CHEK1 (checkpoint kinase 1, Chk1) is a nuclear serine/threonine-protein kinase (EC 2.7.11.1) of the CAMK group and the principal effector kinase of the ATR-dependent DNA replication-stress and DNA-damage checkpoints. It has an N-terminal catalytic domain and a C-terminal autoinhibitory regulatory region; the isolated kinase domain is markedly more active than the full-length protein. Activated by ATR phosphorylation at Ser317 and Ser345 (with Claspin/CLSPN as mediator and BRCA1 and FEM1B as modulators) followed by Ser296 autophosphorylation, Chk1 restrains cyclin-dependent kinase activity to enforce the intra-S and G2/M checkpoints. Its central outputs are phosphorylation of the CDC25 phosphatases (targeting CDC25A for degradation and creating a 14-3-3 docking site on CDC25C Ser216) and stabilization of WEE1 (indirectly, via phosphorylation of PABIR1/FAM122A and activation of PP2A-B55alpha), which together suppress CDK1/CDK2 activity, limit replication-origin firing, and protect stalled replication forks. Chk1 additionally phosphorylates substrates that coordinate homologous-recombination repair (RAD51 Thr309), the Fanconi anemia/BRCA cross-link pathway (FANCE), the p53 network (p53, MDMX), chromatin/transcription (histone H3 Thr11; TLK1), mitotic fidelity (Aurora B Ser331, NEK6, NEK11) and other targets. It is predominantly nuclear but shuttles to the cytoplasm and localizes to interphase centrosomes, where it shields centrosomal CDK1 from premature activation by CDC25B. Chk1 is an Hsp90/Cdc37 client, and activated Chk1 is turned over by SCF(FBXO6)-mediated ubiquitination to terminate the checkpoint. The gene is essential; complete loss causes early embryonic lethality.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000077 DNA damage checkpoint signaling | IDA PMID:12660173 Human Tousled like kinases are targeted by an ATM- and Chk1-... | ACCEPT | Summary: CHK1 acts in the DNA-damage checkpoint by phosphorylating checkpoint substrates such as TLK1. Reason: IDA for DNA damage checkpoint signaling; CHK1 is the effector kinase of this pathway. Core function. Supporting Evidence: PMID:12660173 Chk1 phosphorylates Tlk1 on serine 695 (S695) in vitro |
| GO:0000077 DNA damage checkpoint signaling | IDA PMID:16963448 Repeated phosphopeptide motifs in human Claspin are phosphor... | ACCEPT | Summary: CHK1 is the ATR-activated effector of DNA-damage checkpoint signaling; here via Claspin phosphorylation. Reason: IDA well supported; core checkpoint-signaling function. Supporting Evidence: PMID:16963448 Thr-916 on Claspin is phosphorylated by Chk1 |
| GO:0000077 DNA damage checkpoint signaling | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based IEA for DNA damage checkpoint signaling, consistent with CHK1 core function. Reason: IEA from the Chk1 catalytic-domain InterPro signature; correct and consistent with experimental evidence. |
| GO:0000077 DNA damage checkpoint signaling | IMP PMID:19716789 The F box protein Fbx6 regulates Chk1 stability and cellular... | ACCEPT | Summary: CHK1 stability/turnover experiments (Fbx6) place it in DNA-damage checkpoint signaling. Reason: IMP consistent with CHK1 as the checkpoint effector kinase; core function. Supporting Evidence: PMID:19716789 an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 |
| GO:0000781 chromosome, telomeric region | IDA PMID:15149599 Telomere shortening triggers senescence of human cells throu... | KEEP AS NON CORE | Summary: Colocalizes with the telomeric region in senescent cells; a context-specific localization. Reason: Telomere-associated DNA-damage foci form in senescence; peripheral to CHK1 core checkpoint-kinase role and not fully resolvable from the cached abstract. Supporting Evidence: PMID:15149599 Telomeric foci containing multiple DNA damage response factors were assembled in a subset of senescent cells |
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin localization (IEA from mouse ortholog), consistent with chromatin-associated CHK1. Reason: CHK1 associates with chromatin in cycling cells; IEA is appropriate. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0000785 chromatin | ISS GO_REF:0000024 | ACCEPT | Summary: Chromatin localization by ISS from mouse ortholog; consistent with chromatin-associated CHK1. Reason: Supported by experimental chromatin association of human CHK1. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0000794 condensed nuclear chromosome | IDA PMID:9382850 Atm-dependent interactions of a mammalian chk1 homolog with ... | KEEP AS NON CORE | Summary: CHK1 localizes along condensed meiotic chromosomes in spermatocytes. Reason: Genuine but context-specific (meiotic) localization; peripheral to the somatic checkpoint-kinase core. Supporting Evidence: PMID:9382850 Chk1 accumulates in late zygotene and pachytene spermatocytes and is present along synapsed meiotic chromosomes |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein kinase activity (IEA); CHK1 is a bona fide protein kinase. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Broad parent term, correct. |
