chk1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Chk1 is a nuclear kinase; this is its site of action where it is activated by Rad3 and phosphorylates nuclear substrates (Cdc25, Wee1, Cdc10). Phylogenetic inference is consistent with direct experimental nuclear localization. Reason: Nuclear localization is supported experimentally (IDA, HDA) and by UniProt subcellular location, consistent with Chk1's function in the nucleus. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IBA GO_REF:0000033	ACCEPT	Summary: This is the core biological process of Chk1 as the effector kinase of the G2/M DNA damage checkpoint. Strongly supported by phylogenetic inference and abundant experimental evidence. Reason: Core function; corroborated by multiple experimental annotations (IDA/IMP/EXP). Supporting Evidence: PMID:8497322 we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present. We have called the gene encoding this protein chk1 for checkpoint kinase.
GO:0035861 site of double-strand break	IBA GO_REF:0000033	ACCEPT	Summary: Chk1 is recruited to and active at sites of DNA double-strand breaks, where it is activated by Rad3 via the Crb2 mediator; Chk1-GFP forms foci colocalizing with Crb2/Rad22 at DSBs. Phylogenetic inference matches the experimental IDA. Reason: Recruitment to DSBs is directly demonstrated experimentally and consistent with phylogenetic inference. Supporting Evidence: PMID:22792081 Crb2 recruits Chk1 to double-strand breaks (DSBs) through a direct physical interaction.
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: A cytoplasmic pool is reported by high-throughput and IDA localization, but Chk1's documented function (activation by Rad3, phosphorylation of Cdc25/Wee1/Cdc10, DSB foci) is nuclear. The cytoplasmic localization is not a site of established function. Reason: Cytoplasmic localization is observed but does not correspond to Chk1's site of action, which is nuclear; retain as non-core context. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0000077 DNA damage checkpoint signaling	IEA GO_REF:0000002	ACCEPT	Summary: General DNA damage checkpoint signaling is correct for Chk1 and is the parent of the more specific mitotic G2 DNA damage checkpoint signaling term that is also annotated. Accepted as a correct, if less specific, process term. Reason: Correct process; the more specific GO:0007095 is preferred for representing the core function but this parent term is not wrong. Supporting Evidence: PMID:8497322 we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: Chk1 is a protein kinase; this InterPro-based term is correct but is a general parent of the experimentally supported protein serine/threonine kinase activity. Reason: The essence is correct but a more specific child term (protein serine/threonine kinase activity) is experimentally supported and preferred. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function. Chk1 is a Ser/Thr protein kinase (EC 2.7.11.1) that phosphorylates Cdc25, Wee1, and Cdc10. Supported by IEA and multiple direct experimental assays. Reason: Core catalytic function, supported by direct in vitro kinase assays. Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: As an active protein kinase with a conserved ATP-binding P-loop (residues 16-24, 38), ATP binding is a correct and expected molecular function. Reason: Supported by the conserved protein kinase domain and ATP-binding motif in the sequence. Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Nuclear localization from UniProt subcellular location mapping; consistent with experimental localization and Chk1's nuclear function. Reason: Redundant with the experimental nucleus annotation but correct. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea/EC-based term capturing serine phosphorylation activity; correct and consistent with the broader protein serine/threonine kinase activity. Reason: Correct molecular function consistent with EC 2.7.11.1. Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0005515 protein binding	IPI PMID:14739927 Regulation of checkpoint kinases through dynamic interaction...	MARK AS OVER ANNOTATED	Summary: This IPI captures the Chk1-Crb2 interaction. The bare protein binding term is uninformative; the meaningful function is Chk1's regulated interaction with the BRCT-mediator Crb2 that is required for Chk1 activation. Reason: Bare protein binding is uninformative per curation guidelines; the underlying Crb2 interaction is better captured by the checkpoint signaling process terms. Supporting Evidence: PMID:14739927 Crb2 regulates DNA damage checkpoint through temporal and dynamic interactions with Rad3, Chk1 and replication factor Cut5.
GO:0005515 protein binding	IPI PMID:15229228 Homo-oligomerization is the essential function of the tandem...	UNDECIDED	Summary: A protein binding IPI annotation referencing PMID:15229228, which is not available in the cached publications, so the specific interaction partner and its significance cannot be verified. Reason: The supporting publication (PMID:15229228) could not be accessed; bare protein binding is in any case uninformative.
