Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-4 receptor subunit alpha (IL4R)
• Synonyms: IL-4 receptor subunit alpha; IL-4R subunit alpha; IL-4R-alpha; IL-4RA; CD antigen CD124
• Gene Name: IL4R
• Related Disease: IgE responsiveness, atopic
• UniProt ID: IL4RA_HUMAN
• PDB ID: 1IAR; 1IRS; 3BPL; 3BPN; 3BPO; 5E4E; 6OEL; 6WGL
• Pfam ID: PF09238
• Sequence:
  MGWLCSGLLFPVSCLVLLQVASSGNMKVLQEPTCVSDYMSISTCEWKMNGPTNCSTELRL
  LYQLVFLLSEAHTCIPENNGGAGCVCHLLMDDVVSADNYTLDLWAGQQLLWKGSFKPSEH
  VKPRAPGNLTVHTNVSDTLLLTWSNPYPPDNYLYNHLTYAVNIWSENDPADFRIYNVTYL
  EPSLRIAASTLKSGISYRARVRAWAQCYNTTWSEWSPSTKWHNSYREPFEQHLLLGVSVS
  CIVILAVCLLCYVSITKIKKEWWDQIPNPARSRLVAIIIQDAQGSQWEKRSRGQEPAKCP
  HWKNCLTKLLPCFLEHNMKRDEDPHKAAKEMPFQGSGKSAWCPVEISKTVLWPESISVVR
  CVELFEAPVECEEEEEVEEEKGSFCASPESSRDDFQEGREGIVARLTESLFLDLLGEENG
  GFCQQDMGESCLLPPSGSTSAHMPWDEFPSAGPKEAPPWGKEQPLHLEPSPPASPTQSPD
  NLTCTETPLVIAGNPAYRSFSNSLSQSPCPRELGPDPLLARHLEEVEPEMPCVPQLSEPT
  TVPQPEPETWEQILRRNVLQHGAAAAPVSAPTSGYQEFVHAVEQGGTQASAVVGLGPPGE
  AGYKAFSSLLASSAVSPEKCGFGASSGEEGYKPFQDLIPGCPGDPAPVPVPLFTFGLDRE
  PPRSPQSSHLPSSSPEHLGLEPGEKVEDMPKPPLPQEQATDPLVDSLGSGIVYSALTCHL
  CGHLKQCHGQEDGGQTPVMASPCCGCCCGDRSSPPTTPLRAPDPSPGGVPLEASLCPASL
  APSGISEKSKSSSSFHPAPGNAQSSSQTPKIVNFVSVGPTYMRVS
• Function: Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2; Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.
• Tissue Specificity: Isoform 1 and isoform 2 are highly expressed in activated T-cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Pathways in cancer (hsa05200)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
IgE responsiveness, atopic	DISAE27V	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Interleukin-4 receptor subunit alpha (IL4R).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interleukin-4 receptor subunit alpha (IL4R).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Interleukin-4 receptor subunit alpha (IL4R).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interleukin-4 receptor subunit alpha (IL4R).	[18]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[21]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[22]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[23]
Budesonide	DMJIBAW	Approved	Budesonide decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[24]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[26]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[19]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Interleukin-4 receptor subunit alpha (IL4R).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[32]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[33]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interleukin-4 receptor subunit alpha (IL4R).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Interleukin-4 receptor subunit alpha (IL4R).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-4 receptor subunit alpha (IL4R).	[28]

References

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