein serine/threonine kinase binding records CDK11B as the demonstrated kinase partner, separately from CHEK2 kinase activity. The source’s CDK11 S737 numbering remains distinct from current alternative-product numbering; the binding-class refinement does not establish additional physiological regulation beyond the reported experiments. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:24825908 Collaborator of ARF (CARF) regulates proliferative fate of h... | UNDECIDED | Summary: The exact CARF physical-interaction source remains unresolved. Reason: Full target-specific Results were inspected, but the resolved CHK2 evidence is a phosphorylation/signaling readout after CARF perturbation. The demonstrated co-IP partners in that text do not settle this exact pair, and no matching bounded IntAct/MINT record was recovered. This is a source-link uncertainty, not proof that CARF cannot bind CHEK2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25640309 Systematic identification of molecular links between core an... | KEEP AS NON CORE | Summary: Retain the exact IL24 screening interaction. Reason: Positive source-linked yeast two-hybrid and tagged human-cell co-immunoprecipitation records support the pair. These assays do not independently establish native encounter, receptor activity or a CHEK2-specific physiological pathway. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:25640309 Systematic identification of molecular links between core an... | MODIFY | Summary: Refine RNF20 association to ubiquitin protein ligase binding. Reason: The exact positive Y2H/co-IP records and the verified E3 partner identity support the same binding-class interpretation used for RNF8. This does not assign ligase activity or a proved ubiquitination mechanism to CHEK2. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:25640309 Systematic identification of molecular links between core an... | KEEP AS NON CORE | Summary: Retain the exact LRATD2/FAM84B screening interaction. Reason: Positive source-linked yeast two-hybrid and tagged human-cell co-immunoprecipitation records support the pair. These assays do not independently establish native encounter, receptor activity or a CHEK2-specific physiological pathway. Supported generic binding is retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, because no further evidence-backed informative class is established here. |
| GO:0005515 protein binding | IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ... | UNDECIDED | Summary: The exact TNKS1BP1 physical-interaction source remains unresolved. Reason: Full target-specific Results were inspected, but the resolved CHK2 evidence is a phosphorylation/signaling readout after TNKS1BP1 perturbation. The demonstrated co-IP partners in that text do not settle this exact pair, and no matching bounded IntAct/MINT record was recovered. This is a source-link uncertainty, not proof that TNKS1BP1 cannot bind CHEK2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Refine the PPM1G association to protein phosphatase binding. Reason: The exact PPM1G association supports binding to a verified protein phosphatase, not phosphatase catalysis by CHEK2. The curated experiment specifies a CHEK2 367–543 region and variant context; this is fragment/construct capability, not proof of full-length wild-type interaction in every cell. Proposed replacements: protein phosphatase binding |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | MODIFY | Summary: Refine the mapped PP2A-binding motif at the peptide-assay scope. Reason: The exact positive PMID:37219487 IntAct phage-display record maps the CHEK2 interacting region to residues 68–79 and PPP2R5A to residues 1–486. The primary platform selects motif-containing peptides against protein domains, with tag-negative selection; this record is not a full-length cellular CHEK2 assay or an independent CHEK2 affinity measurement. As for the earlier PP2A associations, GO:0051721 describes binding through the PP2A regulatory subunit without assigning phosphatase activity to that subunit or to CHEK2. The refinement remains outside the catalytic core and does not assert constitutive native holoenzyme binding. Proposed replacements: protein phosphatase 2A binding |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | MODIFY | Summary: Refine USP7 association to ubiquitin-specific protease binding. Reason: USP7 is a verified ubiquitin-specific protease; the definition identifies the bound partner and does not require regulation of its catalysis. The exact record is fluorescence-polarization binding between short CHEK2 and USP7 fragments, with mutation-effect features. Retain that peptide capability without presenting every recorded mutant as a full-length wild-type physiological interaction. Proposed replacements: ubiquitin-specific protease binding |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding supplies the kinase reaction. Reason: Purified human CHK2 directly transfers phosphate from ATP to protein substrates. The kinase-domain mapping is corroborated biochemically; ATP binding is an integral catalytic property rather than a separate motor function. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The nucleus is a principal functional compartment. Reason: Human endogenous localization and damage-signaling substrate assays support nuclear CHEK2. The PAINT or UniProt source remains unchanged; the assertion does not require exclusive nuclear residence or identical localization of every alternative product. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN005196447 UNRESOLVED Actual ancestral PAINT assertion preserved; node history was not reconstructed. Target evidence and compartment scope are assessed separately, without donor-count or target-self-reference objections. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: The nucleus is a principal functional compartment. Reason: Human endogenous localization and damage-signaling substrate assays support nuclear CHEK2. The PAINT or UniProt source remains unchanged; the assertion does not require exclusive nuclear residence or identical localization of every alternative product. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain nucleoplasm as a core CHEK2 location. Reason: Official HPA human ICC/IF records and the inspected Hep-G2 image support nucleoplasmic signal. The additional Golgi staining is not imported as an unrequested new assertion; nuclear substrate assays independently support functional context. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Retain nucleoplasm as a core CHEK2 location. Reason: Official HPA human ICC/IF records and the inspected Hep-G2 image support nucleoplasmic signal. The additional Golgi staining is not imported as an unrequested new assertion; nuclear substrate assays independently support functional context. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-349426 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-349426 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-5683735 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683774 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-5683774 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683792 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-5683792 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-5683801 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6804266 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. Supporting Evidence: Reactome:R-HSA-6804266 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69608 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69685 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75809 | ACCEPT | Summary: Retain the curated nucleoplasmic reaction context. Reason: The exact human Reactome event locates the relevant CHEK2-containing entity or reaction in nucleoplasm. Recruitment, activation, autophosphorylation and substrate phosphorylation are distinct event roles; localization does not imply that CHEK2 catalyzes an upstream ATM reaction. Independent human nuclear observations corroborate the compartment. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | UNDECIDED | Summary: The inferred cytoplasmic active pool is not resolved at the required functional scope. Reason: The PAINT ancestral assertion is retained, and cytoplasmic CHK2 is not considered biologically impossible. Infection-dependent relocation alone does not demonstrate activity in that pool; the detailed oxidative-stress primary assays remain inaccessible. The uncertainty concerns functional compartment scope, not donor count or target-specific loss. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN005196447 UNRESOLVED Actual ancestral PAINT assertion preserved; node history was not reconstructed. Target evidence and compartment scope are assessed separately, without donor-count or target-self-reference objections. |
| GO:0006302 double-strand break repair | IMP PMID:18317453 The checkpoint kinases Chk1 and Chk2 regulate the functional... | MODIFY | Summary: Refine repair participation to regulation of homologous-recombination repair. Reason: The original primary establishes CHK2 phosphorylation of BRCA2 T3387 and context-dependent BRCA2/RAD51 associations and irradiation-induced RAD51 foci. This is performed regulatory work, not direct strand-exchange or DNA-rejoining chemistry. The mouse mutant and human protein assays remain distinguished; the CHK1–RAD51 T307 mechanism is not transferred. Figure 1D compares wild-type BRCA2 C terminus and T3387A in the Chk2 kinase reaction, with silver-stained protein amounts; the full-text anchor was read in the authentic author-uploaded original, while the cached abstract is preserved. Proposed replacements: regulation of double-strand break repair via homologous recombination Supporting Evidence: |