GO:0005515 protein binding	IPI PMID:17502373 Fission yeast Rnf4 homologs are required for DNA repair.	MARK AS OVER ANNOTATED	Summary: Captures the Chk1-Rfp1 two-hybrid interaction. Bare protein binding is uninformative, and rfp1/rfp2 mutants retain normal checkpoint signaling to Chk1, so this interaction is not part of Chk1's core checkpoint function. Reason: Uninformative bare protein binding; the interaction is peripheral (DNA repair/SUMO context) rather than core to Chk1 function. Supporting Evidence: PMID:17502373 Rfp1 was isolated as a Chk1-interacting protein in a two-hybrid screen and has high amino acid sequence similarity to Rfp2.
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-SPO-75040	ACCEPT	Summary: Reactome annotation (Phosphorylation of Wee1 kinase by Chk1) supporting Chk1's Ser/Thr kinase activity. Correct core molecular function. Reason: Consistent with experimentally demonstrated kinase activity toward Wee1. Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0005515 protein binding	IPI PMID:22792081 Phosphorylation-dependent interactions between Crb2 and Chk1...	MARK AS OVER ANNOTATED	Summary: Captures the phosphorylation-dependent Chk1-Crb2 interaction at DSBs. Bare protein binding is uninformative; the functional significance is recruitment of Chk1 to DSBs for activation. Reason: Bare protein binding term is uninformative; the biology is better captured by the DSB localization and checkpoint signaling annotations. Supporting Evidence: PMID:22792081 Crb2 recruits Chk1 to double-strand breaks (DSBs) through a direct physical interaction.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IMP PMID:22792081 Phosphorylation-dependent interactions between Crb2 and Chk1...	ACCEPT	Summary: Direct genetic/cell-biological evidence that Chk1 acts in the G2 DNA damage checkpoint, with its recruitment and activation at DSBs required for checkpoint arrest. Core function. Reason: Core function supported by mutant phenotype analysis (crb2 SQ/TQ mutants abolish Chk1 activation and checkpoint arrest). Supporting Evidence: PMID:22792081 A pair of conserved SQ/TQ motifs in Crb2, which are consensus phosphorylation sites of upstream kinase Rad3, is required for Chk1 recruitment and activation.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:9034337 Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibi...	ACCEPT	Summary: Direct in vitro demonstration of Chk1 Ser/Thr kinase activity, phosphorylating Wee1. Core molecular function. Reason: Direct experimental assay of kinase activity. Supporting Evidence: PMID:9034337 p56chk1 can phosphorylate p107wee1 directly in vitro.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IDA PMID:9034337 Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibi...	ACCEPT	Summary: Chk1 overexpression and UV-induced delay depend on Wee1, with Chk1 phosphorylating Wee1 to maintain Cdc2-Y15 phosphorylation and G2 delay. Core function. Reason: Core checkpoint function demonstrated through the Chk1-Wee1-Cdc2 axis. Supporting Evidence: PMID:9034337 wee1 is required for cell cycle arrest induced by up-regulation of an essential component of this checkpoint, chk1.
GO:0051598 meiotic recombination checkpoint signaling	IMP PMID:29123917 The telomere bouquet facilitates meiotic prophase progressio...	KEEP AS NON CORE	Summary: Chk1 (with Rad3) responds to persistent meiotic recombination DNA damage to restrain meiotic prophase exit (the post-horsetail bouquet stage). A specialized, non-core role distinct from the mitotic checkpoint. Reason: Genuine but specialized meiotic function; not the defining mitotic checkpoint role of Chk1. Supporting Evidence: PMID:29123917 Persistent DNA damages, induced during meiotic recombination, activate the Rad3 and Chk1 DNA damage checkpoint kinases and extend the bouquet stage beyond the chromosome oscillation period.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:9774107 Replication checkpoint requires phosphorylation of the phosp...	ACCEPT	Summary: Chk1 phosphorylates Cdc25 (at S99, S192, S359), demonstrating Ser/Thr kinase activity on a physiological substrate. Core molecular function. Reason: Direct evidence of kinase activity toward Cdc25. Supporting Evidence: PMID:9774107 both kinases phosphorylate Cdc25 on the same sites, which include serine residues at positions 99, 192 and 359.
GO:0005515 protein binding	IPI PMID:9278510 Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint...	MARK AS OVER ANNOTATED	Summary: Captures the Chk1-Cdc25 interaction (Cdc25 copurifies with and is phosphorylated by Chk1). Bare protein binding is uninformative; the meaningful relationship is Chk1's kinase-substrate action on Cdc25. Reason: Bare protein binding is uninformative; the Cdc25 interaction is better represented by Chk1's kinase activity and checkpoint signaling annotations. Supporting Evidence: PMID:9278510 Cdc25 associated with Chk1 in vivo and was phosphorylated when copurified in Chk1 complexes.
