Thr21
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Home > Phosphorylation Site Page: > Thr21  -  RFA2 (human)

Site Information
yGGAGGYtQsPGGFG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448340

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 17 , 19 ) , electrophoretic mobility shift ( 16 , 19 ) , flow cytometry ( 15 ) , immunoassay ( 2 , 5 , 9 ) , immunoprecipitation ( 5 , 10 , 12 ) , mutation of modification site ( 4 , 5 , 10 , 13 , 15 , 16 ) , peptide sequencing ( 19 ) , phospho-antibody ( 2 , 3 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 17 ) , phosphoamino acid analysis ( 18 ) , phosphopeptide mapping ( 19 ) , western blotting ( 2 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 , 18 )
Disease tissue studied:
ataxia-telangiectasia ( 17 , 18 ) , bone cancer ( 5 , 7 , 9 , 11 , 12 , 13 , 15 , 16 ) , brain cancer ( 17 ) , glioblastoma ( 17 ) , glioma ( 17 ) , breast cancer ( 2 , 7 ) , liver cancer ( 12 ) , lung cancer ( 5 , 12 ) , non-small cell lung cancer ( 5 ) , non-small cell lung adenocarcinoma ( 5 ) , ovarian cancer ( 3 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
ATM (human) ( 5 ) , ATR (human) ( 5 , 8 ) , BAT1 (human) ( 3 ) , CDC5L (human) ( 8 ) , CLK2 (human) ( 14 ) , CtIP (human) ( 8 ) , FAAP24 (human) ( 14 ) , FANCM (human) ( 14 ) , FBXO44 (human) ( 2 ) , p21Cip1 (human) ( 5 ) , p53 (human) ( 5 ) , PRPF19 (human) ( 8 ) , PRPF3 (human) ( 8 ) , SUV39H1 (human) ( 2 ) , TOPBP1 (human) ( 7 )
Putative in vivo kinases:
ATM (human) ( 17 ) , DNAPK (human) ( 15 , 17 )
Kinases, in vitro:
ATM (human) ( 17 ) , ATR (human) ( 16 ) , DNAPK (human) ( 17 , 19 , 20 )
Putative upstream phosphatases:
PPP2CA (human) ( 12 ) , PPP4C (human) ( 11 )
Treatments:
adriamycin ( 17 ) , aphidicolin ( 17 ) , AZ20 ( 9 ) , caffeine ( 12 , 17 , 18 ) , camptothecin ( 5 , 8 , 17 , 18 ) , CPT ( 3 , 15 ) , Et743 ( 6 ) , etoposide ( 17 ) , hydroxyurea ( 9 , 12 , 13 ) , ionizing_radiation ( 17 ) , lurbinectedin ( 6 ) , okadaic_acid ( 12 ) , olaparib ( 7 ) , release from HU ( 12 ) , release_from_UV ( 12 ) , seliciclib ( 14 , 15 ) , siRNA ( 14 ) , t-BH ( 17 ) , UV ( 12 , 17 , 19 ) , wortmannin ( 17 , 18 )

Downstream Regulation
Effects of modification on RFA2:
intracellular localization ( 12 , 16 ) , molecular association, regulation ( 5 , 10 ) , phosphorylation ( 16 )
Effects of modification on biological processes:
apoptosis, altered ( 13 ) , cell cycle regulation ( 5 , 13 ) , cell growth, altered ( 16 ) , DNA repair, induced ( 3 , 5 , 10 ) , transcription, altered ( 5 )
Induce interaction with:
WRN (human) ( 10 ) , p53 (human) ( 5 )

References 

1

Devin J, et al. (2022) Targeting cellular iron homeostasis with ironomycin in diffuse large B cell lymphoma. Cancer Res
35078814   Curated Info

2

Shen JZ, et al. (2021) FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells. Cell 184, 352-369.e23
33357448   Curated Info

3

Xu Z, et al. (2020) Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA. Oncogene
32989256   Curated Info

4

Liu L, et al. (2019) O-GlcNAcylation of Thr12 / Ser56 in short form O-GlcNAc transferase (sOGT) regulates its substrate selectivity. J Biol Chem
31527085   Curated Info

5

Romanova LY, Mushinski F, Kovalchuk AL (2018) Transcriptional activation of p21 contributes to suppression of HR by p53 in response to replication arrest induced by camptothecin. Oncotarget 9, 25427-25440
29875999   Curated Info

6

Lima M, et al. (2016) Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair. Oncotarget 7, 25885-901
27029031   Curated Info

7

Moudry P, et al. (2016) TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. J Cell Biol 212, 281-8
26811421   Curated Info

8

Maréchal A, et al. (2014) PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry. Mol Cell 53, 235-46
24332808   Curated Info

9

Toledo LI, et al. (2013) ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA. Cell 155, 1088-103
24267891   Curated Info

10

Machwe A, et al. (2011) Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage. J Biol Chem 286, 3497-508
21107010   Curated Info

11

Lee DH, et al. (2010) A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol 17, 365-72
20154705   Curated Info

12

Feng J, et al. (2009) Protein phosphatase 2A-dependent dephosphorylation of replication protein A is required for the repair of DNA breaks induced by replication stress. Mol Cell Biol 29, 5696-709
19704001   Curated Info

13

Vassin VM, et al. (2009) Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress. J Cell Sci 122, 4070-80
19843584   Curated Info

14

Collis SJ, et al. (2008) FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Mol Cell 32, 313-24
18995830   Curated Info

15

Anantha RW, Vassin VM, Borowiec JA (2007) Sequential and Synergistic Modification of Human RPA Stimulates Chromosomal DNA Repair. J Biol Chem 282, 35910-23
17928296   Curated Info

16

Olson E, et al. (2006) RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint. J Biol Chem 281, 39517-33
17035231   Curated Info

17

Block WD, Yu Y, Lees-Miller SP (2004) Phosphatidyl inositol 3-kinase-like serine/threonine protein kinases (PIKKs) are required for DNA damage-induced phosphorylation of the 32 kDa subunit of replication protein A at threonine 21. Nucleic Acids Res 32, 997-1005
14872059   Curated Info

18

Block WD, Merkle D, Meek K, Lees-Miller SP (2004) Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine. Nucleic Acids Res 32, 1967-72
15060176   Curated Info

19

Zernik-Kobak M, et al. (1997) Sites of UV-induced phosphorylation of the p34 subunit of replication protein A from HeLa cells. J Biol Chem 272, 23896-904
9295339   Curated Info

20

Niu H, et al. (1997) Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro. J Biol Chem 272, 12634-41
9139719   Curated Info