Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6CH5UO)

• DOT Name: DNA repair protein SWI5 homolog (SWI5)
• Synonyms: HBV DNAPTP1-transactivated protein A; Protein SAE3 homolog
• Gene Name: SWI5
• UniProt ID: SWI5_HUMAN
• Pfam ID: PF07061
• Sequence:
  MQRRGQRDLWRHNKSCARNRCPRPPRERGGAGFPWVRAQLSVRQFTLRVRVPGPVHLRGR
  SPTPALDPLAPLNPLIRGPRTPGLRRWIQSLALLLPNCSSSRIPTVPRPHSGLWVQSDFP
  LGFLSRTEPRLTRSCRGAFRSPRPLPKSGQADGTSEESLHLDIQKLKEKRDMLDKEISQF
  VSEGYSVDELEDHITQLHEYNDIKDVGQMLMGKLAVIRGVTTKELYPEFGLDMND
• Function: Component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	DNA repair protein SWI5 homolog (SWI5) affects the response to substance of Acetaminophen.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DNA repair protein SWI5 homolog (SWI5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA repair protein SWI5 homolog (SWI5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA repair protein SWI5 homolog (SWI5).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DNA repair protein SWI5 homolog (SWI5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA repair protein SWI5 homolog (SWI5).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of DNA repair protein SWI5 homolog (SWI5).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DNA repair protein SWI5 homolog (SWI5).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA repair protein SWI5 homolog (SWI5).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of DNA repair protein SWI5 homolog (SWI5).	[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 affects the methylation of DNA repair protein SWI5 homolog (SWI5).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.