Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVU3VS2)

• DOT Name: SH3 domain-containing protein 19 (SH3D19)
• Synonyms: ADAM-binding protein Eve-1; EEN-binding protein; EBP
• Gene Name: SH3D19
• UniProt ID: SH319_HUMAN
• Pfam ID: PF00018 ; PF07653 ; PF14604
• Sequence:
  MNIMNTEQSQNSIVSRIKVFEGQTNIETSGLPKKPEITPRSLPPKPTVSSGKPSVAPKPA
  ANRASGEWDSGTENRLKVTSKEGLTPYPPLQEAGSIPVTKPELPKKPNPGLIRSVNPEIP
  GRGPLAESSDSGKKVPTPAPRPLLLKKSVSSENPTYPSAPLKPVTVPPRLAGASQAKAYK
  SLGEGPPANPPVPVLQSKPLVDIDLISFDDDVLPTPSGNLAEESVGSEMVLDPFQLPAKT
  EPIKERAVQPAPTRKPTVIRIPAKPGKCLHEDPQSPPPLPAEKPIGNTFSTVSGKLSNVE
  RTRNLESNHPGQTGGFVRVPPRLPPRPVNGKTIPTQQPPTKVPPERPPPPKLSATRRSNK
  KLPFNRSSSDMDLQKKQSNLATGLSKAKSQVFKNQDPVLPPRPKPGHPLYSKYMLSVPHG
  IANEDIVSQNPGELSCKRGDVLVMLKQTENNYLECQKGEDTGRVHLSQMKIITPLDEHLR
  SRPNDPSHAQKPVDSGAPHAVVLHDFPAEQVDDLNLTSGEIVYLLEKIDTDWYRGNCRNQ
  IGIFPANYVKVIIDIPEGGNGKRECVSSHCVKGSRCVARFEYIGEQKDELSFSEGEIIIL
  KEYVNEEWARGEVRGRTGIFPLNFVEPVEDYPTSGANVLSTKVPLKTKKEDSGSNSQVNS
  LPAEWCEALHSFTAETSDDLSFKRGDRIQILERLDSDWCRGRLQDREGIFPAVFVRPCPA
  EAKSMLAIVPKGRKAKALYDFRGENEDELSFKAGDIITELESVDDDWMSGELMGKSGIFP
  KNYIQFLQIS
• Function: May play a role in regulating A disintegrin and metalloproteases (ADAMs) in the signaling of EGFR-ligand shedding. May be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1. Plays a role in the regulation of cell morphology and cytoskeletal organization.
• Tissue Specificity: Widely expressed with highest levels in heart, skeletal muscle, kidney, liver, placenta, small intestine and lung. Expressed at low levels in colon, thymus, spleen and leukocytes.
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

18 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 SH3 domain-containing protein 19 (SH3D19).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SH3 domain-containing protein 19 (SH3D19).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH3 domain-containing protein 19 (SH3D19).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of SH3 domain-containing protein 19 (SH3D19).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of SH3 domain-containing protein 19 (SH3D19).	[13]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of SH3 domain-containing protein 19 (SH3D19).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SH3 domain-containing protein 19 (SH3D19).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SH3 domain-containing protein 19 (SH3D19).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of SH3 domain-containing protein 19 (SH3D19).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of SH3 domain-containing protein 19 (SH3D19).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SH3 domain-containing protein 19 (SH3D19).	[15]

References

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• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] 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.
• [14] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [15] 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.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [19] 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.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.