Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGTHL5V)

• DOT Name: SH2 domain-containing adapter protein D (SHD)
• Gene Name: SHD
• UniProt ID: SHD_HUMAN
• Pfam ID: PF00017
• Sequence:
  MAKWLRDYLSFGGRRPPPQPPTPDYTESDILRAYRAQKNLDFEDPYEDAESRLEPDPAGP
  GDSKNPGDAKYGSPKHRLIKVEAADMARAKALLGGPGEELEADTEYLDPFDAQPHPAPPD
  DGYMEPYDAQWVMSELPGRGVQLYDTPYEEQDPETADGPPSGQKPRQSRMPQEDERPADE
  YDQPWEWKKDHISRAFAVQFDSPEWERTPGSAKELRRPPPRSPQPAERVDPALPLEKQPW
  FHGPLNRADAESLLSLCKEGSYLVRLSETNPQDCSLSLRSSQGFLHLKFARTRENQVVLG
  QHSGPFPSVPELVLHYSSRPLPVQGAEHLALLYPVVTQTP
• Function: May function as an adapter protein.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of SH2 domain-containing adapter protein D (SHD).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SH2 domain-containing adapter protein D (SHD).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH2 domain-containing adapter protein D (SHD).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SH2 domain-containing adapter protein D (SHD).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of SH2 domain-containing adapter protein D (SHD).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SH2 domain-containing adapter protein D (SHD).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SH2 domain-containing adapter protein D (SHD).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SH2 domain-containing adapter protein D (SHD).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of SH2 domain-containing adapter protein D (SHD).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of SH2 domain-containing adapter protein D (SHD).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of SH2 domain-containing adapter protein D (SHD).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SH2 domain-containing adapter protein D (SHD).	[12]

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 increases the methylation of SH2 domain-containing adapter protein D (SHD).	[11]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.