Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2MO458)

• DOT Name: G-protein-signaling modulator 3 (GPSM3)
• Synonyms: Activator of G-protein signaling 4; G18.1b; Protein G18
• Gene Name: GPSM3
• Related Disease:
  Hepatitis B virus infection
  Leukopenia
  Myasthenia gravis
  Promyelocytic leukaemia
  Type-1 diabetes
  Arthritis
  Rheumatoid arthritis
  Systemic lupus erythematosus
• UniProt ID: GPSM3_HUMAN
• Pfam ID: PF02188
• Sequence:
  MEAERPQEEEDGEQGPPQDEEGWPPPNSTTRPWRSAPPSPPPPGTRHTALGPRSASLLSL
  QTELLLDLVAEAQSRRLEEQRATFYTPQNPSSLAPAPLRPLEDREQLYSTILSHQCQRME
  AQRSEPPLPPGGQELLELLLRVQGGGRMEEQRSRPPTHTC
• Function: Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins.
• Tissue Specificity: Expressed in heart, placenta, lung and liver.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway: G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[1]
Leukopenia	DISJMBMM	Strong	Biomarker	[2]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[3]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[4]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[5]
Arthritis	DIST1YEL	Limited	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[6]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of G-protein-signaling modulator 3 (GPSM3).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of G-protein-signaling modulator 3 (GPSM3).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of G-protein-signaling modulator 3 (GPSM3).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of G-protein-signaling modulator 3 (GPSM3).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of G-protein-signaling modulator 3 (GPSM3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of G-protein-signaling modulator 3 (GPSM3).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of G-protein-signaling modulator 3 (GPSM3).	[15]

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 G-protein-signaling modulator 3 (GPSM3).	[14]

References

• [1] A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population.Hum Mol Genet. 2011 Oct 1;20(19):3884-92. doi: 10.1093/hmg/ddr301. Epub 2011 Jul 12.
• [2] Regulation of Chemokine Signal Integration by Activator of G-Protein Signaling 4 (AGS4).J Pharmacol Exp Ther. 2017 Mar;360(3):424-433. doi: 10.1124/jpet.116.238436. Epub 2017 Jan 6.
• [3] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [4] Reduction of GPSM3 expression akin to the arthritis-protective SNP rs204989 differentially affects migration in a neutrophil model.Genes Immun. 2016 Sep;17(6):321-7. doi: 10.1038/gene.2016.26. Epub 2016 Jun 16.
• [5] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [6] Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance.Genes Immun. 2016 Mar;17(2):139-47. doi: 10.1038/gene.2016.3. Epub 2016 Jan 28.
• [7] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [8] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [9] 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.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] 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.
• [15] 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.