Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPAMQ18)

• DOT Name: Regulator of G-protein signaling 13 (RGS13)
• Synonyms: RGS13
• Gene Name: RGS13
• Related Disease:
  Pediatric lymphoma
  Mantle cell lymphoma
  Non-insulin dependent diabetes
  Adult lymphoma
  Burkitt lymphoma
  Lymphoma
• UniProt ID: RGS13_HUMAN
• Pfam ID: PF00615
• Sequence:
  MSRRNCWICKMCRDESKRPPSNLTLEEVLQWAQSFENLMATKYGPVVYAAYLKMEHSDEN
  IQFWMACETYKKIASRWSRISRAKKLYKIYIQPQSPREINIDSSTRETIIRNIQEPTETC
  FEEAQKIVYMHMERDSYPRFLKSEMYQKLLKTMQSNNSF
• 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 both G(i)-alpha and G(q)-alpha.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pediatric lymphoma	DIS51BK2	Definitive	Altered Expression	[1]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Adult lymphoma	DISK8IZR	Disputed	Altered Expression	[1]
Burkitt lymphoma	DIS9D5XU	Disputed	Altered Expression	[1]
Lymphoma	DISN6V4S	Disputed	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Regulator of G-protein signaling 13 (RGS13).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Regulator of G-protein signaling 13 (RGS13).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Regulator of G-protein signaling 13 (RGS13).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Regulator of G-protein signaling 13 (RGS13).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Regulator of G-protein signaling 13 (RGS13).	[14]

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 affects the methylation of Regulator of G-protein signaling 13 (RGS13).	[13]

References

• [1] RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization.J Leukoc Biol. 2006 Jun;79(6):1357-68. doi: 10.1189/jlb.1105693. Epub 2006 Mar 24.
• [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] A genome-wide association study implicates that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity.Ophthalmic Genet. 2019 Jun;40(3):252-258. doi: 10.1080/13816810.2019.1633549. Epub 2019 Jul 2.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [7] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.