Regulatory Network in Protein Phosphorylation
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Kinase: CHK1 CHK1 checkpoint homolog (S. pombe)

Group: CAMK      Family: CAMKL      Subfamily: CHK1

Description: CHK1 checkpoint homolog (S. pombe)

Gene Symbol: CHEK1

Synonyms: CHK1

UniprotKB/SwissProt: CHK1_HUMAN (O14757)

Function: Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. Recognizes the substrate consensus sequence [R-X-X- S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. 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. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser- 293' promotes proteolysis of CDC25A. Inhibition of CDC25 activity leads to increased inhibitory tyrosine phosphorylation of CDK- cyclin complexes and blocks cell cycle progression. Binds to and phosphorylates RAD51 at 'Thr-309', which may enhance the association of RAD51 with chromatin and promote DNA repair by homologous recombination. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may affect chromatin assembly during S phase or DNA repair. May also phosphorylate multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and enhances suppression of cellular proliferation.

Subcellular Localization: Nucleus. Cytoplasm. Note=Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B.

Protein Domain:
PDB:1IA8

The substrate proteins of kinase CHK1

No.Gene NameUniProtKB IDProtein DescriptionNumber of kinase-specific phosphorylation sitesView
1CLSPNCLSPN_HUMANClaspin (hClaspin) (Hu-Claspin). 1Show
2MCM4MCM4_HUMANDNA replication licensing factor MCM4 (CDC21 homolog) (P1-CDC21). 1Show
3CDC25AMPIP1_HUMANM-phase inducer phosphatase 1 (EC 3.1.3.48) (Dual specificityphosphatase Cdc25A). 17Show
4CDC25CMPIP3_HUMANM-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificityphosphatase Cdc25C). 2Show
5TP53P53_HUMANCellular tumor antigen p53 (Tumor suppressor p53) (Phosphoprotein p53)(Antigen NY-CO-13). 3Show
6TP73P73_HUMANTumor protein p73 (p53-like transcription factor) (p53-relatedprotein). 1Show
7RAD51RAD51_HUMANDNA repair protein RAD51 homolog 1 (hRAD51) (HsRAD51). 1Show
8TLK1TLK1_HUMANSerine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (Tousled-like kinase 1) (PKU-beta). 2Show



The substrate proteins of kinase family CHK1

No.Gene NameUniProtKB IDProtein DescriptionNumber of kinase family-specific phosphorylated sitesView
1CLSPNCLSPN_HUMANClaspin (hClaspin) (Hu-Claspin). 1Show
2MCM4MCM4_HUMANDNA replication licensing factor MCM4 (CDC21 homolog) (P1-CDC21). 1Show
3CDC25AMPIP1_HUMANM-phase inducer phosphatase 1 (EC 3.1.3.48) (Dual specificityphosphatase Cdc25A). 17Show
4CDC25CMPIP3_HUMANM-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificityphosphatase Cdc25C). 2Show
5TP53P53_HUMANCellular tumor antigen p53 (Tumor suppressor p53) (Phosphoprotein p53)(Antigen NY-CO-13). 3Show
6TP73P73_HUMANTumor protein p73 (p53-like transcription factor) (p53-relatedprotein). 1Show
7RAD51RAD51_HUMANDNA repair protein RAD51 homolog 1 (hRAD51) (HsRAD51). 1Show
8TLK1TLK1_HUMANSerine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (Tousled-like kinase 1) (PKU-beta). 2Show