| GO:0004672 protein kinase activity | IMP PMID:22024163 Phosphorylation at serine 331 is required for Aurora B activ... | ACCEPT | Summary: Kinase activity inferred from Aurora B Ser331 phosphorylation by CHK1. Reason: IMP; CHK1 kinase activity is well established. Supporting Evidence: PMID:22024163 Chk1 in vitro kinase assay |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16963448 Repeated phosphopeptide motifs in human Claspin are phosphor... | ACCEPT | Summary: Protein serine/threonine kinase activity, the core molecular function of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Supporting Evidence: PMID:16963448 Thr-916 on Claspin is phosphorylated by Chk1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:9278511 Conservation of the Chk1 checkpoint pathway in mammals: link... | ACCEPT | Summary: CHK1 phosphorylates CDC25 phosphatases on Ser/Thr; defining catalytic activity. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Supporting Evidence: PMID:9278511 Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ser/Thr kinase activity (IEA, EC 2.7.11.1); consistent with all experimental evidence. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5685230 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5685242 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-6799246 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-69604 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-75010 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9007539 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9943662 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9943678 | ACCEPT | Summary: Protein serine/threonine kinase activity (Reactome TAS) for CHK1 checkpoint phosphorylation events. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. Reactome models CHK1-catalyzed phosphorylation of CDC25A, TP53, RAD51, BRCA2, E2F6, NEK11. |
| GO:0005515 protein binding | IPI PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinas... | REMOVE | Summary: Generic protein binding to CDC25C. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. CDC25C is a CHK1 substrate; substrate binding is implied by the kinase activity. Supporting Evidence: PMID:11836499 BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest |
| GO:0005515 protein binding | IPI PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinas... | REMOVE | Summary: Generic protein binding to BRCA1. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. BRCA1 is an upstream activator of CHK1; interaction is regulatory, not a distinct MF. Supporting Evidence: PMID:11836499 BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest |
| GO:0005515 protein binding | IPI PMID:15665856 The cell-cycle checkpoint kinase Chk1 is required for mammal... | REMOVE | Summary: Generic protein binding to RAD51. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. RAD51 is a CHK1 substrate (Thr309); substrate binding implied by kinase activity. Supporting Evidence: PMID:15665856 RAD51 is phosphorylated on Thr 309 in a Chk1-dependent manner |
| GO:0005515 protein binding | IPI PMID:15798197 Coupling of human circadian and cell cycles by the timeless ... | REMOVE | Summary: Generic protein binding to TIMELESS. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. TIMELESS is a checkpoint scaffold/regulator interacting with CHK1. Supporting Evidence: PMID:15798197 human Timeless protein interacts with both the circadian clock protein cryptochrome 2 and with the cell cycle checkpoint proteins Chk1 |
| GO:0005515 protein binding | IPI PMID:16330544 Chaperoning checkpoint kinase 1 (Chk1), an Hsp90 client, wit... | MODIFY | Summary: CHK1 is an Hsp90/Cdc37 chaperone client. Reason: Resolve generic protein binding to the informative MF Hsp90 protein binding; CHK1 is an established Hsp90 client. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:16330544 is destabilized when heat shock protein 90 (Hsp90) is inhibited, suggesting that Chk1 is an Hsp90 client |
| GO:0005515 protein binding | IPI PMID:16330544 Chaperoning checkpoint kinase 1 (Chk1), an Hsp90 client, wit... | REMOVE | Summary: Generic protein binding to CDC25C. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. CDC25C is a CHK1 substrate; substrate binding implied by kinase activity. Supporting Evidence: PMID:9278511 Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C |
