Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4N3QN)

• DOT Name: Rho-related GTP-binding protein RhoV (RHOV)
• Synonyms: CDC42-like GTPase 2; GTP-binding protein-like 2; Rho GTPase-like protein ARHV; Wnt-1 responsive Cdc42 homolog 2; WRCH-2
• Gene Name: RHOV
• Related Disease:
  Alport syndrome
  Anaplastic large cell lymphoma
  Chronic renal failure
  End-stage renal disease
  Ewing sarcoma
  Focal segmental glomerulosclerosis
  Herpes simplex infection
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Primitive neuroectodermal tumor
  Kidney cancer
  Plasma cell myeloma
  Advanced cancer
  Glomerulonephritis
  Myocardial infarction
  Neoplasm
  Neuroblastoma
  Osteoarthritis
  Parkinson disease
  Pulmonary fibrosis
• UniProt ID: RHOV_HUMAN
• Pfam ID: PF00071
• Sequence:
  MPPRELSEAEPPPLRAPTPPPRRRSAPPELGIKCVLVGDGAVGKSSLIVSYTCNGYPARY
  RPTALDTFSVQVLVDGAPVRIELWDTAGQEDFDRLRSLCYPDTDVFLACFSVVQPSSFQN
  ITEKWLPEIRTHNPQAPVLLVGTQADLRDDVNVLIQLDQGGREGPVPQPQAQGLAEKIRA
  CCYLECSALTQKNLKEVFDSAILSAIEHKARLEKKLNAKGVRTLSRCRWKKFFCFV
• Function: Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway.
• Tissue Specificity: Highly expressed in pancreas, placenta, and fetal brain.
• Reactome Pathway: RHOV GTPase cycle (R-HSA-9013424)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alport syndrome	DIS25AB4	Strong	Biomarker	[1]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Genetic Variation	[2]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[1]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[1]
Ewing sarcoma	DISQYLV3	Strong	Genetic Variation	[3]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[1]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[2]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[6]
Kidney cancer	DISBIPKM	moderate	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[9]
Glomerulonephritis	DISPZIQ3	Limited	Biomarker	[10]
Myocardial infarction	DIS655KI	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[11]
Osteoarthritis	DIS05URM	Limited	Biomarker	[10]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[12]
Pulmonary fibrosis	DISQKVLA	Limited	Biomarker	[10]

3 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 Rho-related GTP-binding protein RhoV (RHOV).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Rho-related GTP-binding protein RhoV (RHOV).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rho-related GTP-binding protein RhoV (RHOV).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[17]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[18]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rho-related GTP-binding protein RhoV (RHOV).	[24]

References

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• [4] Activation of Toll-like receptors inhibits herpes simplex virus-1 infection of human neuronal cells.J Neurosci Res. 2009 Oct;87(13):2916-25. doi: 10.1002/jnr.22110.
• [5] The RHOV gene is overexpressed in human non-small cell lung cancer.Cancer Genet. 2013 Nov;206(11):393-7. doi: 10.1016/j.cancergen.2013.10.006. Epub 2013 Nov 5.
• [6] Caspase inhibition shifts neuroepithelioma cell response to okadaic acid from apoptosis to an apoptotic-like form of death.Biochem Biophys Res Commun. 2003 Apr 4;303(2):469-74. doi: 10.1016/s0006-291x(03)00358-9.
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• [8] Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging.Biomaterials. 2018 Nov;183:67-76. doi: 10.1016/j.biomaterials.2018.08.039. Epub 2018 Aug 22.
• [9] Antiproliferative and Proapoptotic Effects of a Protein Component Purified from Aspongopus chinensis Dallas on Cancer Cells In Vitro and In Vivo.Evid Based Complement Alternat Med. 2019 Jan 3;2019:8934794. doi: 10.1155/2019/8934794. eCollection 2019.
• [10] In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides.ACS Nano. 2017 Oct 24;11(10):9825-9835. doi: 10.1021/acsnano.7b03150. Epub 2017 Sep 18.
• [11] Autophagy Promotes Survival of CHP-212 Neuroblastoma Cells Treated With Casiopenas.Anticancer Res. 2019 Jul;39(7):3687-3695. doi: 10.21873/anticanres.13517.
• [12] SNPs in axon guidance pathway genes and susceptibility for Parkinson's disease in the Korean population.J Hum Genet. 2011 Feb;56(2):125-9. doi: 10.1038/jhg.2010.130. Epub 2010 Nov 18.
• [13] 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.
• [14] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [19] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.