Details of Drug Off-Target (DOT)

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

• DOT Name: Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2)
• Synonyms: Lymphoid-restricted membrane protein; Protein Jaw1
• Gene Name: IRAG2
• UniProt ID: IRAG2_HUMAN
• PDB ID: 7Z8Y; 8B46; 8B5X
• Pfam ID: PF05781
• Sequence:
  MESTPFSGVANQIHTLCERPTYGEVKDGALDVKRQHKCPGPTSGPSPGTNLSGCIRMNDD
  PSMEENGVERVCPESLLQSREYSSLPLPRHTSSTDGTITSSDPGLEILNMASCDLDRNSL
  CKKEEDTRSASPTIEAQGTSPAHDNIAFQDSTSKDKTILNLEAKEEPETIEEHKKEHASG
  DSVVSPLPVTTVKSVNLRQSENTSANEKEVEAEFLRLSLGFKCDWFTLEKRVKLEERSRD
  LAEENLKKEITNCLKLLESLTPLCEDDNQAQEIIKKLEKSIKFLSQCAARVASRAEMLGA
  INQESRVSKAVEVMIQHVENLKRMYAKEHAELEELKQVLLQNERSFNPLEDDDDCQIKKR
  SASLNSKPSSLRRVTIASLPRNIGNAGMVAGMENNDRFSRRSSSWRILGSKQSEHRPSLP
  RFISTYSWADAEEEKCELKTKDDSEPSGEETVERTRKPSLSEKKNNPSKWDVSSVYDTIA
  SWATNLKSSIRKANKALWLSIAFIVLFAALMSFLTGQLFQKSVDAAPTQQEDSWTSLEHI
  LWPFTRLRHNGPPPV
• Function: Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner. May play a role in taste signal transduction via ITPR3. May play a role during fertilization in pronucleus congression and fusion. Plays a role in maintaining nuclear shape, maybe as a component of the LINC complex and through interaction with microtubules.
• Tissue Specificity: Expressed at high levels in pre B-cells, mature B-cells and pre T-cells. Expressed at low levels in mature T-cells and plasma B-cells. Expressed in germinal center B-cells, splenic marginal zone cells and B-cell lymphomas. Expressed in neuronal cells in the cerebral cortex, epithelial cells in tonsil, adrenal glands, zymogen-producing cells in the stomach and epithelial cells in seminal vesicles.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[2]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[3]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[4]
Rigosertib	DMOSTXF	Phase 3	Rigosertib affects the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[8]

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 Inositol 1,4,5-triphosphate receptor associated 2 (IRAG2).	[6]

References

• [1] 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.
• [2] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [3] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [4] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [5] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [6] 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.
• [7] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.