GO:0006281 DNA repair	EXP NOT PMID:8497322 Fission yeast chk1 protein kinase links the rad checkpoint p...	ACCEPT	Summary: Correctly negated. Chk1 is a checkpoint signaling kinase that arrests the cell cycle in response to damage but does not itself carry out DNA repair. Reason: The NOT annotation appropriately distinguishes checkpoint signaling from the repair machinery; Chk1 signals arrest, it does not repair DNA. Supporting Evidence: PMID:8497322 we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	EXP PMID:8497322 Fission yeast chk1 protein kinase links the rad checkpoint p...	ACCEPT	Summary: Original identification of chk1 as the checkpoint kinase required for cell-cycle arrest after DNA damage. Core function. Reason: Foundational experimental evidence for Chk1's core checkpoint role. Supporting Evidence: PMID:8497322 We have called the gene encoding this protein chk1 for checkpoint kinase.
GO:0005515 protein binding	IPI PMID:26131711 Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and ...	MARK AS OVER ANNOTATED	Summary: A protein binding IPI annotation arising from a study of Cdc2 phospho-forms and the DNA damage response. Bare protein binding is uninformative and the specific interaction is not a defining Chk1 function. Reason: Uninformative bare protein binding term; not central to Chk1's characterized function. Supporting Evidence: PMID:26131711 The activity of Cdc2 (CDK1) kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15) by Wee1 kinase in the presence of DNA damage.
GO:0005634 nucleus	IDA PMID:11553781 Serine-345 is required for Rad3-dependent phosphorylation an...	ACCEPT	Summary: Direct experimental nuclear localization; Chk1 is active in the nucleus where it is phosphorylated by Rad3 and inhibits Cdc25. Core localization. Reason: Direct evidence consistent with Chk1's nuclear site of action. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0005737 cytoplasm	IDA PMID:11553781 Serine-345 is required for Rad3-dependent phosphorylation an...	KEEP AS NON CORE	Summary: A cytoplasmic pool is reported, but Chk1's documented functions are nuclear. Retain as non-core localization context rather than a site of established function. Reason: Cytoplasmic localization observed but not the site of Chk1's characterized activity. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IMP PMID:11553781 Serine-345 is required for Rad3-dependent phosphorylation an...	ACCEPT	Summary: chk1-S345A cells are checkpoint defective and DNA-damage sensitive, demonstrating Chk1's requirement for the G2-M DNA damage checkpoint. Core function. Reason: Mutant phenotype directly demonstrates the core checkpoint role. Supporting Evidence: PMID:11553781 The chk1-S345A cells are sensitive to DNA damage and are checkpoint defective.
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IGI PMID:25533348 Tolerance of deregulated G1/S transcription depends on criti...	ACCEPT	Summary: Chk1 negatively regulates the G2/M transition, the molecular consequence of its inhibition of Cdc25 and activation of Wee1. Consistent with its checkpoint role. Reason: Correct downstream consequence of Chk1 checkpoint signaling; supported by genetic interaction. Supporting Evidence: PMID:9278510 Expression of large amounts of Chk1 produced the same phenotype as did loss of the cdc25 gene in cdc2-3w cells.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IMP PMID:9042863 Cdc2 tyrosine phosphorylation is required for the DNA damage...	ACCEPT	Summary: Establishes that the Chk1-mediated G2 DNA damage checkpoint operates through inhibitory Cdc2-Y15 phosphorylation (Wee1/Mik1). Core function. Reason: Supports the mechanistic basis of Chk1's core G2 checkpoint function. Supporting Evidence: PMID:9042863 the G2 DNA damage checkpoint arrest in S. pombe depends on the inhibitory tyrosine phosphorylation of Cdc2 carried out by the Wee1 and Mik1 kinases.
GO:0000785 chromatin	IDA PMID:24006488 The DNA damage and the DNA replication checkpoints converge ...	KEEP AS NON CORE	Summary: Chk1 associates with chromatin in the context of regulating the MBF transcription factor (phosphorylating Cdc10 and releasing MBF from chromatin). A genuine but secondary localization tied to its transcriptional-repression role. Reason: Chromatin association is real but reflects the secondary MBF/transcription role rather than the core checkpoint signaling function. Supporting Evidence: PMID:24006488 This modification is responsible for the repression of MBF-dependent transcription through induced release of MBF from chromatin.
GO:0035861 site of double-strand break	IDA PMID:22792081 Phosphorylation-dependent interactions between Crb2 and Chk1...	ACCEPT	Summary: Chk1-GFP forms foci at IR- and HO-induced DSBs that colocalize with Crb2/Rad22; recruitment to DSBs is where Chk1 is activated. Core localization for its checkpoint function. Reason: Directly demonstrated DSB localization integral to Chk1 activation. Supporting Evidence: PMID:22792081 Crb2 recruits Chk1 to double-strand breaks (DSBs) through a direct physical interaction.
