Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-17 receptor E (IL17RE)
• Synonyms: IL-17 receptor E; IL-17RE
• Gene Name: IL17RE
• Related Disease:
  Anemia
  Malaria
  Autoimmune hepatitis
  Coeliac disease
  Hepatitis
  Hepatitis A virus infection
  Pneumonia
  Pneumonitis
  Autoimmune disease
  Nephropathy
• UniProt ID: I17RE_HUMAN
• Pfam ID: PF15037 ; PF08357
• Sequence:
  MGSSRLAALLLPLLLIVIDLSDSAGIGFRHLPHWNTRCPLASHTDDSFTGSSAYIPCRTW
  WALFSTKPWCVRVWHCSRCLCQHLLSGGSGLQRGLFHLLVQKSKKSSTFKFYRRHKMPAP
  AQRKLLPRRHLSEKSHHISIPSPDISHKGLRSKRTQPSDPETWESLPRLDSQRHGGPEFS
  FDLLPEARAIRVTISSGPEVSVRLCHQWALECEELSSPYDVQKIVSGGHTVELPYEFLLP
  CLCIEASYLQEDTVRRKKCPFQSWPEAYGSDFWKSVHFTDYSQHTQMVMALTLRCPLKLE
  AALCQRHDWHTLCKDLPNATARESDGWYVLEKVDLHPQLCFKFSFGNSSHVECPHQTGSL
  TSWNVSMDTQAQQLILHFSSRMHATFSAAWSLPGLGQDTLVPPVYTVSQARGSSPVSLDL
  IIPFLRPGCCVLVWRSDVQFAWKHLLCPDVSYRHLGLLILALLALLTLLGVVLALTCRRP
  QSGPGPARPVLLLHAADSEAQRRLVGALAELLRAALGGGRDVIVDLWEGRHVARVGPLPW
  LWAARTRVAREQGTVLLLWSGADLRPVSGPDPRAAPLLALLHAAPRPLLLLAYFSRLCAK
  GDIPPPLRALPRYRLLRDLPRLLRALDARPFAEATSWGRLGARQRRQSRLELCSRLEREA
  ARLADLG
• Function: Specific functional receptor for IL17C. May be signaling through the NF-kappa-B and MAPK pathways. May require TRAF3IP2 /ACT1 for signaling. May be a crucial regulator in innate immunity to bacterial pathogens. Isoform 2 and isoform 4 may be either cytoplasmic inactive or dominant active forms. Isoform 3 and isoform 5 may act as soluble decoy receptors.
• Tissue Specificity: Predominantly expressed in mucosal tissues with high levels in keratinocytes and colon epithelial cells. Very low expression in dermal fibroblasts. Expressed in various tumor cell lines.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  IL-17 sig.ling pathway (hsa04657)
• Reactome Pathway: Interleukin-17 signaling (R-HSA-448424)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia	DISTVL0C	Definitive	Genetic Variation	[1]
Malaria	DISQ9Y50	Definitive	Genetic Variation	[1]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[2]
Coeliac disease	DISIY60C	Strong	Altered Expression	[3]
Hepatitis	DISXXX35	Strong	Biomarker	[2]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[2]
Pneumonia	DIS8EF3M	Strong	Biomarker	[4]
Pneumonitis	DIS88E0K	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Limited	Biomarker	[5]
Nephropathy	DISXWP4P	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-17 receptor E (IL17RE).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interleukin-17 receptor E (IL17RE).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interleukin-17 receptor E (IL17RE).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Interleukin-17 receptor E (IL17RE).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interleukin-17 receptor E (IL17RE).	[10]

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 Interleukin-17 receptor E (IL17RE).	[11]

References

• [1] Association of cytokine and Toll-like receptor gene polymorphisms with severe malaria in three regions of Cameroon.PLoS One. 2013 Nov 27;8(11):e81071. doi: 10.1371/journal.pone.0081071. eCollection 2013.
• [2] IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis.J Immunol. 2017 Jan 15;198(2):669-680. doi: 10.4049/jimmunol.1600977. Epub 2016 Dec 12.
• [3] Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease.Scand J Gastroenterol. 2014 Feb;49(2):145-56. doi: 10.3109/00365521.2013.863966. Epub 2013 Dec 10.
• [4] Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia.Infect Immun. 2019 Oct 18;87(11):e00329-19. doi: 10.1128/IAI.00329-19. Print 2019 Nov.
• [5] IL-17C/IL-17 Receptor E Signaling in CD4(+) T Cells Promotes T(H)17 Cell-Driven Glomerular Inflammation.J Am Soc Nephrol. 2018 Apr;29(4):1210-1222. doi: 10.1681/ASN.2017090949. Epub 2018 Feb 26.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.