Regulatory Network in Protein Phosphorylation
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Substrate: CHEK1

Description: Serine/threonine-protein kinase Chk1 (EC 2.7.11.1).

Synonyms: CHK1

Ensembl ID: ENSG00000149554

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.

Other Modifications: View all modification sites in dbPTM

Protein 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.
PDB:1IA8
Protein Domain and Phosphorylation Sites:

The phosphorylated sites of CHEK1

No.SubstrateUniProtKB IDPositionPhosphoPeptideSolvent AccessibilityCatalytic kinaseSourceComputational Annotation of Catalytic KinaseInteracting PartnersExpression Analysis
1CHEK1CHK1_HUMANS280RPRVT S GGVSE 30.60%AKT1 HPRD:04356(in vitro)  ViewAnalyzing
2CHEK1CHK1_HUMANS280RPRVT S GGVSE 30.60%AKT_group Phospho.ELM 7.0 ViewAnalyzing
3CHEK1CHK1_HUMANS280RPRVT S GGVSE 30.60%AKT1(PKB)  Swiss-Prot 55.0 (Similarity) ViewAnalyzing
4CHEK1CHK1_HUMANS296SKHIQ S NLDFS 38.46% Swiss-Prot 55.0 View   
5CHEK1CHK1_HUMANS296SKHIQ S NLDFS 38.46% Phospho.ELM 7.0View   
6CHEK1CHK1_HUMANS308VNSAS S EENVK 48.96% Swiss-Prot 55.0 View   
7CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATM Swiss-Prot 55.0   ViewAnalyzing
8CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATM HPRD:04356(in vitro;in vivo)  ViewAnalyzing
9CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATR Swiss-Prot 55.0   ViewAnalyzing
10CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATR Phospho.ELM 7.0  ViewAnalyzing
11CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATR HPRD:04356(in vitro;in vivo)  ViewAnalyzing
12CHEK1CHK1_HUMANS317VKYSS S QPEPR 43.76%ATM Phospho.ELM 7.0  ViewAnalyzing
13CHEK1CHK1_HUMANS345QGISF S QPTCP 28.58%ATM Phospho.ELM 7.0  ViewAnalyzing
14CHEK1CHK1_HUMANS345QGISF S QPTCP 28.58%ATR HPRD:04356(in vitro;in vivo)  ViewAnalyzing
15CHEK1CHK1_HUMANS345QGISF S QPTCP 28.58%ATR Swiss-Prot 55.0   ViewAnalyzing
16CHEK1CHK1_HUMANS345QGISF S QPTCP 28.58%ATM Swiss-Prot 55.0   ViewAnalyzing
17CHEK1CHK1_HUMANS345QGISF S QPTCP 28.58%ATR Phospho.ELM 7.0  ViewAnalyzing