Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTETA815)

• DOT Name: GTP-binding protein Rhes (RASD2)
• Synonyms: Ras homolog enriched in striatum; Tumor endothelial marker 2
• Gene Name: RASD2
• Related Disease:
  Huntington disease
  Tuberous sclerosis 1
  Lung cancer
  Lung carcinoma
  Colorectal carcinoma
  Schizophrenia
• UniProt ID: RHES_HUMAN
• Pfam ID: PF00071
• Sequence:
  MMKTLSSGNCTLSVPAKNSYRMVVLGASRVGKSSIVSRFLNGRFEDQYTPTIEDFHRKVY
  NIRGDMYQLDILDTSGNHPFPAMRRLSILTGDVFILVFSLDNRESFDEVKRLQKQILEVK
  SCLKNKTKEAAELPMVICGNKNDHGELCRQVPTTEAELLVSGDENCAYFEVSAKKNTNVD
  EMFYVLFSMAKLPHEMSPALHRKISVQYGDAFHPRPFCMRRVKEMDAYGMVSPFARRPSV
  NSDLKYIKAKVLREGQARERDKCTIQ
• Function: GTPase signaling protein that binds to and hydrolyzes GTP. Regulates signaling pathways involving G-proteins-coupled receptor and heterotrimeric proteins such as GNB1, GNB2 and GNB3. May be involved in selected striatal competencies, mainly locomotor activity and motor coordination.
• Tissue Specificity: Pancreatic endocrine cells (islets of Langerhans).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Huntington disease	DISQPLA4	Strong	Biomarker	[1]
Tuberous sclerosis 1	DIS07GDN	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	moderate	Altered Expression	[3]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[4]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of GTP-binding protein Rhes (RASD2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GTP-binding protein Rhes (RASD2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of GTP-binding protein Rhes (RASD2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of GTP-binding protein Rhes (RASD2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of GTP-binding protein Rhes (RASD2).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of GTP-binding protein Rhes (RASD2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GTP-binding protein Rhes (RASD2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GTP-binding protein Rhes (RASD2).	[11]

References

• [1] Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy.Int J Mol Med. 2019 Dec;44(6):2223-2233. doi: 10.3892/ijmm.2019.4373. Epub 2019 Oct 15.
• [2] Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling.Front Mol Neurosci. 2017 Jun 28;10:201. doi: 10.3389/fnmol.2017.00201. eCollection 2017.
• [3] Study on lung cancer cells expressing VEGFR2 and the impact on the effect of RHES combined with radiotherapy in the treatment of brain metastases.Clin Lung Cancer. 2014 Mar;15(2):e23-9. doi: 10.1016/j.cllc.2013.11.012. Epub 2013 Nov 20.
• [4] Prognostic values of tumor endothelial markers in patients with colorectal cancer.World J Gastroenterol. 2005 Mar 7;11(9):1283-6. doi: 10.3748/wjg.v11.i9.1283.
• [5] Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.Neuropsychopharmacology. 2016 Feb;41(3):916-27. doi: 10.1038/npp.2015.228. Epub 2015 Jul 31.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] 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.
• [12] 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.