Ser428

Site Information
SSNSDGIsPKRRRLs SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 456320

In vivo Characterization
Methods used to characterize site in vivo:	flow cytometry ( 13 , 16 ) , immunoassay ( 2 , 9 ) , immunoprecipitation ( 3 , 13 , 15 , 16 , 20 ) , mass spectrometry ( 3 , 12 , 20 , 21 , 23 , 24 ) , modification-specific antibody ( 3 ) , mutation of modification site ( 3 , 13 , 15 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 22 , 25 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 22 )
Disease tissue studied:	bone cancer ( 3 , 9 ) , brain cancer ( 13 ) , glioblastoma ( 13 ) , glioblastoma multiforme ( 13 ) , glioma ( 13 ) , breast cancer ( 3 , 10 , 22 , 25 ) , HER2 positive breast cancer ( 12 ) , luminal A breast cancer ( 12 ) , luminal B breast cancer ( 12 ) , breast cancer, triple negative ( 3 , 12 ) , colorectal cancer ( 4 ) , colorectal carcinoma ( 4 ) , liver cancer ( 5 ) , hepatocellular carcinoma ( 5 ) , lung cancer ( 15 ) , non-small cell lung cancer ( 15 ) , non-small cell lung adenocarcinoma ( 15 ) , prostate cancer ( 1 , 14 , 18 )
Relevant cell line - cell type - tissue:	293 (epithelial) ( 11 ) , A172 (glial) ( 13 ) , A549 (pulmonary) ( 15 ) , breast ( 12 ) , COLO-201 (intestinal) ( 4 ) , COLO-205 (intestinal) ( 4 ) , DU 145 (prostate cell) ( 1 , 14 ) , fibroblast-foreskin ( 19 ) , HaCaT (keratinocyte) ( 6 ) , HCC1806 (breast cell) ( 3 ) , HEK293T (epithelial) ( 3 , 15 ) , HeLa (cervical) ( 7 , 18 , 20 , 21 ) , HeLa S3 (cervical) ( 24 ) , HLE (hepatic) ( 5 ) , HT-29 (intestinal) ( 4 ) , Jurkat (T lymphocyte) ( 23 ) , JY (lymphoblastoid) ( 16 ) , Ker-CT ( 6 ) , kidney ( 2 ) , LN18 (glial) ( 13 ) , LN229 (glial) ( 13 ) , LNCaP (prostate cell) ( 18 ) , LoVo (intestinal) ( 4 ) , MCF-7 (breast cell) ( 22 ) , MDA-MB-231 (breast cell) ( 3 , 10 ) , MEF (fibroblast) ( 8 ) , T47D (breast cell) ( 25 ) , U2OS (bone cell) ( 3 , 9 ) , U87MG (glial) ( 13 )

Upstream Regulation
Regulatory protein:	CASP2 (human) ( 8 ) , CRYAB (human) ( 5 ) , FBXO44 (human) ( 10 ) , iNOS (human) ( 7 ) , POLK (human) ( 13 ) , SAMHD1 (human) ( 9 ) , SETD2 (human) ( 2 )
Kinases, in vitro:	CDK1 (human) ( 15 )
Treatments:	arsenic ( 6 ) , CCT007093 ( 18 ) , galiellalactone ( 14 ) , hydroxyurea ( 8 ) , ionizing_radiation ( 18 , 22 ) , okadaic_acid ( 22 ) , oxaliplatin ( 4 ) , rabusertib ( 2 ) , THIF ( 25 ) , TMZ removal ( 13 ) , UV ( 5 , 15 ) , VE822 ( 2 ) , virus infection ( 7 )

Downstream Regulation
Effects of modification on ATR:	activity, induced ( 3 ) , enzymatic activity, induced ( 5 , 25 ) , intracellular localization ( 16 ) , molecular association, regulation ( 15 ) , phosphorylation ( 5 ) , ubiquitination ( 3 )
Effects of modification on biological processes:	apoptosis, induced ( 5 ) , cell cycle regulation ( 9 , 16 ) , cell growth, altered ( 25 ) , cell growth, induced ( 16 ) , DNA repair, induced ( 3 , 8 ) , DNA repair, inhibited ( 16 ) , transcription, altered ( 5 )
Induce interaction with:	BID (human) ( 15 ) , PIN1 (human) ( 15 )

