Details of Drug Off-Target (DOT)

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

• DOT Name: Regulator of G-protein signaling 19 (RGS19)
• Synonyms: RGS19; G-alpha-interacting protein; GAIP
• Gene Name: RGS19
• Related Disease:
  Colon cancer
  Colon carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Pancreatic adenocarcinoma
• UniProt ID: RGS19_HUMAN
• PDB ID: 1CMZ
• Pfam ID: PF00615
• Sequence:
  MPTPHEAEKQITGPEEADRPPSMSSHDTASPAAPSRNPCCLCWCCCCSCSWNQERRRAWQ
  ASRESKLQPLPSCEVCATPSPEEVQSWAQSFDKLMHSPAGRSVFRAFLRTEYSEENMLFW
  LACEELKAEANQHVVDEKARLIYEDYVSILSPKEVSLDSRVREGINKKMQEPSAHTFDDA
  QLQIYTLMHRDSYPRFLSSPTYRALLLQGPSQSSSEA
• 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-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a >> G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein.
• Tissue Specificity: Highest expression in lung. Placenta, liver and heart also express high levels of GAIP.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[3]

2 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 Regulator of G-protein signaling 19 (RGS19).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Regulator of G-protein signaling 19 (RGS19).	[13]

11 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 Regulator of G-protein signaling 19 (RGS19).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Regulator of G-protein signaling 19 (RGS19).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Regulator of G-protein signaling 19 (RGS19).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Regulator of G-protein signaling 19 (RGS19).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Regulator of G-protein signaling 19 (RGS19).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Regulator of G-protein signaling 19 (RGS19).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Regulator of G-protein signaling 19 (RGS19).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Regulator of G-protein signaling 19 (RGS19).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Regulator of G-protein signaling 19 (RGS19).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Regulator of G-protein signaling 19 (RGS19).	[15]
Choline	DM5D9YK	Investigative	Choline affects the expression of Regulator of G-protein signaling 19 (RGS19).	[16]

References

• [1] Subcellular localization of the Galphai3 protein and G alpha interacting protein, two proteins involved in the control of macroautophagy in human colon cancer HT-29 cells.Biochem J. 1999 Jan 15;337 ( Pt 2)(Pt 2):289-95.
• [2] Regulator of G protein signaling 19 suppresses Ras-induced neoplastic transformation and tumorigenesis.Cancer Lett. 2013 Oct 1;339(1):33-41. doi: 10.1016/j.canlet.2013.07.025. Epub 2013 Jul 30.
• [3] Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma.Cancer Res. 2006 Nov 1;66(21):10264-8. doi: 10.1158/0008-5472.CAN-06-2321.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.