| GO:0005515 protein binding | IPI PMID:16511572 14-3-3gamma binds to MDMX that is phosphorylated by UV-activ... | REMOVE | Summary: Generic protein binding to TP53. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. TP53 is a CHK1 substrate; interaction captured by kinase activity on p53. Supporting Evidence: PMID:10673501 recombinant hCHK1, but not a kinase-defective version of hCHK1, can phosphorylate p53 in vitro at S20 |
| GO:0005515 protein binding | IPI PMID:16963448 Repeated phosphopeptide motifs in human Claspin are phosphor... | REMOVE | Summary: Generic protein binding to CLSPN. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. Claspin is the CHK1-activation mediator and a CHK1 substrate. Supporting Evidence: PMID:16963448 Thr-916 on Claspin is phosphorylated by Chk1 |
| GO:0005515 protein binding | IPI PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple... | REMOVE | Summary: Generic protein binding to RB1. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. RB1 is phosphorylated by CHK1 (Ser612); substrate binding implied by kinase activity. Supporting Evidence: PMID:17380128 the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage |
| GO:0005515 protein binding | IPI PMID:19223857 Tumor suppressor protein C53 antagonizes checkpoint kinases ... | REMOVE | Summary: Generic protein binding to CDK5RAP3 (C53/LZAP). Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. C53 antagonizes CHK1; regulatory interaction, no distinct MF term. Supporting Evidence: PMID:19223857 C53 interacts with Chk1 and antagonizes its function |
| GO:0005515 protein binding | IPI PMID:19330022 Human FEM1B is required for Rad9 recruitment and CHK1 activa... | REMOVE | Summary: Generic protein binding to FEM1B. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. FEM1B is a CHK1-activation adaptor; regulatory interaction. Supporting Evidence: PMID:19330022 FEM1B ... is involved in the activation of CHK1 |
| GO:0005515 protein binding | IPI PMID:19716789 The F box protein Fbx6 regulates Chk1 stability and cellular... | REMOVE | Summary: Generic protein binding to FBXO6. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. FBXO6 (SCF) targets activated CHK1 for degradation; regulatory interaction. Supporting Evidence: PMID:19716789 an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 |
| GO:0005515 protein binding | IPI PMID:20639859 14-3-3gamma mediates Cdc25A proteolysis to block premature m... | MODIFY | Summary: Phospho-CHK1 (Ser296) is bound by 14-3-3 proteins that regulate its localization/activity. Reason: Resolve generic protein binding to the informative MF 14-3-3 protein binding; a genuine, literature-supported regulatory interaction. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:20639859 14-3-3Ξ³ forms a complex with Chk1 phosphorylated at Ser296 |
| GO:0005515 protein binding | IPI PMID:20639859 14-3-3gamma mediates Cdc25A proteolysis to block premature m... | MODIFY | Summary: Phospho-CHK1 (Ser296) is bound by 14-3-3 proteins that regulate its localization/activity. Reason: Resolve generic protein binding to the informative MF 14-3-3 protein binding; a genuine, literature-supported regulatory interaction. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:20639859 14-3-3Ξ³ forms a complex with Chk1 phosphorylated at Ser296 |
| GO:0005515 protein binding | IPI PMID:22505024 Chk1 phosphorylates the tumour suppressor Mig-6, regulating ... | REMOVE | Summary: Generic protein binding to ERRFI1 (Mig-6). Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. Mig-6 is a CHK1 substrate (Ser251); substrate binding implied by kinase activity. Supporting Evidence: PMID:22505024 S251 and S302, but not S273, S276, or S326, were phosphorylated by Chk1 in vitro |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | MODIFY | Summary: CHK1 is an Hsp90/Cdc37 chaperone client. Reason: Resolve generic protein binding to the informative MF Hsp90 protein binding; CHK1 is an established Hsp90 client. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:22939624 CDC37 provides recognition of the kinase family |
