Summary

Name CHEK2
Full Name Serine/threonine-protein kinase Chk2
Synonyms CHK2 checkpoint homolog, Cds1 homolog, Hucds1, hCds1, Checkpoint kinase 2 | CDS1, CHK2, RAD53
Primary ID O96017
Links - -
Type protein
Relations 88
Pathways DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
Inhibitors SCHEMBL14517914; 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
Function Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation VHL 0.467
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PML 0.407
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation CDC25A 0.837
Publications: 4 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CDC25A 0.837
Publications: 7 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation AATF 0.365
Publications: 3 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TP53 0.784
Publications: 18 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation CHEK2 0.83
Publications: 8 Organism: Homo Sapiens, In Vitro
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation TP53 0.784
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates activity img/direct_inhibition.png phosphorylation CDC25C 0.852
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PSME3 0.355
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RASGRF1 0.378
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MDM4 0.713
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation E2F1 0.5
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png phosphorylation E2F1 0.5
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MDM4 0.713
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FOXM1 0.71
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CHEK2 0.2
Publications: 5 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SOD1 0.384
Publications: 2 Organism: Saccharomyces Cerevisiae
+ up-regulates activity img/direct-activation.png phosphorylation RB1 0.433
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation CHEK2 0.644
Publications: 2 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation BECN1 0.303
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation BRCA1 0.78
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, Cell cycle: G2/M phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation BLM 0.543
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation CHEK2 0.504
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation XRCC1 0.531
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation TTK 0.296
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TTK 0.296
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK2 0.504
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK2 0.609
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png dephosphorylation CHEK2 0.314
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation CHEK2 0.442
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK2 0.296
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation CHEK2 0.59
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation CHEK2 0.855
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates img/direct-activation.png phosphorylation KIT 0.291
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK2 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK2 0.8
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CHEK2 0.489
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CHEK2 0.527
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CHEK2 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PPP2R5C 0.327
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CHEK2 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates activity img/direct_inhibition.png acetylation CHEK2 0.2
Publications: 1 Organism: Homo Sapiens