General Information of Drug Off-Target (DOT) (ID: OTW31FU9)

DOT Name Interleukin-22 (IL22)
Synonyms IL-22; Cytokine Zcyto18; IL-10-related T-cell-derived-inducible factor; IL-TIF
Gene Name IL22
UniProt ID
IL22_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1M4R; 1YKB; 3DGC; 3DLQ; 3G9V; 3Q1S
Pfam ID
PF14565
Sequence
MAALQKSVSSFLMGTLATSCLLLLALLVQGGAAAPISSHCRLDKSNFQQPYITNRTFMLA
KEASLADNNTDVRLIGEKLFHGVSMSERCYLMKQVLNFTLEEVLFPQSDRFQPYMQEVVP
FLARLSNRLSTCHIEGDDLHIQRNVQKLKDTVKKLGESGEIKAIGELDLLFMSLRNACI
Function
Cytokine that plays a critical role in modulating tissue responses during inflammation. Plays an essential role in the regeneration of epithelial cells to maintain barrier function after injury and for the prevention of further tissue damage. Unlike most of the cytokines, has no effect on immune cells. Signals through a heterodimeric receptor composed of two subunits, the specific receptor IL22RA1 which is present on non-immune cells in many organs and the shared subunit IL10RB. Ligation of IL22RA1 with IL22 induces activation of the tyrosine kinases JAK1 and TYK2, which in turn activates STAT3. In turn, promotes cell survival and proliferation through STAT3, ERK1/2 and PI3K/AKT pathways. Promotes phosphorylation of GSK3B at 'Ser-9' and CTTN. Promotes epithelial cell spreading.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
JAK-STAT sig.ling pathway (hsa04630 )
Th17 cell differentiation (hsa04659 )
Inflammatory bowel disease (hsa05321 )
Reactome Pathway
Interleukin-20 family signaling (R-HSA-8854691 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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-22 (IL22). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Interleukin-22 (IL22). [5]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Interleukin-22 (IL22). [6]
------------------------------------------------------------------------------------
2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the secretion of Interleukin-22 (IL22). [2]
Simvastatin DM30SGU Approved Simvastatin decreases the secretion of Interleukin-22 (IL22). [3]
------------------------------------------------------------------------------------
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dinoprostone DMTYOPD Approved Dinoprostone decreases the expression of Interleukin-22 (IL22). [4]
SGC-CBP30 DMTLRGZ Investigative SGC-CBP30 decreases the expression of Interleukin-22 (IL22). [7]
------------------------------------------------------------------------------------

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 Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
3 Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell differentiation in CD4+ T cells derived from patients with multiple sclerosis. J Immunol. 2011 Sep 15;187(6):3431-7. doi: 10.4049/jimmunol.1100580. Epub 2011 Aug 19.
4 Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009 Mar 16;206(3):535-48. doi: 10.1084/jem.20082293. Epub 2009 Mar 9.
5 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.
6 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.
7 CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10768-73. doi: 10.1073/pnas.1501956112. Epub 2015 Aug 10.