Disease / Diagnostics Relevance
Relevant diseases:	colorectal carcinoma ( 4 )

References
1	Chao Y, et al. (2024) Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer. Oncogene 38273024 Curated Info
2	Liu XD, et al. (2023) SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma. Clin Cancer Res 29, 4002-4015 37527013 Curated Info
3	Liu W, et al. (2023) RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy. Adv Sci (Weinh) 10, e2203884 36563124 Curated Info
4	Hsieh CC, et al. (2022) CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer. Br J Cancer 35999268 Curated Info
5	Xiao Y, et al. (2022) MAB21L1 promotes survival of lens epithelial cells through control of αB-crystallin and ATR/CHK1/p53 pathway. Aging (Albany NY) 14, 6128-6148 35951367 Curated Info
6	Nail AN, et al. (2022) Chronic arsenic exposure suppresses ATM pathway activation in human keratinocytes. Toxicol Appl Pharmacol 446, 116042 35513056 Curated Info
7	Wang F, et al. (2022) Cytoplasmic PARP1 links the genome instability to the inhibition of antiviral immunity through PARylating cGAS. Mol Cell 35460603 Curated Info
8	Boice AG, et al. (2021) Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis. Oncogene 34718349 Curated Info
9	Park K, et al. (2021) Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription-replication conflict regions. PLoS Genet 17, e1009523 33857133 Curated Info
10	Shen JZ, et al. (2021) FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells. Cell 184, 352-369.e23 33357448 Curated Info
11	Hamperl S, et al. (2017) Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses. Cell 170, 774-786.e19 28802045 Curated Info
12	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
13	Peng C, et al. (2016) The Error-Prone DNA Polymerase κ Promotes Temozolomide Resistance in Glioblastoma through Rad17-Dependent Activation of ATR-Chk1 Signaling. Cancer Res 76, 2340-53 26960975 Curated Info
14	García V, et al. (2016) Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells. Oncotarget 7, 4490-506 26683224 Curated Info
15	Hilton BA, et al. (2015) ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1. Mol Cell 60, 35-46 26387736 Curated Info
16	Koganti S, et al. (2014) STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation. Proc Natl Acad Sci U S A 111, 4946-51 24639502 Curated Info
17	Yang X, et al. (2013) Histone acetyltransferase 1 promotes homologous recombination in DNA repair by facilitating histone turnover. J Biol Chem 288, 18271-82 23653357 Curated Info
18	Song JY, et al. (2013) Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to γ-radiation. Cell Death Dis 4, e744 23907458 Curated Info
19	Lossaint G, et al. (2011) Chk1 is dispensable for G2 arrest in response to sustained DNA damage when the ATM/p53/p21 pathway is functional. Oncogene 30, 4261-74 21532626 Curated Info
20	Nam EA, et al. (2011) Thr-1989 Phosphorylation Is a Marker of Active Ataxia Telangiectasia-mutated and Rad3-related (ATR) Kinase. J Biol Chem 286, 28707-14 21705319 Curated Info
21	Kettenbach AN, et al. (2011) Quantitative phosphoproteomics identifies substrates and functional modules of aurora and polo-like kinase activities in mitotic cells. Sci Signal 4, rs5 21712546 Curated Info
22	Yan Y, et al. (2010) Protein phosphatase 2A has an essential role in the activation of gamma-irradiation-induced G2/M checkpoint response. Oncogene 29, 4317-29 20498628 Curated Info
23	Possemato A (2008) CST Curation Set: 5689; Year: 2008; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS/T) Immunoaffinity Beads Cat#: 1978 Curated Info
24	Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48 18691976 Curated Info
25	Vauzour D, et al. (2007) Inhibition of cellular proliferation by the genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathway. Arch Biochem Biophys 468, 159-66 17976513 Curated Info