Details of Drug Off-Target (DOT)

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

• DOT Name: Adapter SH3BGRL (SH3BGRL)
• Synonyms: SH3 domain-binding glutamic acid-rich-like protein 1
• Gene Name: SH3BGRL
• Related Disease:
  Acute myelogenous leukaemia
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Metastatic malignant neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: SH3L1_HUMAN
• PDB ID: 1U6T; 1WRY
• Pfam ID: PF04908
• Sequence:
  MVIRVYIASSSGSTAIKKKQQDVLGFLEANKIGFEEKDIAANEENRKWMRENVPENSRPA
  TGYPLPPQIFNESQYRGDYDAFFEARENNAVYAFLGLTAPPGSKEAEVQAKQQA
• Function: Appears to function as an adapter protein that bridges proteins together or proteins with mRNAs. May function as a ubiquitin ligase-substrate adapter. Additionally, associates with translating cytoplasmic ribosomes and may promote the expression of specific mRNAs.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Adapter SH3BGRL (SH3BGRL) increases the response to substance of Arsenic trioxide.	[23]

3 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 Adapter SH3BGRL (SH3BGRL).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the methylation of Adapter SH3BGRL (SH3BGRL).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Adapter SH3BGRL (SH3BGRL).	[17]

18 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 Adapter SH3BGRL (SH3BGRL).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adapter SH3BGRL (SH3BGRL).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adapter SH3BGRL (SH3BGRL).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Adapter SH3BGRL (SH3BGRL).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adapter SH3BGRL (SH3BGRL).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Adapter SH3BGRL (SH3BGRL).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adapter SH3BGRL (SH3BGRL).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Adapter SH3BGRL (SH3BGRL).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Adapter SH3BGRL (SH3BGRL).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Adapter SH3BGRL (SH3BGRL).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Adapter SH3BGRL (SH3BGRL).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Adapter SH3BGRL (SH3BGRL).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adapter SH3BGRL (SH3BGRL).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adapter SH3BGRL (SH3BGRL).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Adapter SH3BGRL (SH3BGRL).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adapter SH3BGRL (SH3BGRL).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Adapter SH3BGRL (SH3BGRL).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Adapter SH3BGRL (SH3BGRL).	[11]

References

• [1] SH3BGRL as a novel prognostic biomarker is down-regulated in acute myeloid leukemia.Leuk Lymphoma. 2018 Apr;59(4):918-930. doi: 10.1080/10428194.2017.1344843. Epub 2017 Jul 6.
• [2] Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics.Cancer Genomics Proteomics. 2019 Jul-Aug;16(4):273-286. doi: 10.21873/cgp.20132.
• [3] Dual-faced SH3BGRL: oncogenic in mice, tumor suppressive in humans.Oncogene. 2016 Jun 23;35(25):3303-13. doi: 10.1038/onc.2015.391. Epub 2015 Oct 12.
• [4] Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer.Front Pharmacol. 2018 Aug 3;9:861. doi: 10.3389/fphar.2018.00861. eCollection 2018.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] 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.
• [13] 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.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
• [16] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [17] 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.
• [18] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [19] 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.
• [20] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [21] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.