Ser345

Site Information
LVQGISFsQPTCPEH SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447834

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 22 ) , immunoassay ( 2 , 5 ) , mutation of modification site ( 17 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ) , western blotting ( 1 , 2 , 3 , 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 22 )
Disease tissue studied:	chronic myelogenous leukemia ( 1 )
Relevant cell line - cell type - tissue:	AC16 ( 2 ) , C2C12 (myoblast) ( 18 ) , CD8+ (T lymphocyte) ( 3 ) , EM-3 (bone cell) ( 1 ) , ES (stem) ( 17 ) , G361 (melanocyte) ( 23 ) , heart ( 2 ) , HEK293T (epithelial) ( 8 ) , HeLa (cervical) ( 10 ) , intestine ( 5 ) , KG-1a (myeloid) ( 4 ) , MEF (fibroblast) [homozygous knockout] ( 13 ) , MEF (fibroblast) [IGF1R (mouse)] ( 21 ) , MEF (fibroblast) [PTPN2 (mouse), homozygous knockout] ( 15 ) , MEF (fibroblast) ( 9 , 10 , 11 , 12 , 19 , 22 ) , MMTV-PyMT (breast cell) ( 14 ) , myocyte-heart ( 2 ) , parotid acinar-salivary gland ( 20 ) , parotid acinar-salivary gland [Akt1 (mouse)] ( 20 ) , skin ( 16 ) , SL13 (fibroblast) ( 8 )

Upstream Regulation
Regulatory protein:	Abl (mouse) ( 11 ) , Akt1 (mouse) ( 20 ) , ARID1A (human) ( 1 ) , ATM (mouse) ( 8 , 13 ) , ATR (mouse) ( 22 ) , CDT1 (human) ( 14 ) , EXO1 (mouse) ( 9 ) , JNK2 (mouse) ( 14 ) , MAPKAPK2 (mouse) ( 19 ) , MDM2 (mouse) ( 20 ) , POT1 (mouse) ( 12 , 13 ) , PPP5C (mouse) ( 10 ) , PTPN2 (human) ( 15 ) , SIRT1 (human) ( 2 )
Putative in vivo kinases:	ATR (human) ( 2 )
Treatments:	adenosine ( 3 ) , adriamycin ( 11 , 19 ) , aphidicolin ( 15 , 22 ) , AZD6738 ( 3 ) , caffeine ( 10 , 16 ) , cisplatin ( 4 , 19 ) , CPT ( 8 ) , cytidine ( 3 ) , D-phenylalanine ( 2 ) , delayed chromosome replication timing ( 18 ) , etoposide ( 20 ) , guanosine ( 3 ) , H2O2 ( 2 ) , hydroxyurea ( 14 , 23 ) , ionizing_radiation ( 22 , 23 ) , MMS ( 23 ) , olaparib ( 1 ) , serum ( 14 ) , siRNA ( 2 , 19 , 20 ) , teriflunomide ( 7 ) , thymidine ( 3 , 15 ) , TMZ ( 1 ) , tyrosine ( 2 ) , UV ( 9 , 10 , 16 , 17 , 23 )

Downstream Regulation
Effects of modification on Chk1:	intracellular localization ( 17 )
Effects of modification on biological processes:	apoptosis, altered ( 17 ) , cell cycle regulation ( 17 )

References
1	Yu ZC, et al. (2023) Temozolomide sensitizes ARID1A-mutated cancers to PARP inhibitors. Cancer Res 37306706 Curated Info
2	Zhao R, et al. (2023) Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response. Cell Rep 42, 112400 37071536 Curated Info
3	Sugitani N, et al. (2022) Thymidine rescues ATR kinase inhibitor-induced deoxyuridine contamination in genomic DNA, cell death, and interferon-α/β expression. Cell Rep 40, 111371 36130512 Curated Info
4	Kumar S, Tchounwou PB (2022) p53 as a unique target of action of cisplatin in acute leukaemia cells. J Cell Mol Med 26, 4727-4739 35946055 Curated Info
5	Yoshida A, et al. (2022) Non-phosphorylatable cyclin D1 mutant potentiates endometrial hyperplasia and drives carcinoma with Pten loss. Oncogene 41 35210557 Curated Info
6	Robles AJ, et al. (2020) Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts. Clin Cancer Res 32184294 Curated Info
7	Arnould S, et al. (2017) Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition. Oncotarget 8, 95206-95222 29221122 Curated Info
8	Lee SS, et al. (2015) ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells. Cell Rep 13, 1623-32 26586427 Curated Info
9	Lindsey-Boltz LA, et al. (2014) Coupling of human DNA excision repair and the DNA damage checkpoint in a defined in vitro system. J Biol Chem 289, 5074-82 24403078 Curated Info
10	Amable L, et al. (2011) Disruption of serine/threonine protein phosphatase 5 (PP5:PPP5c) in mice reveals a novel role for PP5 in the regulation of ultraviolet light-induced phosphorylation of serine/threonine protein kinase Chk1 (CHEK1). J Biol Chem 286, 40413-22 21921034 Curated Info
11	Wang X, et al. (2011) A positive role for c-Abl in Atm and Atr activation in DNA damage response. Cell Death Differ 18, 5-15 20798688 Curated Info
12	Gong Y, de Lange T (2010) A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion. Mol Cell 40, 377-87 21070964 Curated Info
13	Davoli T, Denchi EL, de Lange T (2010) Persistent telomere damage induces bypass of mitosis and tetraploidy. Cell 141, 81-93 20371347 Curated Info
14	Chen P, et al. (2010) Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model. PLoS One 5, e10443 20454618 Curated Info
15	Shields BJ, et al. (2008) DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression. Cancer Cell 14, 166-79 18691551 Curated Info
16	Lu YP, et al. (2008) Effect of caffeine on the ATR/Chk1 pathway in the epidermis of UVB-irradiated mice. Cancer Res 68, 2523-9 18381462 Curated Info
17	Niida H, et al. (2007) Specific role of Chk1 phosphorylations in cell survival and checkpoint activation. Mol Cell Biol 27, 2572-81 17242188 Curated Info
18	Chang BH, Smith L, Huang J, Thayer M (2007) Chromosomes with delayed replication timing lead to checkpoint activation, delayed recruitment of Aurora B and chromosome instability. Oncogene 26, 1852-61 17001311 Curated Info
19	Reinhardt HC, Aslanian AS, Lees JA, Yaffe MB (2007) p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 11, 175-89 17292828 Curated Info
20	Limesand KH, Schwertfeger KL, Anderson SM (2006) MDM2 is required for suppression of apoptosis by activated Akt1 in salivary acinar cells. Mol Cell Biol 26, 8840-56 16982679 Curated Info
21	Zinkel SS, et al. (2005) A role for proapoptotic BID in the DNA-damage response. Cell 122, 579-91 16122425 Curated Info
22	Brown EJ, Baltimore D (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17, 615-28 12629044 Curated Info
23	Sapkota GP, et al. (2002) Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366. Biochem J 368, 507-16 12234250 Curated Info