| GO:0005515 protein binding | IPI PMID:25249323 ATR/Chk1/Smurf1 pathway determines cell fate after DNA damag... | REMOVE | Summary: Generic protein binding to SMURF1. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. Smurf1 is phosphorylated by CHK1; substrate binding implied by kinase activity. Supporting Evidence: PMID:25249323 phosphorylation of Smurf1 that enhances its self-degradation |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding to HLA-DRB5. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. High-throughput (BioPlex) interactome hit; no functional relevance for a nuclear checkpoint kinase. Supporting Evidence: PMID:28514442 networks of protein-protein interactions |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding to HLA-DRB5. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. High-throughput (BioPlex) interactome hit; no functional relevance for a nuclear checkpoint kinase. Supporting Evidence: PMID:33961781 cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Phospho-CHK1 (Ser296) is bound by 14-3-3 proteins that regulate its localization/activity. Reason: Resolve generic protein binding to the informative MF 14-3-3 protein binding; a genuine, literature-supported regulatory interaction. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:35271311 systematically map the localization and interactions of human proteins |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Generic protein binding to TP53. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. High-throughput neo-PPI screen; TP53 is in any case a CHK1 substrate. Supporting Evidence: PMID:35512704 mutation-directed neo-protein-protein interactions in cancer |
| GO:0005515 protein binding | IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot... | REMOVE | Summary: Generic protein binding to HRAS. Reason: Generic protein binding (GO:0005515) is uninformative as a molecular function; removal does not assert the interaction is false. High-throughput RAS-interactome hit; not an established functional CHK1 interaction. Supporting Evidence: PMID:35839996 HRAS-specific CARM1 and CHK1 |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Phospho-CHK1 (Ser296) is bound by 14-3-3 proteins that regulate its localization/activity. Reason: Resolve generic protein binding to the informative MF 14-3-3 protein binding; a genuine, literature-supported regulatory interaction. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:36931259 14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Phospho-CHK1 (Ser296) is bound by 14-3-3 proteins that regulate its localization/activity. Reason: Resolve generic protein binding to the informative MF 14-3-3 protein binding; a genuine, literature-supported regulatory interaction. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:40205054 joint measurement of biophysical interactions |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding, required for CHK1 phosphotransfer catalysis. Reason: IEA from kinase InterPro signatures; CHK1 binds ATP in its catalytic cleft. Correct and consistent with kinase activity. |
| GO:0005576 extracellular region | HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter... | REMOVE | Summary: Extracellular detection in a shotgun proteomics survey of glaucoma tears. Reason: HDA biofluid proteomics (tears); CHK1 is a nuclear checkpoint kinase, not an extracellular protein. This detection does not reflect a site of function. Supporting Evidence: PMID:23580065 shotgun proteomics approach to tears of patients with POAG |
| GO:0005634 nucleus | EXP PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinas... | ACCEPT | Summary: Nuclear localization (EXP); the nucleus is the principal site of CHK1 function. Reason: CHK1 is predominantly nuclear; core location. |
| GO:0005634 nucleus | EXP PMID:12676962 Regulation of Chk1 includes chromatin association and 14-3-3... | ACCEPT | Summary: Nuclear localization (EXP); the nucleus is the principal site of CHK1 function. Reason: CHK1 is predominantly nuclear; core location. |
| GO:0005634 nucleus | EXP PMID:15710331 Lack of PTEN sequesters CHK1 and initiates genetic instabili... | ACCEPT | Summary: Nuclear localization (EXP); the nucleus is the principal site of CHK1 function. Reason: CHK1 is predominantly nuclear; core location. |
| GO:0005634 nucleus | EXP PMID:9278511 Conservation of the Chk1 checkpoint pathway in mammals: link... | ACCEPT | Summary: Nuclear localization (EXP); the nucleus is the principal site of CHK1 function. Reason: CHK1 is predominantly nuclear; core location. |
| GO:0005634 nucleus | IDA PMID:15311285 Centrosome-associated Chk1 prevents premature activation of ... | ACCEPT | Summary: Nuclear localization (IDA). Reason: Core CHK1 location. |
| GO:0005634 nucleus | IDA PMID:20932473 DNA damage activates a spatially distinct late cytoplasmic c... | ACCEPT | Summary: Nuclear localization (IDA, MK2 checkpoint study). Reason: Nuclear CHK1 activity establishes the G2/M checkpoint. Supporting Evidence: PMID:20932473 nuclear Chk1 activity is essential to establish a G(2)/M checkpoint |
