Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHFX32I)

DOT Name Ewing's tumor-associated antigen 1 (ETAA1)
Synonyms Ewing's tumor-associated antigen 16
Gene Name ETAA1
Related Disease
Chromosomal disorder ( )
Pancreatic tumour ( )
Lung carcinoma ( )
UniProt ID
ETAA1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8JZV
Pfam ID
PF15350
Sequence
MSRRRKHDDSPSPKKTPHKTVAAEECGSVVEPGRRRLRSARGSWPCGAREGPPGPVRQRE
QPPTAALCSKSNPEERYETPKRALKMDSLSSSFSSPNDPDGQNDIFWDQNSPLTKQLGKG
RKKQIYTTDSDEISHIVNRIAPQDEKPTTNSMLDMWIGETAIPCTPSVAKGKSRAKISCT
KLKTQSQEEELMKLAKQFDKNMEELDVIQEQNKRNYDFTQMISETEILSNYKDNIQMWSL
HNIVPEIDNATKKPIKGNTKISVANNQNSSQKPFDQIAEAAFNAIFDGSTQKCSGQLSQE
LPEAFWSTSNTTFVKTNALKEEKIITNETLVIEKLSNKTPRSLSSQVDTPIMTKSCVTSC
TKEPETSNKYIDAFTTSDFEDDWENLLGSEPFAMQNIDMPELFPSKTAHVTDQKEICTFN
SKTVKNTSRANTSPDARLGDSKVLQDLSSKTYDRELIDAEYRFSPNSNKSNKLSTGNKMK
FENSSNKIVIQDEIQNCIVTSNLTKIKEDILTNSTEASERKSALNTRYSNEQKNKCILNQ
SIKAPVNTDLFGSANLGSKTSVSNPNQTSASKVGSFFDDWNDPSFANEIIKACHQLDNTW
EADDVDDDLLYQACDDIERLTQQQDIRKDSKTSESICEINNNSEHGAKLTQQQDIRKDSK
TSESICEINNNSEHGAKNMFAISKQGSNLVQSKHLNPGSISVQTSLTNSSQIDKPMKMEK
GEMYGNSPRFLGATNLTMYSKISNCQINNLHVSYTNTDVPIQVNSSKLVLPGSSSLNVTS
DHMNTEITTYKKKLSTNQPCHKTVTDEAQSNLNTTVGFSKFTFTRMKNSQILSQFNQNCI
TGSMSDTKITQGVEKKKGVNPLLEEAVGQQSLVKLSESLKQSSKEEEEKNRKCSPEEIQR
KRQEALVRRMAKARASSVNAAPTSFL
Function
Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity. Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1. Probably only regulates a subset of ATR targets.
Tissue Specificity Expressed at high levels in the brain, liver kidney and Ewing tumor cell lines.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chromosomal disorder DISM5BB5 Strong Biomarker [1]
Pancreatic tumour DIS3U0LK Strong Biomarker [2]
Lung carcinoma DISTR26C Limited Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Ewing's tumor-associated antigen 1 (ETAA1). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Ewing's tumor-associated antigen 1 (ETAA1). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Ewing's tumor-associated antigen 1 (ETAA1). [6]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Ewing's tumor-associated antigen 1 (ETAA1). [7]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Ewing's tumor-associated antigen 1 (ETAA1). [8]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Ewing's tumor-associated antigen 1 (ETAA1). [9]
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⏷ Show the Full List of 6 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Ewing's tumor-associated antigen 1 (ETAA1). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Ewing's tumor-associated antigen 1 (ETAA1). [11]
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References

1 Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability.J Cell Biol. 2019 Dec 2;218(12):3943-3953. doi: 10.1083/jcb.201905064. Epub 2019 Oct 15.
2 Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.Nat Genet. 2015 Aug;47(8):911-6. doi: 10.1038/ng.3341. Epub 2015 Jun 22.
3 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
8 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.