Ser33
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Home > Phosphorylation Site Page: > Ser33  -  Chk2 (human)

Site Information
tQsQGSSsQsQGIss   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447549

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 1 ) , immunoprecipitation ( 4 ) , mass spectrometry ( 8 ) , mutation of modification site ( 9 , 11 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 )
Disease tissue studied:
ataxia-telangiectasia ( 3 , 10 ) , colorectal cancer ( 6 ) , colorectal carcinoma ( 6 ) , cancer, squamous cell carcinoma ( 1 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 2 ) , AT1ABR (lymphoblastoid) ( 10 ) , AT52RM (lymphoblastoid) ( 3 , 9 ) , BT (epithelial) ( 10 ) , C3ABR (lymphoblastoid) ( 10 ) , CHO (fibroblast) ( 6 ) , E.coli (bacterial) ( 5 , 8 ) , GM07078 (lymphoblastoid) ( 3 , 9 ) , HCT15 (intestinal) ( 6 , 9 ) , HEK293T (epithelial) ( 4 ) , HeLa (cervical) ( 11 ) , HN31 ( 1 ) , HN5 (squamous) ( 1 ) , LBC-N ( 9 ) , LCL (lymphoblastoid) ( 3 , 7 ) , NBS-ILB1 (fibroblast) ( 3 ) , NHDF (fibroblast) ( 11 ) , SF9 ( 5 ) , SKNSH (neural crest) ( 11 ) , U2OS (bone cell) [GR (human)] ( 11 )

Upstream Regulation
Regulatory protein:
Chk2 (human) ( 7 )
Putative in vivo kinases:
ATM (human) ( 11 )
Kinases, in vitro:
Chk2 (human) ( 5 )
Putative upstream phosphatases:
PPM1D (human) ( 3 ) , PPP1CA (human) ( 3 ) , PPP2CA (human) ( 3 )
Phosphatases, in vitro:
PPM1D (human) ( 6 )
Treatments:
4-nitroquinoline_1-oxide ( 9 ) , adriamycin ( 4 , 10 ) , hydroxyurea ( 4 , 9 ) , ionizing_radiation ( 2 , 4 , 7 , 9 , 11 ) , mitomycin_C ( 4 ) , NAC ( 10 ) , okadaic_acid ( 4 ) , UV ( 4 ) , VRX0466617 ( 7 ) , wortmannin ( 4 )

Downstream Regulation
Effects of modification on Chk2:
enzymatic activity, induced ( 9 ) , molecular association, regulation ( 4 , 9 )
Effects of modification on biological processes:
cell cycle regulation ( 9 )
Induce interaction with:
Chk2 (human) ( 9 )
Inhibit interaction with:
PPP2CA (human) ( 4 )

Disease / Diagnostics Relevance
Relevant diseases:
HNSCC ( 1 )

References 

1

Frederick MJ, et al. (2011) Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples. Am J Pathol 178, 548-71
21281788   Curated Info

2

Guo X, et al. (2010) Interdependent phosphorylation within the kinase domain T-loop Regulates CHK2 activity. J Biol Chem 285, 33348-57
20713355   Curated Info

3

Carlessi L, Buscemi G, Fontanella E, Delia D (2010) A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage. Biochim Biophys Acta 1803, 1213-23
20599567   Curated Info

4

Freeman AK, Dapic V, Monteiro AN (2010) Negative regulation of CHK2 activity by protein phosphatase 2A is modulated by DNA damage. Cell Cycle 9, 736-47
20160490   Curated Info

5

Gabant G, et al. (2008) Autophosphorylated residues involved in the regulation of human chk2 in vitro. J Mol Biol 380, 489-503
18538787   Curated Info

6

Oliva-Trastoy M, et al. (2007) The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene 26, 1449-58
16936775   Curated Info

7

Carlessi L, et al. (2007) Biochemical and cellular characterization of VRX0466617, a novel and selective inhibitor for the checkpoint kinase Chk2. Mol Cancer Ther 6, 935-44
17363488   Curated Info

8

King JB, et al. (2007) Identification of protein phosphorylation sites within Ser/Thr-rich cluster domains using site-directed mutagenesis and hybrid linear quadrupole ion trap Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 21, 3443-51
17918214   Curated Info

9

Buscemi G, et al. (2006) DNA damage-induced cell cycle regulation and function of novel Chk2 phosphoresidues. Mol Cell Biol 26, 7832-45
16940182   Curated Info

10

Kurz EU, Douglas P, Lees-Miller SP (2004) Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J Biol Chem 279, 53272-81
15489221   Curated Info

11

Mochan TA, Venere M, DiTullio RA, Halazonetis TD (2003) 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res 63, 8586-91
14695167   Curated Info

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