Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7T1EY)

• DOT Name: Interleukin-20 (IL20)
• Synonyms: IL-20; Cytokine Zcyto10
• Gene Name: IL20
• UniProt ID: IL20_HUMAN
• PDB ID: 4DOH
• Pfam ID: PF00726
• Sequence:
  MKASSLAFSLLSAAFYLLWTPSTGLKTLNLGSCVIATNLQEIRNGFSEIRGSVQAKDGNI
  DIRILRRTESLQDTKPANRCCLLRHLLRLYLDRVFKNYQTPDHYTLRKISSLANSFLTIK
  KDLRLCHAHMTCHCGEEAMKKYSQILSHFEKLEPQAAVVKALGELDILLQWMEETE
• Function: Pro-inflammatory and angiogenic cytokine mainly secreted by monocytes and skin keratinocytes that plays crucial roles in immune responses, regulation of inflammatory responses, hemopoiesis, as well as epidermal cell and keratinocyte differentiation. Enhances tissue remodeling and wound-healing activities and restores the homeostasis of epithelial layers during infection and inflammatory responses to maintain tissue integrity. Affects multiple actin-mediated functions in activated neutrophils leading to inhibition of phagocytosis, granule exocytosis, and migration. Exert its effects via the type I IL-20 receptor complex consisting of IL20RA and IL20RB. Alternatively, can mediate its activity through a second receptor complex called type II IL-20 receptor complex composed of IL22RA1 and IL20RB. Acts as an arteriogenic and vascular remodeling factory by activating a range of signaling processes including phosphorylations of JAK2 and STAT5 as well as activation of the serine and threonine kinases AKT and ERK1/2. Alternatively, can activate STAT3 phosphorylation and transcriptional activity in a JAK2, ERK1/2 and p38 MAPK-dependent manner in keratinocytes.
• Tissue Specificity: Expressed in most tissues and five major cell types: epithelial cells (primarily skin, buccal mucosa, tongue, nasal mucosa, lung, ureter, breast, prostate, fallopian tube, and adrenal gland), myoepithelial cells (mainly prostate), endothelial cells (mainly in small vessels or capillaries), macrophages, and skeletal muscle. Isoform 2 was detected in the lung tissue only.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-20 (IL20).	[1]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interleukin-20 (IL20).	[3]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Interleukin-20 (IL20).	[4]
PATULIN	DM0RV9C	Investigative	PATULIN increases the expression of Interleukin-20 (IL20).	[5]

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 decreases the methylation of Interleukin-20 (IL20).	[2]

References

• [1] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [2] 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.
• [3] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [4] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [5] Patulin induces pyroptosis through the autophagic-inflammasomal pathway in liver. Food Chem Toxicol. 2021 Jan;147:111867. doi: 10.1016/j.fct.2020.111867. Epub 2020 Nov 17.