GO:0044773 mitotic DNA damage checkpoint signaling	IGI PMID:12186947 A novel chk1-dependent G1/M checkpoint in fission yeast.	ACCEPT	Summary: Chk1 is required for a checkpoint arrest in G1/early cell cycle in pre-RC mutant cells, broadening its checkpoint role beyond late S/G2. Consistent with Chk1's checkpoint signaling function. Reason: Genetic evidence for Chk1 in mitotic DNA damage checkpoint signaling (G1/M arrest). Supporting Evidence: PMID:12186947 The arrest depends upon the checkpoint Rad proteins and, surprisingly, the Chk1 protein, which is thought to act only from late S phase.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:24006488 The DNA damage and the DNA replication checkpoints converge ...	KEEP AS NON CORE	Summary: Upon DNA damage Chk1 phosphorylates the MBF subunit Cdc10, repressing MBF-dependent S-phase gene transcription. A genuine downstream effector branch of the DNA damage response, secondary to the core checkpoint-arrest function. Reason: Real but secondary transcriptional-repression role mediated via Cdc10/MBF. Supporting Evidence: PMID:24006488 Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible for the repression of MBF-dependent transcription through induced release of MBF from chromatin.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:24006488 The DNA damage and the DNA replication checkpoints converge ...	ACCEPT	Summary: Chk1 phosphorylates Cdc10 (MBF) on Ser-720/Ser-732, a direct demonstration of its Ser/Thr kinase activity on a physiological substrate. Core molecular function. Reason: Direct evidence of kinase activity toward Cdc10. Supporting Evidence: PMID:24006488 This is achieved by direct phosphorylation of Cdc10 at Ser-720 and Ser-732 by the effector kinase Chk1.
GO:0044773 mitotic DNA damage checkpoint signaling	IMP PMID:24006488 The DNA damage and the DNA replication checkpoints converge ...	ACCEPT	Summary: Chk1 activation by DNA-damaging agents and Cdc10 phosphorylation is part of the DNA damage checkpoint response. Consistent with Chk1's checkpoint signaling function. Reason: Supports Chk1's role in mitotic DNA damage checkpoint signaling. Supporting Evidence: PMID:24006488 When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain.
GO:0005634 nucleus	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	ACCEPT	Summary: High-throughput localization confirming nuclear presence, consistent with IDA data and Chk1's nuclear function. Reason: Corroborates the nuclear localization of Chk1. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0005737 cytoplasm	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	KEEP AS NON CORE	Summary: High-throughput cytoplasmic localization. Chk1's documented functions are nuclear; retain as non-core context. Reason: Observed cytoplasmic signal does not correspond to a site of established function. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0005829 cytosol	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	KEEP AS NON CORE	Summary: High-throughput cytosolic localization. As with the cytoplasm annotations, this is not the site of Chk1's characterized nuclear function. Reason: Observed cytosolic signal does not correspond to Chk1's site of action. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0005654 nucleoplasm	TAS Reactome:R-SPO-75040	ACCEPT	Summary: Nucleoplasmic localization (Reactome) consistent with Chk1's nuclear function in phosphorylating Wee1/Cdc25. Correct. Reason: Consistent with nuclear localization and function. Supporting Evidence: PMID:11553781 This checkpoint is enforced by Chk1, a protein kinase that inhibits the mitotic inducer Cdc25.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:10825192 Mechanism of caffeine-induced checkpoint override in fission...	ACCEPT	Summary: Study of caffeine-mediated checkpoint override assays Chk1 phosphorylation/activity; supports Chk1 Ser/Thr kinase activity downstream of Rad3. Core molecular function. Reason: Consistent with Chk1's experimentally demonstrated kinase activity. Supporting Evidence: PMID:10825192 Caffeine prevented activation of Cds1 and phosphorylation of Chk1, two protein kinases that enforce the S-M checkpoint triggered by hydroxyurea.

Gene Description

Existing Annotations Review

Core Functions

Effector serine/threonine protein kinase of the mitotic G2/M DNA-damage checkpoint; phosphorylates and inhibits the Cdc25 phosphatase and phosphorylates the Wee1 kinase to maintain inhibitory Cdc2/CDK1 tyrosine-15 phosphorylation and block mitotic entry.

DNA-damage-induced transcriptional repressor of S-phase (MBF) genes; phosphorylates the MBF core subunit Cdc10 to release MBF from chromatin and downregulate G1/S transcription.

References

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