| GO:0005634 nucleus | IDA PMID:26296656 hHR23A is required to control the basal turnover of Chk1. | ACCEPT | Summary: Nuclear localization (IDA). Reason: Core CHK1 location. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization (IEA, subcellular-location mapping). Reason: Consistent with experimental nuclear localization. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176116 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685230 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685242 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799246 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69604 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75010 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9007539 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9943662 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9943678 | ACCEPT | Summary: Nucleoplasm localization (IDA/Reactome TAS). Reason: CHK1 acts in the nucleoplasm; consistent with its nuclear checkpoint role. |
| GO:0005657 replication fork | IEA GO_REF:0000107 | ACCEPT | Summary: Replication fork localization (IEA from mouse ortholog). Reason: CHK1 acts at stalled/active replication forks in the intra-S checkpoint; consistent with chromatin association. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0005694 chromosome | EXP PMID:12676962 Regulation of Chk1 includes chromatin association and 14-3-3... | ACCEPT | Summary: Chromosome/chromatin localization (EXP). Reason: CHK1 is chromatin-associated; consistent location. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0005694 chromosome | EXP PMID:31316063 SPRTN protease and checkpoint kinase 1 cross-activation loop... | ACCEPT | Summary: Chromosome/chromatin localization (EXP). Reason: CHK1 is chromatin-associated; consistent location. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0005694 chromosome | EXP PMID:9382850 Atm-dependent interactions of a mammalian chk1 homolog with ... | ACCEPT | Summary: Chromosome/chromatin localization (EXP). Reason: CHK1 is chromatin-associated; consistent location. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Chromosome localization (IEA). Reason: Consistent with experimental chromatin association. |
| GO:0005737 cytoplasm | EXP PMID:12676962 Regulation of Chk1 includes chromatin association and 14-3-3... | ACCEPT | Summary: Cytoplasmic localization (EXP); CHK1 shuttles between nucleus and cytoplasm. Reason: CHK1 undergoes CRM1/XPO1-dependent nuclear export; cytoplasmic pool is real. Supporting Evidence: PMID:12676962 Chk1 is associated with chromatin in cycling cells |
| GO:0005737 cytoplasm | IDA PMID:26296656 hHR23A is required to control the basal turnover of Chk1. | ACCEPT | Summary: Cytoplasmic localization (IDA). Reason: CHK1 shuttles to the cytoplasm; consistent location. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization (IEA). Reason: Consistent with nucleocytoplasmic shuttling of CHK1. |
| GO:0005813 centrosome | IDA PMID:15311285 Centrosome-associated Chk1 prevents premature activation of ... | ACCEPT | Summary: Interphase centrosome localization (IDA); centrosomal CHK1 shields CDK1 from premature activation. Reason: Well documented; core aspect of CHK1 control of mitotic timing. Supporting Evidence: PMID:15311285 human Chk1 kinase localizes to interphase, but not mitotic, centrosomes |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Centrosome localization (IEA). Reason: Consistent with experimental centrosomal CHK1. Supporting Evidence: PMID:15311285 human Chk1 kinase localizes to interphase, but not mitotic, centrosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205328 | REMOVE | Summary: Cytosol localization derived from Reactome R-HSA-205328. Reason: R-HSA-205328 ("Interaction of other tyrosine kinases with p-KIT") explicitly concerns "CHK1 (Csk homologous kinase or MATK)", a cytoplasmic tyrosine kinase, NOT CHEK1/Chk1 checkpoint kinase. This is a gene-name collision; the annotation is mis-attributed to the wrong protein. Supporting Evidence: Reactome:R-HSA-205328 CHK1 (Csk homologous kinase or MATK), FER and FES associate with p-KIT |
| GO:0006260 DNA replication | TAS Reactome:R-HSA-176187 | MODIFY | Summary: CHK1 restrains DNA replication (origin firing, fork progression) but does not perform replication. Reason: GO:0006260 (DNA replication) implies the replication process itself; CHK1 regulates it. Reactome models CHK1 in ATR-dependent reduction of origin firing. Proposed replacements: regulation of DNA replication Supporting Evidence: Reactome:R-HSA-176187 reduction of replication origin firing |
