Summary

Name CHEK1
Full Name Serine/threonine-protein kinase Chk1
Synonyms CHK1 checkpoint homolog, Cell cycle checkpoint kinase, Checkpoint kinase-1 | CHK1
Primary ID O14757
Links - -
Type protein
Relations 78
Pathways DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
Inhibitors 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide; 6-bromo-3-(1-methyl-4-pyrazolyl)-5-(3-piperidinyl)-7-pyrazolo[1,5-a]pyrimidinamine; LY2603618; SCHEMBL14517914; 7-Hydroxystaurosporine; 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea; CHIR-124
Function Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889, PubMed:14559997). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:9278511, PubMed:19734889, PubMed:20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation E2F6 0.556
Publications: 2 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation CDC25A 0.853
Publications: 6 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation E2F3 0.338
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TP53 0.773
Publications: 7 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ img/unknown.png phosphorylation RASSF1 0.364
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CDC25C 0.846
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation CDC25B 0.782
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NEK11 0.269
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CHEK1 0.443
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates img/direct_inhibition.png phosphorylation CHEK1 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation CHEK1 0.421
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK1 0.531
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SYK 0.317
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CHEK1 0.2
Publications: 2 Organism: Homo Sapiens, Xenopus Laevis
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ down-regulates activity img/direct_inhibition.png dephosphorylation CHEK1 0.47
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK1 0.841
Publications: 2 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation CHEK1 0.923
Publications: 2 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ down-regulates activity img/direct_inhibition.png dephosphorylation CHEK1 0.269
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFKB1 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation FANCD2 0.61
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AURKB 0.369
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM4 0.541
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation CHEK1 0.494
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation CHEK1 0.494
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MDM4 0.541
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PABIR1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FANCE 0.705
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TP73 0.515
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation SETMAR 0.508
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RB1 0.435
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation BLM 0.771
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TLK1 0.445
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation TLK2 0.275
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation H3-3A 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RAD51 0.837
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation CLSPN 0.787
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation SNCB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination CHEK1 0.463
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/indirect-activation.png CHEK1 0.508
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation WEE1 0.592
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation Histone H3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CHEK1 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CHEK1 0.787
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png MEK1/2 0.33
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png binding CHEK1 0.515
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates img/indirect-activation.png CHEK1 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding CHEK1 0.788
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates activity img/indirect_inhibition.png CHEK1 0.303
Publications: 1 Organism: Mus Musculus
Pathways:FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ up-regulates img/indirect-activation.png CHEK1 0.353
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK1 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CDC7 0.724
Publications: 1 Organism: Homo Sapiens