| GO:0006302 double-strand break repair | TAS Reactome:R-HSA-5693606 | MODIFY | Summary: Refine the pathway assertion to regulation of double-strand break repair. Reason: The exact Reactome branch contains CHEK2 recruitment/activation and CHEK2-catalyzed BRCA1 phosphorylation. That performed regulatory step supports the broader repair-regulation term without assigning BRCA1/53BP1 pathway chemistry or direct rejoining to CHEK2. This lateral refinement preserves the original event source. Proposed replacements: regulation of double-strand break repair Supporting Evidence: Reactome:R-HSA-5693606 Reactome:R-HSA-5683801 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage. | KEEP AS NON CORE | Summary: Retain transcriptional regulation through a phosphorylated transcription factor. Reason: The original abstract and author thesis support E2F1 phosphorylation and altered substrate properties. Thesis reporter tests did not show a direct change after CHK2 overexpression. Retain broad regulatory context without assigning intrinsic transcription-factor activity or universal promoter stimulation. |
| GO:0006468 protein phosphorylation | IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage. | ACCEPT | Summary: Protein phosphorylation is CHEK2’s performed biochemical process. Reason: The original E2F1 report and independently inspected human kinase experiments establish phosphate transfer to protein substrates. The author thesis provides a recombinant E2F1 S364 assay, separately from the unrecovered journal body. |
| GO:0006974 DNA damage response | IDA PMID:24550317 PARP1-dependent recruitment of KDM4D histone demethylase to ... | ACCEPT | Summary: Retain DNA damage response at the supported signaling scope. Reason: Independent human kinase/checkpoint experiments support this defining signaling role. The full original KDM4D paper measures CHK2 T68 as a DDR readout; preserve its acts_upstream_of_or_within qualifier rather than describing that experiment as a direct CHEK2 repair assay. |
| GO:0006974 DNA damage response | IMP PMID:16481012 Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3)... | ACCEPT | Summary: Retain DNA damage response at the supported signaling scope. Reason: Independent human kinase/checkpoint experiments support this defining signaling role. The original source identity remains intact; upstream activation and downstream substrate phosphorylation are distinguished. |
| GO:0006974 DNA damage response | TAS PMID:9836640 Linkage of ATM to cell cycle regulation by the Chk2 protein ... | ACCEPT | Summary: Retain DNA damage response at the supported signaling scope. Reason: Independent human kinase/checkpoint experiments support this defining signaling role. The original source identity remains intact; upstream activation and downstream substrate phosphorylation are distinguished. |
| GO:0006974 DNA damage response | TAS PMID:9889122 A human homologue of the checkpoint kinase Cds1 directly inh... | ACCEPT | Summary: Retain DNA damage response at the supported signaling scope. Reason: Independent human kinase/checkpoint experiments support this defining signaling role. The original source identity remains intact; upstream activation and downstream substrate phosphorylation are distinguished. |
| GO:0006979 response to oxidative stress | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | UNDECIDED | Summary: The specific stress/autophagy assertion awaits full source-level resolution. Reason: The authentic PMID:37943659 abstract positively reports ATM–CHK2–TRIM32 signaling and ATG7 ubiquitination under oxidative/metabolic stress. Bounded publisher and repository attempts did not recover the full Results/Methods needed to resolve this exact stimulus, assay and species scope. Preserve the experimental assertion; no negative conclusion or removal follows from the access gap. Curated GO-CAM models 654d809000001587 and 654d809000001692 positively place CHEK2 kinase activity in the ATM–CHK2–TRIM32–ATG7 signaling context using PMID:37943659. This is affirmative curated support, not a missing-model claim; it does not provide the inaccessible primary assay details needed to resolve this source-specific judgment. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IDA PMID:12402044 PML-dependent apoptosis after DNA damage is regulated by the... | ACCEPT | Summary: Retain damage-induced apoptotic signaling as a CHEK2 output. Reason: CHEK2 substrate phosphorylation contributes to damage-triggered apoptotic signaling, rather than executing terminal proteolysis. The original full human PML experiments include phosphorylation-site and cell-death assays. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000117 | ACCEPT | Summary: Retain damage-induced apoptotic signaling as a CHEK2 output. Reason: CHEK2 substrate phosphorylation contributes to damage-triggered apoptotic signaling, rather than executing terminal proteolysis. The authentic ARBA rule outputs this term; independent human target experiments support it without a new family-tree reconstruction. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IMP PMID:12717439 Chk2 activates E2F-1 in response to DNA damage. | ACCEPT | Summary: Retain damage-induced apoptotic signaling as a CHEK2 output. Reason: CHEK2 substrate phosphorylation contributes to damage-triggered apoptotic signaling, rather than executing terminal proteolysis. The original abstract and author thesis support E2F1-dependent apoptosis in human cells; the journal body remains unavailable. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IMP PMID:18644861 Regulation of Chk2 ubiquitination and signaling through auto... | ACCEPT | Summary: Retain damage-induced apoptotic signaling as a CHEK2 output. Reason: CHEK2 substrate phosphorylation contributes to damage-triggered apoptotic signaling, rather than executing terminal proteolysis. The original full autophosphorylation/ubiquitination study supports the damage-response signaling context, with mutant effects kept separate from an intrinsic E3 activity. |
| GO:0016605 PML body | IDA PMID:12402044 PML-dependent apoptosis after DNA damage is regulated by the... | KEEP AS NON CORE | Summary: Retain PML-body localization at the tested nuclear-subdomain scope. Reason: The original human PML study reports CHK2 colocalization and association with PML-containing nuclear bodies. This is a supported signaling context within the nucleus, without requiring residence in every PML body or an exclusively PML-bound kinase pool. Supporting Evidence: |
| GO:0016605 PML body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain PML-body localization at the tested nuclear-subdomain scope. Reason: The original human PML study reports CHK2 colocalization and association with PML-containing nuclear bodies. This is a supported signaling context within the nucleus, without requiring residence in every PML body or an exclusively PML-bound kinase pool. Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:16481012 Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3)... | MODIFY | Summary: Specify the PLK3 serine/threonine kinase partner. Reason: The original source and exact kinase partner are retained. The available primary abstract explicitly reports PLK3-dependent priming and CHK2 activation; this is compatible with the existing kinase-binding assertion, without claiming CHEK2 itself performs PLK3 priming or a newly verified purified interface. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0030163 protein catabolic process | IMP PMID:11298456 The ATM-Chk2-Cdc25A checkpoint pathway guards against radior... | UNDECIDED | Summary: The original CDC25A catabolic assertion is contested and remains unresolved. Reason: The original abstract reports CHK2-associated CDC25A destruction, but its full body was not recovered. Independent full PMID:18480045 shows CHK2 phosphorylation at other sites without effective Ser76-dependent SCF-betaTRCP ubiquitination, and preserved irradiation-induced CDC25A turnover in human CHK2-null HCT116 cells. These findings challenge that specific mechanism while leaving other contexts open; they do not negate binding or all kinase-dependent catabolic regulation. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IEA GO_REF:0000117 | ACCEPT | Summary: Retain p53-mediated DNA damage signaling. Reason: CHEK2 performs substrate phosphorylation within this pathway. Official electronic/Reactome provenance is preserved; the direct p53/MDM4 reactions and independently established kinase function support signaling without making CHEK2 the p53 transcription factor. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | TAS Reactome:R-HSA-69563 | ACCEPT | Summary: Retain p53-mediated DNA damage signaling. Reason: CHEK2 performs substrate phosphorylation within this pathway. Official electronic/Reactome provenance is preserved; the direct p53/MDM4 reactions and independently established kinase function support signaling without making CHEK2 the p53 transcription factor. |
| GO:0031573 mitotic intra-S DNA damage checkpoint signaling | IMP PMID:11298456 The ATM-Chk2-Cdc25A checkpoint pathway guards against radior... | ACCEPT | Summary: Retain the intra-S damage-checkpoint signaling role. Reason: The original positive checkpoint assertion is consistent with CHEK2’s established signaling function. Its detailed full experiment was not recovered, and later CDC25A turnover results limit that proposed mechanism. Retention does not make CDC25A destruction obligatory for every CHEK2-dependent checkpoint. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:22266820 The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. | KEEP AS NON CORE | Summary: Retain RNF8 ligase binding at substrate-association scope. Reason: The original full source reports CHEK2 association with RNF8 and ubiquitination in supplementary context. This describes interaction with a ubiquitin ligase; CHEK2 is not thereby assigned E3 activity or a direct nonhomologous-end-joining catalytic step. Supporting Evidence: |
