Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQP9BWM)

• DOT Name: SERTA domain-containing protein 3 (SERTAD3)
• Synonyms: Replication protein-binding trans-activator; RPA-binding trans-activator
• Gene Name: SERTAD3
• Related Disease: Neoplasm
• UniProt ID: SRTD3_HUMAN
• Pfam ID: PF06031
• Sequence:
  MVGGLKRKHSDLEEEEERWEWSPAGLQSYQQALLRISLDKVQRSLGPRAPSLRRHVLIHN
  TLQQLQAALRLAPAPALPPEPLFLGEEDFSLSATIGSILRELDTSMDGTEPPQNPVTPLG
  LQNEVPPQPDPVFLEALSSRYLGDSGLDDFFLDIDTSAVEKEPARAPPEPPHNLFCAPGS
  WEWNELDHIMEIILGS
• Function: Antiviral interferon-stimulated protein that plays a role in innate immunity and in the suppression of viruses through different mechanisms. Plays a role in the late phase response of TLR-induced immune effector expression. During influenza infection, interacts with PB2, PB1, and PA to disrupt the formation of the viral RdRp complex. Inhibits zika virus by interacting with the capsid protein in the nucleolus and reducing its abundance through proteasomal degradation. Strong transcriptional coactivator.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Disputed	Biomarker	[1]

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 SERTA domain-containing protein 3 (SERTAD3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SERTA domain-containing protein 3 (SERTAD3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SERTA domain-containing protein 3 (SERTAD3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SERTA domain-containing protein 3 (SERTAD3).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of SERTA domain-containing protein 3 (SERTAD3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SERTA domain-containing protein 3 (SERTAD3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of SERTA domain-containing protein 3 (SERTAD3).	[9]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of SERTA domain-containing protein 3 (SERTAD3).	[10]

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 decreases the methylation of SERTA domain-containing protein 3 (SERTAD3).	[7]

References

• [1] Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth.Oncogene. 2007 Jun 21;26(29):4319-28. doi: 10.1038/sj.onc.1210195. Epub 2007 Jan 29.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [7] 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.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.