| GO:0006281 DNA repair | IMP PMID:19716789 The F box protein Fbx6 regulates Chk1 stability and cellular... | KEEP AS NON CORE | Summary: CHK1 is required for efficient DNA repair (HRR) after replication stress. Reason: IMP for DNA repair (broad term). CHK1 regulates rather than executes repair; retain as a genuine but non-core, downstream role. Supporting Evidence: PMID:15665856 Chk1 is a key regulator of genome maintenance by the homologous recombination repair (HRR) system |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chromatin remodeling (IEA) linked to CHK1 histone H3T11 phosphorylation / transcriptional repression. Reason: CHK1 modulates chromatin-templated transcription via H3T11ph; "chromatin remodeling" is a broad, downstream framing. Non-core. Supporting Evidence: PMID:18243098 H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo |
| GO:0006338 chromatin remodeling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chromatin remodeling (ISS from mouse ortholog). Reason: Same downstream H3T11-linked role; non-core. Supporting Evidence: PMID:18243098 H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo |
| GO:0006974 DNA damage response | IMP PMID:20932473 DNA damage activates a spatially distinct late cytoplasmic c... | ACCEPT | Summary: CHK1 is central to the DNA damage response (IMP). Reason: Broad but correct; CHK1 is a core DDR effector. Supporting Evidence: PMID:20932473 nuclear Chk1 activity is essential to establish a G(2)/M checkpoint |
| GO:0006974 DNA damage response | ISS GO_REF:0000024 | ACCEPT | Summary: DNA damage response (ISS from mouse ortholog). Reason: Consistent with core DDR role. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: IBA places CHK1 in mitotic G2 DNA damage checkpoint signaling, its core process. Reason: PAINT node PTN002388913 infers the G2 DNA-damage checkpoint; CHK1 itself is among the descendant evidences (correct, not circular). Core function. Supporting Evidence: file:human/CHEK1/CHEK1-deep-research-falcon.md Its primary function is to phosphorylate proteins that restrain cyclin-dependent kinase activity, suppress inappropriate replication-origin firing, stabilize or protect stressed replication forks, coordinate homologous recombination |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:20932473 DNA damage activates a spatially distinct late cytoplasmic c... | ACCEPT | Summary: Nuclear CHK1 establishes the mitotic G2 DNA-damage checkpoint (IMP). Reason: Core checkpoint function. Supporting Evidence: PMID:20932473 nuclear Chk1 activity is essential to establish a G(2)/M checkpoint |
| GO:0010569 regulation of double-strand break repair via homologous recombination | IDA PMID:15665856 The cell-cycle checkpoint kinase Chk1 is required for mammal... | ACCEPT | Summary: CHK1 regulates DSB repair via homologous recombination by phosphorylating RAD51 (Thr309). Reason: Direct, specific role: CHK1 promotes RAD51-dependent HRR. Well supported. Supporting Evidence: PMID:15665856 RAD51 is phosphorylated on Thr 309 in a Chk1-dependent manner PMID:15665856 Chk1 is a key regulator of genome maintenance by the homologous recombination repair (HRR) system |
| GO:0019904 protein domain specific binding | IPI PMID:26296656 hHR23A is required to control the basal turnover of Chk1. | KEEP AS NON CORE | Summary: Domain-specific binding to the hHR23A/RAD23A UBA domains, regulating CHK1 turnover. Reason: A more informative term than generic protein binding; reflects regulation of CHK1 basal turnover. Non-core. Supporting Evidence: PMID:26296656 hHR23A associates with Chk1 through its UBA domains |
| GO:0032991 protein-containing complex | IDA PMID:26296656 hHR23A is required to control the basal turnover of Chk1. | REMOVE | Summary: Membership in an unspecified protein-containing complex (hHR23A study). Reason: GO:0032991 is the root complex term and is uninformative; CHK1 acts as a largely monomeric kinase with transient interactions rather than as a defined stable complex subunit. Removal does not assert the interaction is false. Supporting Evidence: PMID:26296656 hHR23A associates with Chk1 through its UBA domains |
| GO:0035402 histone H3T11 kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Histone H3T11 kinase activity (IBA). Reason: PAINT-inferred, supported by direct human/mouse evidence; a genuine specific MF. Supporting Evidence: PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression |
| GO:0035402 histone H3T11 kinase activity | IDA PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA ... | ACCEPT | Summary: CHK1 phosphorylates histone H3 on Thr11 (IDA). Reason: Direct experimental demonstration. Supporting Evidence: PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression |
| GO:0035402 histone H3T11 kinase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Histone H3T11 kinase activity (IEA from mouse ortholog). Reason: Consistent with human IDA evidence. Supporting Evidence: PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression |
| GO:0042770 signal transduction in response to DNA damage | IDA PMID:16963448 Repeated phosphopeptide motifs in human Claspin are phosphor... | ACCEPT | Summary: Signal transduction in response to DNA damage (IDA) via Claspin. Reason: CHK1 is a core DNA-damage signal transducer. Supporting Evidence: PMID:16963448 Thr-916 on Claspin is phosphorylated by Chk1 |
| GO:0042770 signal transduction in response to DNA damage | IEA GO_REF:0000117 | ACCEPT | Summary: Signal transduction in response to DNA damage (IEA/ARBA). Reason: Consistent with core CHK1 signaling role. |
| GO:0044818 mitotic G2/M transition checkpoint | IDA PMID:9278511 Conservation of the Chk1 checkpoint pathway in mammals: link... | ACCEPT | Summary: CHK1 enforces the mitotic G2/M transition checkpoint by inhibiting CDC25. Reason: Core function; CHK1 phosphorylates CDC25C Ser216 to block CDK1 activation. Modeled in gocams/653b0ce600000623 and modules/g2_m_transition.yaml. Supporting Evidence: PMID:9278511 Chk1 phosphorylates Cdc25C on serine-216 |
| GO:0044818 mitotic G2/M transition checkpoint | IMP PMID:33108758 CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promote... | ACCEPT | Summary: G2/M transition checkpoint via CHK1-FAM122A-PP2A-WEE1 axis (IMP with CHK1 inhibitor). Reason: Core checkpoint function; CHK1 phosphorylates FAM122A to stabilize WEE1 and activate the G2/M checkpoint. Supporting Evidence: PMID:33108758 CHK1 directly phosphorylated FAM122A on a highly conserved site, Ser37 PMID:33108758 CHK1 is known to directly phosphorylate WEE1 thereby activating a G2/M checkpoint |
| GO:0045787 positive regulation of cell cycle | IDA PMID:26296656 hHR23A is required to control the basal turnover of Chk1. | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell cycle (IDA) from an hHR23A/CHK1-turnover study. Reason: CHK1 is fundamentally a checkpoint/negative regulator; the cited paper concerns hHR23A control of Chk1 protein turnover, not a positive cell-cycle-driving activity. Over-annotation. Supporting Evidence: PMID:26296656 hHR23A acts as a carrier to promote Chk1 degradation through the Ubiquitin Proteasome System |
| GO:0045814 negative regulation of gene expression, epigenetic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epigenetic negative regulation of gene expression via H3T11 phosphorylation. Reason: Genuine but downstream/context-specific transcriptional-repression role; non-core relative to checkpoint-kinase action. Supporting Evidence: PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression |
| GO:0045814 negative regulation of gene expression, epigenetic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Epigenetic negative regulation of gene expression (ISS). Reason: Same H3T11-linked role; non-core. Supporting Evidence: PMID:18243098 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression |
| GO:0045839 negative regulation of mitotic nuclear division | IDA PMID:15311285 Centrosome-associated Chk1 prevents premature activation of ... | ACCEPT | Summary: Centrosomal CHK1 negatively regulates mitotic nuclear division by preventing premature CDK1 activation. Reason: Direct evidence: forced/active centrosomal CHK1 blocks centrosomal CDK1 activation and premature mitosis. Supporting Evidence: PMID:15311285 wild-type Chk1 impaired activation of centrosome-associated Cdk1, thereby resulting in DNA endoreplication and centrosome amplification |
| GO:0046602 regulation of mitotic centrosome separation | IDA PMID:15311285 Centrosome-associated Chk1 prevents premature activation of ... | ACCEPT | Summary: CHK1 regulates mitotic centrosome separation; its inhibition causes premature separation. Reason: Direct IDA; centrosome-associated CHK1 restrains premature centrosome separation. Supporting Evidence: PMID:15311285 Chemical inhibition of Chk1 resulted in premature centrosome separation |
| GO:0070317 negative regulation of G0 to G1 transition | TAS Reactome:R-HSA-8953750 | KEEP AS NON CORE | Summary: Negative regulation of G0-to-G1 transition (Reactome, via E2F6 phosphorylation). Reason: CHK1 phosphorylates E2F6 during replication stress to modulate E2F-target transcription; a downstream, context-specific role. Non-core. Supporting Evidence: Reactome:R-HSA-9007539 CHEK1-mediated phosphorylation prevents association of E2F6 with its target promoters |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | MARK AS OVER ANNOTATED | Summary: Cellular response to mechanical stimulus (IEP) from a BAD/prostate-cancer study. Reason: IEP (expression-pattern) evidence; the cited paper concerns BAD in prostate cancer and does not establish a mechanical-stimulus response role for CHK1. Peripheral over-annotation. Supporting Evidence: PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer growth |
