Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKMW34I)

• DOT Name: SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3)
• Synonyms: SH3 domain-binding protein 1; SH3BP-1; TNF inhibitory protein B1; TIP-B1
• Gene Name: SH3BGRL3
• Related Disease:
  Thyroid gland papillary carcinoma
  Advanced cancer
  Bladder cancer
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Neoplasm
  Systemic lupus erythematosus
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Clear cell renal carcinoma
• UniProt ID: SH3L3_HUMAN
• PDB ID: 1SJ6
• Pfam ID: PF04908
• Sequence:
  MSGLRVYSTSVTGSREIKSQQSEVTRILDGKRIQYQLVDISQDNALRDEMRALAGNPKAT
  PPQIVNGDQYCGDYELFVEAVEQNTLQEFLKLA
• Function: Could act as a modulator of glutaredoxin biological activity (Probable). May play a role in cytoskeleton organization.
• Tissue Specificity: Ubiquitous . Expressed in heart, kidney and liver (at protein level) . Expressed in brain, lung, spleen and skeletal muscle .

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[6]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[2]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3) affects the response to substance of Cisplatin.	[21]
Methotrexate	DM2TEOL	Approved	SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3) affects the response to substance of Methotrexate.	[21]

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 SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[19]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3).	[20]

References

• [1] Integrated analysis of fine-needle-aspiration cystic fluid proteome, cancer cell secretome, and public transcriptome datasets for papillary thyroid cancer biomarker discovery.Oncotarget. 2018 Jan 4;9(15):12079-12100. doi: 10.18632/oncotarget.23951. eCollection 2018 Feb 23.
• [2] SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma: A Novel Binding Partner of Epidermal Growth Factor Receptor.Clin Cancer Res. 2015 Dec 15;21(24):5601-11. doi: 10.1158/1078-0432.CCR-14-3308. Epub 2015 Aug 18.
• [3] SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway.Oncotarget. 2016 Apr 5;7(14):18356-70. doi: 10.18632/oncotarget.7786.
• [4] Identification of urine biomarkers associated with lung adenocarcinoma.Oncotarget. 2017 Jun 13;8(24):38517-38529. doi: 10.18632/oncotarget.15870.
• [5] TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.Aging (Albany NY). 2019 Sep 27;11(18):7914-7937. doi: 10.18632/aging.102298. Epub 2019 Sep 27.
• [6] Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.Mol Immunol. 2006 Mar;43(9):1497-507. doi: 10.1016/j.molimm.2005.07.039. Epub 2005 Sep 6.
• [7] 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.
• [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] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [18] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [19] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [20] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.