Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNUAIO9)

• DOT Name: Transcriptional adapter 3 (TADA3)
• Synonyms: ADA3 homolog; hADA3; STAF54; Transcriptional adapter 3-like; ADA3-like protein
• Gene Name: TADA3
• Related Disease:
  Breast neoplasm
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Neoplasm
  Non-small-cell lung cancer
  Breast cancer
  Breast carcinoma
  Estrogen-receptor positive breast cancer
  Advanced cancer
• UniProt ID: TADA3_HUMAN
• Pfam ID: PF10198
• Sequence:
  MSELKDCPLQFHDFKSVDHLKVCPRYTAVLARSEDDGIGIEELDTLQLELETLLSSASRR
  LRVLEAETQILTDWQDKKGDRRFLKLGRDHELGAPPKHGKPKKQKLEGKAGHGPGPGPGR
  PKSKNLQPKIQEYEFTDDPIDVPRIPKNDAPNRFWASVEPYCADITSEEVRTLEELLKPP
  EDEAEHYKIPPLGKHYSQRWAQEDLLEEQKDGARAAAVADKKKGLMGPLTELDTKDVDAL
  LKKSEAQHEQPEDGCPFGALTQRLLQALVEENIISPMEDSPIPDMSGKESGADGASTSPR
  NQNKPFSVPHTKSLESRIKEELIAQGLLESEDRPAEDSEDEVLAELRKRQAELKALSAHN
  RTKKHDLLRLAKEEVSRQELRQRVRMADNEVMDAFRKIMAARQKKRTPTKKEKDQAWKTL
  KERESILKLLDG
• Function: Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex. Also known as a coactivator for p53/TP53-dependent transcriptional activation. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  Ub-specific processing proteases (R-HSA-5689880)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[2]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Disputed	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcriptional adapter 3 (TADA3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcriptional adapter 3 (TADA3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcriptional adapter 3 (TADA3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transcriptional adapter 3 (TADA3).	[9]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transcriptional adapter 3 (TADA3).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transcriptional adapter 3 (TADA3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcriptional adapter 3 (TADA3).	[12]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Transcriptional adapter 3 (TADA3).	[13]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transcriptional adapter 3 (TADA3).	[11]

References

• [1] Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent breast cancer cell proliferation.Cancer Res. 2007 Dec 15;67(24):11789-97. doi: 10.1158/0008-5472.CAN-07-2721.
• [2] Epidermal Growth Factor Receptor activation promotes ADA3 acetylation through the AKT-p300 pathway.Cell Cycle. 2017 Aug 18;16(16):1515-1525. doi: 10.1080/15384101.2017.1339846. Epub 2017 Jul 31.
• [3] ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC.Breast Cancer Res. 2016 Nov 16;18(1):113. doi: 10.1186/s13058-016-0770-9.
• [4] Overexpression of Alteration/Deficiency in Activation 3 correlates with poor prognosis in non-small cell lung cancer.Pathol Res Pract. 2019 Jun;215(6):152408. doi: 10.1016/j.prp.2019.03.036. Epub 2019 Apr 2.
• [5] Tale of a multifaceted co-activator, hADA3: from embryogenesis to cancer and beyond.Open Biol. 2016 Sep;6(9):160153. doi: 10.1098/rsob.160153.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability. Int J Mol Sci. 2023 Mar 15;24(6):5604. doi: 10.3390/ijms24065604.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Fermentation Extract of Naringenin Increases the Expression of Estrogenic Receptor and Modulates Genes Related to the p53 Signalling Pathway, miR-200c and miR-141 in Human Colon Cancer Cells Exposed to BPA. Molecules. 2022 Oct 5;27(19):6588. doi: 10.3390/molecules27196588.
• [13] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.