| GO:0033554 cellular response to stress | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | UNDECIDED | Summary: The specific stress/autophagy assertion awaits full source-level resolution. Reason: The authentic PMID:37943659 abstract positively reports ATM–CHK2–TRIM32 signaling and ATG7 ubiquitination under oxidative/metabolic stress. Bounded publisher and repository attempts did not recover the full Results/Methods needed to resolve this exact stimulus, assay and species scope. Preserve the experimental assertion; no negative conclusion or removal follows from the access gap. Curated GO-CAM models 654d809000001587 and 654d809000001692 positively place CHEK2 kinase activity in the ATM–CHK2–TRIM32–ATG7 signaling context using PMID:37943659. This is affirmative curated support, not a missing-model claim; it does not provide the inaccessible primary assay details needed to resolve this source-specific judgment. |
| GO:0042176 regulation of protein catabolic process | IMP PMID:17101782 Chk2 mediates stabilization of the FoxM1 transcription facto... | KEEP AS NON CORE | Summary: Retain kinase-dependent regulation of substrate turnover. Reason: Human recombinant CHK2 phosphorylates FOXM1b S361; substrate-mutant and cellular experiments connect this with FOXM1 stabilization. CHEK2 performs the regulatory phosphorylation rather than protein cleavage. This does not resolve the separate contested CDC25A assertion. Supporting Evidence: |
| GO:0042594 response to starvation | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | UNDECIDED | Summary: The specific stress/autophagy assertion awaits full source-level resolution. Reason: The authentic PMID:37943659 abstract positively reports ATM–CHK2–TRIM32 signaling and ATG7 ubiquitination under oxidative/metabolic stress. Bounded publisher and repository attempts did not recover the full Results/Methods needed to resolve this exact stimulus, assay and species scope. Preserve the experimental assertion; no negative conclusion or removal follows from the access gap. Curated GO-CAM models 654d809000001587 and 654d809000001692 positively place CHEK2 kinase activity in the ATM–CHK2–TRIM32–ATG7 signaling context using PMID:37943659. This is affirmative curated support, not a missing-model claim; it does not provide the inaccessible primary assay details needed to resolve this source-specific judgment. |
| GO:0042770 signal transduction in response to DNA damage | IDA PMID:14744935 Endoplasmic reticulum stress induces p53 cytoplasmic localiz... | ACCEPT | Summary: Retain DNA damage-induced signal transduction. Reason: CHEK2 transduces DNA-damage signals through substrate phosphorylation. The full original paper assays CHK2 activation under DNA damage with or without ER stress; the upstream-or-within qualifier is preserved, and a mobility shift is not described as a direct substrate-turnover assay. |
| GO:0042770 signal transduction in response to DNA damage | IMP PMID:11298456 The ATM-Chk2-Cdc25A checkpoint pathway guards against radior... | ACCEPT | Summary: Retain DNA damage-induced signal transduction. Reason: CHEK2 transduces DNA-damage signals through substrate phosphorylation. The original checkpoint source remains positive at signaling scope, while its proposed CDC25A destruction mechanism is separately unresolved. |
| GO:0042802 identical protein binding | IPI PMID:16794575 Trans-activation of the DNA-damage signalling protein kinase... | MODIFY | Summary: Dimerization contributes to CHEK2 activation. Reason: Human CHK2 dimer/activation-loop studies support transient self-association and trans-autophosphorylation. Native full-length behavior is distinguished from GST-driven proximity and isolated kinase-domain crystals; this is not a claim that every active molecule remains an obligate stable dimer. The specific term is already represented by the independent existing IDA row; this refinement preserves each source rather than adding a new annotation. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:18239682 Activation segment dimerization: a mechanism for kinase auto... | MODIFY | Summary: Dimerization contributes to CHEK2 activation. Reason: Human CHK2 dimer/activation-loop studies support transient self-association and trans-autophosphorylation. Native full-length behavior is distinguished from GST-driven proximity and isolated kinase-domain crystals; this is not a claim that every active molecule remains an obligate stable dimer. The specific term is already represented by the independent existing IDA row; this refinement preserves each source rather than adding a new annotation. Proposed replacements: protein homodimerization activity |
| GO:0042803 protein homodimerization activity | IDA PMID:16794575 Trans-activation of the DNA-damage signalling protein kinase... | ACCEPT | Summary: Dimerization contributes to CHEK2 activation. Reason: Human CHK2 dimer/activation-loop studies support transient self-association and trans-autophosphorylation. Native full-length behavior is distinguished from GST-driven proximity and isolated kinase-domain crystals; this is not a claim that every active molecule remains an obligate stable dimer. This original IDA homodimerization assertion is retained. |
