Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ6ZOCN)

• DOT Name: Regulator of G-protein signaling 18 (RGS18)
• Synonyms: RGS18
• Gene Name: RGS18
• Related Disease:
  Gastric cancer
  Stomach cancer
  Mantle cell lymphoma
• UniProt ID: RGS18_HUMAN
• PDB ID: 2DLV; 2JM5; 2OWI
• Pfam ID: PF00615
• Sequence:
  METTLLFFSQINMCESKEKTFFKLIHGSGKEETSKEAKIRAKEKRNRLSLLVQKPEFHED
  TRSSRSGHLAKETRVSPEEAVKWGESFDKLLSHRDGLEAFTRFLKTEFSEENIEFWIACE
  DFKKSKGPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVITNSITQPTLHSFDAAQSRV
  YQLMEQDSYTRFLKSDIYLDLMEGRPQRPTNLRRRSRSFTCNEFQDVQSDVAIWL
• Function: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i) alpha-1, G(i) alpha-2, G(i) alpha-3 and G(q) alpha.
• Tissue Specificity: Expressed in peripheral leukocytes, bone marrow, platelet, spleen and fetal liver.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[1]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Regulator of G-protein signaling 18 (RGS18).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Regulator of G-protein signaling 18 (RGS18).	[4]

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 decreases the methylation of Regulator of G-protein signaling 18 (RGS18).	[5]

References

• [1] Identification of plasma RGS18 and PPBP mRNAs as potential biomarkers for gastric cancer using transcriptome arrays.Oncol Lett. 2019 Jan;17(1):247-255. doi: 10.3892/ol.2018.9608. Epub 2018 Oct 23.
• [2] High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma.Leukemia. 2003 Sep;17(9):1880-90. doi: 10.1038/sj.leu.2403057.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 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.