Thr387
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Home > Phosphorylation Site Page: > Thr387  -  Chk2 (human)

Site Information
LMRtLCGtPtyLAPE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447552

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 7 , 18 , 19 ) , electrophoretic mobility shift ( 7 , 15 ) , immunoprecipitation ( 2 , 9 ) , mass spectrometry ( 1 , 3 , 4 , 8 , 9 ) , mutation of modification site ( 4 , 7 , 9 , 12 , 18 , 19 ) , phospho-antibody ( 2 , 4 , 5 , 7 , 8 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 ) , phosphopeptide mapping ( 7 , 8 , 18 ) , western blotting ( 2 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 15 , 17 )
Disease tissue studied:
ataxia-telangiectasia ( 5 , 15 ) , bone cancer ( 2 , 7 ) , brain cancer ( 15 ) , glioblastoma ( 15 ) , glioma ( 15 ) , breast cancer ( 3 ) , HER2 positive breast cancer ( 1 ) , luminal A breast cancer ( 1 ) , luminal B breast cancer ( 1 ) , breast cancer, surrounding tissue ( 1 ) , breast cancer, triple negative ( 1 , 3 ) , colorectal cancer ( 10 ) , colorectal carcinoma ( 10 ) , ovarian cancer ( 3 ) , Nijmegen Breakage Syndrome ( 15 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 4 , 7 , 9 , 15 , 18 ) , A253 ( 17 ) , AT52RM (lymphoblastoid) ( 5 , 12 ) , breast ( 1 , 3 ) , CHO (fibroblast) ( 10 , 15 ) , E.coli (bacterial) ( 8 ) , fibroblast ( 15 ) , GM07078 (lymphoblastoid) ( 5 , 12 ) , HCT15 (intestinal) ( 10 ) , HEK293T (epithelial) ( 19 ) , HeLa (cervical) ( 18 ) , LBC-N ( 12 ) , LCL (lymphoblastoid) ( 5 , 11 , 16 ) , M059J (glial) ( 15 ) , M059K (glial) ( 15 ) , MEF (fibroblast) ( 7 ) , MEF (fibroblast) [IGF1R (mouse)] ( 18 ) , NBS-ILB1 (fibroblast) ( 5 ) , ovary ( 3 ) , OVCAR3 (ovarian) ( 14 ) , SF9 ( 8 ) , U2OS (bone cell) [GR (human)] ( 19 ) , U2OS (bone cell) ( 2 , 7 )

Upstream Regulation
Regulatory protein:
Tax (retrovirus) ( 9 )
Putative in vivo kinases:
Chk2 (human) ( 7 , 18 , 19 )
Kinases, in vitro:
Chk2 (human) ( 7 , 18 ) , DNAPK (human) ( 15 )
Putative upstream phosphatases:
PPM1D (human) ( 5 ) , PPP1CA (human) ( 5 ) , PPP2CA (human) ( 5 )
Treatments:
caffeine ( 14 ) , camptothecin ( 15 ) , etoposide ( 2 ) , ionizing_radiation ( 4 , 9 , 11 , 12 , 15 , 16 , 18 , 19 ) , methylselenocysteine ( 17 ) , resveratrol ( 14 ) , SN-38 ( 17 ) , VRX0466617 ( 11 )

Downstream Regulation
Effects of modification on Chk2:
enzymatic activity, induced ( 4 , 13 , 16 , 18 , 19 ) , intracellular localization ( 4 , 9 ) , protein conformation ( 13 )
Effects of modification on biological processes:
cell cycle regulation ( 16 )

References 

1

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

2

Magni M, et al. (2015) CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage. Oncotarget 6, 17817-31
26158765   Curated Info

3

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

4

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

5

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

6

Li J, et al. (2008) Chk2 oligomerization studied by phosphopeptide ligation: implications for regulation and phosphodependent interactions. J Biol Chem 283, 36019-30
18948271   Curated Info

7

Lovly CM, et al. (2008) Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379. Mol Cell Biol 28, 5874-85
18644861   Curated Info

8

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

9

Gupta SK, et al. (2007) Human T-cell leukemia virus type 1 Tax oncoprotein prevents DNA damage-induced chromatin egress of hyperphosphorylated Chk2. J Biol Chem 282, 29431-40
17698850   Curated Info

10

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

11

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

12

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

13

Oliver AW, et al. (2006) Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange. EMBO J 25, 3179-90
16794575   Curated Info

14

Tyagi A, et al. (2005) Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3 cells. Carcinogenesis 26, 1978-87
15975956   Curated Info

15

Li J, Stern DF (2005) Regulation of CHK2 by DNA-dependent protein kinase. J Biol Chem 280, 12041-50
15668230   Curated Info

16

Buscemi G, et al. (2004) Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks. Oncogene 23, 7691-700
15361830   Curated Info

17

Yin MB, et al. (2004) Enhanced 7-ethyl-10-hydroxycamptothecin (SN-38) lethality by methylselenocysteine is associated with Chk2 phosphorylation at threonine-68 and down-regulation of Cdc6 expression. Mol Pharmacol 66, 153-60
15213307   Curated Info

18

Schwarz JK, Lovly CM, Piwnica-Worms H (2003) Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Mol Cancer Res 1, 598-609
12805407   Curated Info

19

Lee CH, Chung JH (2001) The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation. J Biol Chem 276, 30537-41
11390408   Curated Info