| GO:0044773 mitotic DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited mitotic damage-checkpoint role. Reason: The PAINT ancestral assertion is independently consistent with human checkpoint kinase biochemistry. The node history was not reconstructed; neither the short donor list nor the human target among descendants is treated as circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002389572 UNRESOLVED Actual ancestral PAINT assertion preserved; node history was not reconstructed. Target evidence and compartment scope are assessed separately, without donor-count or target-self-reference objections. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:17101782 Chk2 mediates stabilization of the FoxM1 transcription facto... | KEEP AS NON CORE | Summary: Retain positive transcriptional regulation through FOXM1. Reason: Direct FOXM1b phosphorylation and stabilization support increased FOXM1-dependent output in human cells. CHEK2 is the regulatory kinase, not an intrinsic DNA-binding transcription factor or coactivator. Supporting Evidence: |
| GO:0046777 protein autophosphorylation | IDA PMID:16794575 Trans-activation of the DNA-damage signalling protein kinase... | ACCEPT | Summary: Autophosphorylation is integral to CHEK2 activation and signaling. Reason: Human kinase experiments distinguish activation-loop trans-autophosphorylation from S379-dependent signaling/ubiquitination effects. Retain the source-specific site and construct context without assigning the same phosphorylation or activity to every alternative product. |
| GO:0046777 protein autophosphorylation | IDA PMID:18644861 Regulation of Chk2 ubiquitination and signaling through auto... | ACCEPT | Summary: Autophosphorylation is integral to CHEK2 activation and signaling. Reason: Human kinase experiments distinguish activation-loop trans-autophosphorylation from S379-dependent signaling/ubiquitination effects. Retain the source-specific site and construct context without assigning the same phosphorylation or activity to every alternative product. |
| GO:0050821 protein stabilization | IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage. | KEEP AS NON CORE | Summary: Retain E2F1 stabilization as a substrate-regulatory output. Reason: The original abstract and author thesis show kinase-site-dependent E2F1 stability in human-cell cycloheximide experiments. This is a supported substrate effect, not a claim that CHEK2 stabilizes all proteins. Supporting Evidence: PMID:12717439 protein stabilization, increased half-life |
| GO:0050821 protein stabilization | IDA PMID:18833288 ATM and Chk2 kinase target the p53 cofactor Strap. | KEEP AS NON CORE | Summary: Retain STRAP stabilization downstream of phosphorylation. Reason: Original selected Results report recombinant CHK2 phosphorylation of STRAP S221 and human-cell stability experiments. ATM-dependent nuclear accumulation and CHK2-dependent stabilization are distinct steps; no universal protein-protection activity is implied. Supporting Evidence: |
| GO:0090307 mitotic spindle assembly | IMP PMID:20364141 The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal... | MODIFY | Summary: Specify regulation of mitotic spindle assembly. Reason: Human CHK2 perturbation, BRCA1 S988 phosphorylation measured by mass spectrometry, and S988E rescue support a performed regulatory pathway. The paper’s purified kinase assay uses CDC25C, not purified BRCA1. Spindle-assembly checkpoint function remains intact, so neither a spindle motor nor checkpoint-signaling defect is inferred. Proposed replacements: regulation of mitotic spindle assembly Supporting Evidence: PMID:20364141 identified Brca1 as a mitotic target |
| GO:0090399 replicative senescence | NAS PMID:15149599 Telomere shortening triggers senescence of human cells throu... | UNDECIDED | Summary: The exact source-specific replicative-senescence role remains unresolved. Reason: The original abstract describes senescent human fibroblasts and ATM/p53 signaling but does not resolve the CHK2-specific experiment. The full body was not recovered. This preserves the NAS assertion pending source inspection, without treating the paper’s focus on other pathway proteins as evidence of a wrong gene. Supporting Evidence: |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Retain serine-directed kinase activity within the broader Ser/Thr specificity. Reason: Direct human CHK2 phosphorylation of serine substrates corroborates this activity. The Rhea mapping and the TRIM32-report source remain intact; an abstract-limited TRIM32 assay is not used to infer an additional catalytic class or to exclude threonine substrates. |
