Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUBTU57)

• DOT Name: Rho-related GTP-binding protein RhoQ (RHOQ)
• Synonyms: Ras-like protein TC10; Ras-like protein family member 7A
• Gene Name: RHOQ
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Neoplasm
  Chronic obstructive pulmonary disease
• UniProt ID: RHOQ_HUMAN
• PDB ID: 2ATX
• Pfam ID: PF00071
• Sequence:
  MAHGPGALMLKCVVVGDGAVGKTCLLMSYANDAFPEEYVPTVFDHYAVSVTVGGKQYLLG
  LYDTAGQEDYDRLRPLSYPMTDVFLICFSVVNPASFQNVKEEWVPELKEYAPNVPFLLIG
  TQIDLRDDPKTLARLNDMKEKPICVEQGQKLAKEIGACCYVECSALTQKGLKTVFDEAII
  AILTPKKHTVKKRIGSRCINCCLIT
• Function: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. May play a role in CFTR trafficking to the plasma membrane. Causes the formation of thin, actin-rich surface projections called filopodia.
• KEGG Pathway: Insulin sig.ling pathway (hsa04910)
• Reactome Pathway:
  RHO GTPases regulate CFTR trafficking (R-HSA-5627083)
  RHOQ GTPase cycle (R-HSA-9013406)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[4]

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 Rho-related GTP-binding protein RhoQ (RHOQ).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Rho-related GTP-binding protein RhoQ (RHOQ).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Rho-related GTP-binding protein RhoQ (RHOQ).	[19]

17 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 Rho-related GTP-binding protein RhoQ (RHOQ).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[21]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate affects the expression of Rho-related GTP-binding protein RhoQ (RHOQ).	[22]

References

• [1] RNA editing in RHOQ promotes invasion potential in colorectal cancer.J Exp Med. 2014 Apr 7;211(4):613-21. doi: 10.1084/jem.20132209. Epub 2014 Mar 24.
• [2] Silencing of D4-GDI inhibits growth and invasive behavior in MDA-MB-231 cells by activation of Rac-dependent p38 and JNK signaling.J Biol Chem. 2009 May 8;284(19):12956-65. doi: 10.1074/jbc.M807845200. Epub 2009 Mar 6.
• [3] Development of (99m)Tc-labeled trivalent isonitrile radiotracer for folate receptor imaging.Bioorg Med Chem. 2019 May 15;27(10):1925-1931. doi: 10.1016/j.bmc.2019.04.013. Epub 2019 Apr 10.
• [4] Roles of Myeloid and Lymphoid Cells in the Pathogenesis of Chronic Obstructive Pulmonary Disease.Front Immunol. 2018 Jun 21;9:1431. doi: 10.3389/fimmu.2018.01431. 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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [11] 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.
• [12] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] 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.
• [19] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Molecular mechanism of di-n-butyl phthalate promotion of bladder cancer development. Toxicol In Vitro. 2023 Feb;86:105508. doi: 10.1016/j.tiv.2022.105508. Epub 2022 Nov 12.