Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT13LJ1A)

• DOT Name: SH3 domain-binding glutamic acid-rich protein (SH3BGR)
• Synonyms: SH3BGR protein; 21-glutamic acid-rich protein; 21-GARP
• Gene Name: SH3BGR
• Related Disease: Congenital heart disease
• UniProt ID: SH3BG_HUMAN
• Pfam ID: PF04908
• Sequence:
  MPLLLLGETEPLKLERDCRSPVDPWAAASPDLALACLCHCQDLSSGAFPDRGVLGGVLFP
  TVEMVIKVFVATSSGSIAIRKKQQEVVGFLEANKIDFKELDIAGDEDNRRWMRENVPGEK
  KPQNGIPLPPQIFNEEQYCGDFDSFFSAKEENIIYSFLGLAPPPDSKGSEKAEEGGETEA
  QKEGSEDVGNLPEAQEKNEEEGETATEETEEIAMEGAEGEAEEEEETAEGEEPGEDEDS
• Tissue Specificity: Expressed in heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[1]

12 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-binding glutamic acid-rich protein (SH3BGR).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[13]

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 SH3 domain-binding glutamic acid-rich protein (SH3BGR).	[11]

References

• [1] High-resolution physical map and identification of potentially regulatory sequences of the human SH3BGR located in the Down syndrome chromosomal region.Biochem Biophys Res Commun. 1997 Dec 18;241(2):321-6. doi: 10.1006/bbrc.1997.7816.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [6] 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.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [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.
• [13] Global gene expression analysis reveals novel transcription factors associated with long-term low-level exposure of EA.hy926 human endothelial cells to bisphenol A. Chem Biol Interact. 2023 Aug 25;381:110571. doi: 10.1016/j.cbi.2023.110571. Epub 2023 May 25.