| GO:0106310 protein serine kinase activity | IMP PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: Retain serine-directed kinase activity within the broader Ser/Thr specificity. Reason: Direct human CHK2 phosphorylation of serine substrates corroborates this activity. The Rhea mapping and the TRIM32-report source remain intact; an abstract-limited TRIM32 assay is not used to infer an additional catalytic class or to exclude threonine substrates. |
| GO:1901796 regulation of signal transduction by p53 class mediator | TAS Reactome:R-HSA-6804756 | ACCEPT | Summary: Retain regulation of p53-mediated signaling through phosphorylation. Reason: The exact Reactome branch links CHEK2 substrate phosphorylation to p53 regulation. Its methylation or degradation context does not assign methyltransferase or protease activity to CHEK2; the performed role is regulatory phosphorylation. Supporting Evidence: Reactome:R-HSA-6804756 Reactome:R-HSA-69685 Reactome:R-HSA-349426 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:1901796 regulation of signal transduction by p53 class mediator | TAS Reactome:R-HSA-6804760 | ACCEPT | Summary: Retain regulation of p53-mediated signaling through phosphorylation. Reason: The exact Reactome branch links CHEK2 substrate phosphorylation to p53 regulation. Its methylation or degradation context does not assign methyltransferase or protease activity to CHEK2; the performed role is regulatory phosphorylation. Supporting Evidence: Reactome:R-HSA-6804760 Reactome:R-HSA-69685 Reactome:R-HSA-349426 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:1901796 regulation of signal transduction by p53 class mediator | TAS Reactome:R-HSA-6806003 | ACCEPT | Summary: Retain regulation of p53-mediated signaling through phosphorylation. Reason: The exact Reactome branch links CHEK2 substrate phosphorylation to p53 regulation. Its methylation or degradation context does not assign methyltransferase or protease activity to CHEK2; the performed role is regulatory phosphorylation. Supporting Evidence: Reactome:R-HSA-6806003 Reactome:R-HSA-69685 Reactome:R-HSA-349426 file:human/CHEK2/CHEK2-source-evidence.json |
| GO:2000785 regulation of autophagosome assembly | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | UNDECIDED | Summary: The specific stress/autophagy assertion awaits full source-level resolution. Reason: The authentic PMID:37943659 abstract positively reports ATM–CHK2–TRIM32 signaling and ATG7 ubiquitination under oxidative/metabolic stress. Bounded publisher and repository attempts did not recover the full Results/Methods needed to resolve this exact stimulus, assay and species scope. Preserve the experimental assertion; no negative conclusion or removal follows from the access gap. Curated GO-CAM models 654d809000001587 and 654d809000001692 positively place CHEK2 kinase activity in the ATM–CHK2–TRIM32–ATG7 signaling context using PMID:37943659. This is affirmative curated support, not a missing-model claim; it does not provide the inaccessible primary assay details needed to resolve this source-specific judgment. |
| GO:2000786 positive regulation of autophagosome assembly | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | UNDECIDED | Summary: The specific stress/autophagy assertion awaits full source-level resolution. Reason: The authentic PMID:37943659 abstract positively reports ATM–CHK2–TRIM32 signaling and ATG7 ubiquitination under oxidative/metabolic stress. Bounded publisher and repository attempts did not recover the full Results/Methods needed to resolve this exact stimulus, assay and species scope. Preserve the experimental assertion; no negative conclusion or removal follows from the access gap. Curated GO-CAM models 654d809000001587 and 654d809000001692 positively place CHEK2 kinase activity in the ATM–CHK2–TRIM32–ATG7 signaling context using PMID:37943659. This is affirmative curated support, not a missing-model claim; it does not provide the inaccessible primary assay details needed to resolve this source-specific judgment. |
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Download this section (compressed HTML)Q: Which CHEK2 products retain specific substrates, activation modes and compartment-specific functions in native human cells, particularly the partially active del2–3 product?
Q: Under which cell and damage conditions does CHEK2 contribute to CDC25A destruction, given the CHK1/Ser76-dependent pathway and retained turnover in CHK2-null HCT116 cells?
Q: Can the exact CARF and TNKS1BP1 interaction records and the cytoplasmic active-pool assertion be resolved independently of downstream CHK2 phosphorylation readouts?
Experiment: Compare sequence-verified CHEK2 alternative products at endogenous abundance using matched substrate-phosphorylation and localization measurements, including a displayed-product control and kinase-dead controls.
Experiment: Combine acute CHK2 depletion with CHK1 perturbation and CDC25A site-specific mutants in matched damage contexts, measuring phosphorylation, ubiquitination and turnover separately.
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