Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMSLUG9)

• DOT Name: Interleukin-5 receptor subunit alpha (IL5RA)
• Synonyms: IL-5 receptor subunit alpha; IL-5R subunit alpha; IL-5R-alpha; IL-5RA; CDw125; CD antigen CD125
• Gene Name: IL5RA
• UniProt ID: IL5RA_HUMAN
• PDB ID: 1OBX; 1OBZ; 3QT2; 3VA2; 6H41
• Pfam ID: PF09240
• Sequence:
  MIIVAHVLLILLGATEILQADLLPDEKISLLPPVNFTIKVTGLAQVLLQWKPNPDQEQRN
  VNLEYQVKINAPKEDDYETRITESKCVTILHKGFSASVRTILQNDHSLLASSWASAELHA
  PPGSPGTSIVNLTCTTNTTEDNYSRLRSYQVSLHCTWLVGTDAPEDTQYFLYYRYGSWTE
  ECQEYSKDTLGRNIACWFPRTFILSKGRDWLAVLVNGSSKHSAIRPFDQLFALHAIDQIN
  PPLNVTAEIEGTRLSIQWEKPVSAFPIHCFDYEVKIHNTRNGYLQIEKLMTNAFISIIDD
  LSKYDVQVRAAVSSMCREAGLWSEWSQPIYVGNDEHKPLREWFVIVIMATICFILLILSL
  ICKICHLWIKLFPPIPAPKSNIKDLFVTTNYEKAGSSETEIEVICYIEKPGVETLEDSVF
• Function: Cell surface receptor that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Acts by forming an heterodimeric receptor with CSF2RB subunit and subsequently binding to interleukin-5. In unstimulated conditions, interacts constitutively with JAK2. Heterodimeric receptor activation leads to JAK2 stimulation and subsequent activation of the JAK-STAT pathway.
• Tissue Specificity: Expressed on eosinophils and basophils.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoproterenol	DMK7MEY	Approved	Interleukin-5 receptor subunit alpha (IL5RA) affects the response to substance of Isoproterenol.	[5]
Acetylcholine	DMDF79Z	Approved	Interleukin-5 receptor subunit alpha (IL5RA) increases the response to substance of Acetylcholine.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-5 receptor subunit alpha (IL5RA).	[1]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Interleukin-5 receptor subunit alpha (IL5RA).	[2]

2 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 Interleukin-5 receptor subunit alpha (IL5RA).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-5 receptor subunit alpha (IL5RA).	[4]

References

• [1] Changing the differentiation program of hematopoietic cells: retinoic acid-induced shift of eosinophil-committed cells to neutrophils. Blood. 1995 Nov 15;86(10):3737-44.
• [2] Interleukin-5 receptor alpha chain mRNA is down-regulated by transforming growth factor beta 1. Eur Cytokine Netw. 1994 Jan-Feb;5(1):35-42.
• [3] 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.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999 Sep;104(5):657-67. doi: 10.1172/JCI7137.
• [6] The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness. J Allergy Clin Immunol. 2002 Mar;109(3):404-9. doi: 10.1067/mai.2002.122459.