Details of Drug Off-Target (DOT)

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

• DOT Name: Sushi domain-containing protein 3 (SUSD3)
• Gene Name: SUSD3
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: SUSD3_HUMAN
• Pfam ID: PF00084
• Sequence:
  MRWAAATLRGKARPRGRAGVTTPAPGNRTGTCAKLRLPPQATFQVLRGNGASVGTVLMFR
  CPSNHQMVGSGLLTCTWKGSIAEWSSGSPVCKLVPPHETFGFKVAVIASIVSCAIILLMS
  MAFLTCCLLKCVKKSKRRRSNRSAQLWSQLKDEDLETVQAAYLGLKHFNKPVSGPSQAHD
  NHSFTTDHGESTSKLASVTRSVDKDPGIPRALSLSGSSSSPQAQVMVHMANPRQPLPASG
  LATGMPQQPAAYALG
• Function: May play a role in breast tumorigenesis by promoting estrogen-dependent cell proliferation, cell-cell interactions and migration.
• Tissue Specificity: Highly expressed in estrogen receptor-positive breast tumors.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sushi domain-containing protein 3 (SUSD3).	[2]

14 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 Sushi domain-containing protein 3 (SUSD3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sushi domain-containing protein 3 (SUSD3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sushi domain-containing protein 3 (SUSD3).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sushi domain-containing protein 3 (SUSD3).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sushi domain-containing protein 3 (SUSD3).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sushi domain-containing protein 3 (SUSD3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sushi domain-containing protein 3 (SUSD3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Sushi domain-containing protein 3 (SUSD3).	[13]

References

• [1] Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells.Oncogene. 2015 Jan 15;34(3):323-33. doi: 10.1038/onc.2013.553. Epub 2014 Jan 13.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.