| GO:0090399 replicative senescence | NAS PMID:15149599 Telomere shortening triggers senescence of human cells throu... | KEEP AS NON CORE | Summary: Replicative senescence (NAS) associated with telomeric DNA-damage signaling. Reason: CHK1 participates in checkpoint signaling that can contribute to senescence; NAS and peripheral to the core checkpoint-kinase function. Supporting Evidence: PMID:15149599 Telomeric foci containing multiple DNA damage response factors were assembled in a subset of senescent cells |
| GO:0106310 protein serine kinase activity | EXP PMID:10673501 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:12660173 Human Tousled like kinases are targeted by an ATM- and Chk1-... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:14559997 Chk1 kinase negatively regulates mitotic function of Cdc25A ... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:15659650 p53 C-terminal phosphorylation by CHK1 and CHK2 participates... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:15665856 The cell-cycle checkpoint kinase Chk1 is required for mammal... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:16511572 14-3-3gamma binds to MDMX that is phosphorylated by UV-activ... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:16963448 Repeated phosphopeptide motifs in human Claspin are phosphor... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:17296736 Chk1-mediated phosphorylation of FANCE is required for the F... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:18317453 The checkpoint kinases Chk1 and Chk2 regulate the functional... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:18728393 Nek6 is involved in G2/M phase cell cycle arrest through DNA... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:31316063 SPRTN protease and checkpoint kinase 1 cross-activation loop... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | EXP PMID:9278511 Conservation of the Chk1 checkpoint pathway in mammals: link... | ACCEPT | Summary: Protein serine kinase activity (EXP); the core catalytic activity of CHK1. Reason: CHK1 is a serine/threonine-protein kinase (EC 2.7.11.1); catalytic kinase activity is its defining, core molecular function. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity (IEA, Rhea reaction mapping). Reason: Consistent with the EC 2.7.11.1 catalytic activity. |
| GO:1901796 regulation of signal transduction by p53 class mediator | TAS Reactome:R-HSA-6804756 | KEEP AS NON CORE | Summary: Regulation of p53-class signaling (Reactome TAS) via CHK1 phosphorylation of TP53. Reason: CHK1 phosphorylates p53 (e.g. S20) to stabilize/activate it; a genuine but downstream, context-specific role. Non-core. Supporting Evidence: Reactome:R-HSA-6804756 CHEK1-mediated phosphorylation of TP53 at S20 |
| GO:1901988 negative regulation of cell cycle phase transition | IEA GO_REF:0000117 | ACCEPT | Summary: Negative regulation of cell cycle phase transition (IEA/ARBA). Reason: Correct high-level BP: CHK1 restrains CDK-driven phase transitions at checkpoints. |
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Download this section (compressed HTML)Q: Which human CHK1 substrates identified by analog-sensitive phosphoproteomics (e.g. KAP1/TRIM28 Ser473, FEN1, RIF1, Treslin/TICRR) are direct in vivo targets with defined checkpoint consequences, versus in vitro candidates?
Q: Is WEE1 a direct human CHK1 substrate, or is CHK1 regulation of WEE1 principally indirect through the FAM122A-PP2A-B55alpha axis?
Q: How is CHK1 signaling terminated during checkpoint recovery, and how do SCF(FBXO6) degradation, hHR23A-mediated basal turnover, and PPM1D/PP1/PP2A dephosphorylation quantitatively partition this control?
Experiment: Analog-sensitive CHK1 (gatekeeper mutant) with a bulky ATP analog plus rapid inhibition and quantitative phosphoproteomics in synchronized cells to distinguish direct, cell-cycle-resolved CHK1 substrates from indirect targets.
Experiment: Degron-based acute CHK1 depletion combined with DNA fiber assays and origin-mapping to separate CHK1 control of origin firing from its control of fork stability in unperturbed versus stressed S phase.
Experiment: Separation-of-function CHK1 phosphosite/localization mutants (Ser317, Ser345, Ser296, centrosome-tethered) to map how compartmentalization directs distinct substrate sets (nuclear CDC25A/C versus centrosomal CDK1 shielding).
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