Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPC2G0X)

• DOT Name: Interleukin-13 receptor subunit alpha-2 (IL13RA2)
• Synonyms: IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; Interleukin-13-binding protein; CD antigen CD213a2
• Gene Name: IL13RA2
• UniProt ID: I13R2_HUMAN
• PDB ID: 3LB6
• Pfam ID: PF09240
• Sequence:
  MAFVCLAIGCLYTFLISTTFGCTSSSDTEIKVNPPQDFEIVDPGYLGYLYLQWQPPLSLD
  HFKECTVEYELKYRNIGSETWKTIITKNLHYKDGFDLNKGIEAKIHTLLPWQCTNGSEVQ
  SSWAETTYWISPQGIPETKVQDMDCVYYNWQYLLCSWKPGIGVLLDTNYNLFYWYEGLDH
  ALQCVDYIKADGQNIGCRFPYLEASDYKDFYICVNGSSENKPIRSSYFTFQLQNIVKPLP
  PVYLTFTRESSCEIKLKWSIPLGPIPARCFDYEIEIREDDTTLVTATVENETYTLKTTNE
  TRQLCFVVRSKVNIYCSDDGIWSEWSDKQCWEGEDLSKKTLLRFWLPFGFILILVIFVTG
  LLLRKPNTYPKMIPEFFCDT
• Function: Binds as a monomer with high affinity to interleukin-13 (IL13), but not to interleukin-4 (IL4).
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Interleukin-13 receptor subunit alpha-2 (IL13RA2) affects the response to substance of Paclitaxel.	[17]
Mitoxantrone	DMM39BF	Approved	Interleukin-13 receptor subunit alpha-2 (IL13RA2) affects the response to substance of Mitoxantrone.	[17]
Vinblastine	DM5TVS3	Approved	Interleukin-13 receptor subunit alpha-2 (IL13RA2) affects the response to substance of Vinblastine.	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[1]

17 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 Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[10]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[11]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[12]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[13]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[15]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[9]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[16]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Interleukin-13 receptor subunit alpha-2 (IL13RA2).	[9]

References

• [1] 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.
• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [5] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] 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.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands. Endocrinology. 2010 Sep;151(9):4515-26. doi: 10.1210/en.2009-1398. Epub 2010 Jul 21.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [12] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [13] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [14] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [16] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.