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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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Protein Name: Serine/threonine-protein kinase Chk2

UniprotKB/SwissProt ID: CHK2_HUMAN (O96017)

Gene Name: CHEK2

Synonyms: CDS1, CHK2, RAD53

Organism: Homo sapiens (Human).

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.

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Isoform 2: Nucleus. Note=Isoform 10 is present throughout the cell. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 9: Nucleus. Isoform 12: Nucleus. Nucleus, PML body. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53.

PDB :
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Protein disease:
Disease database Database Entry Disease information
HPRD05084Breast cancer, susceptibility to
HPRD05084Li-Fraumeni syndrome 2
HPRD05084Osteosarcoma, somatic
HPRD05084Prostate cancer, somatic
HPRD05084Prostate cancer, susceptibility to
Network with metabolic pathway:
Kegg map ID Pathway Link
map04115p53 signaling pathway
map04110Cell cycle
map05166HTLV-I infection
Graphical Visualization of S-nitrosylation Sites:
Overview of Protein S-nitrosylation Sites with Functional and Structural Information
InterPro ID Domain
IPR000253
IPR000719
IPR002290
IPR008271
IPR008984
IPR011009