Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOX4XT7)

• DOT Name: SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2)
• Synonyms: Fovea-associated SH3 domain-binding protein
• Gene Name: SH3BGRL2
• Related Disease: Juvenile idiopathic arthritis
• UniProt ID: SH3L2_HUMAN
• PDB ID: 2CT6
• Pfam ID: PF04908
• Sequence:
  MVIRVFIASSSGFVAIKKKQQDVVRFLEANKIEFEEVDITMSEEQRQWMYKNVPPEKKPT
  QGNPLPPQIFNGDRYCGDYDSFFESKESNTVFSFLGLKPRLASKAEP
• Tissue Specificity: Highly expressed in brain, placenta, liver and kidney. Expressed in retina.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[9]

8 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 SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[7]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2).	[11]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [8] 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.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.