Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-22 receptor subunit alpha-2 (IL22RA2)
• Synonyms: IL-22 receptor subunit alpha-2; IL-22R-alpha-2; IL-22RA2; Cytokine receptor class-II member 10; Cytokine receptor family 2 member 10; CRF2-10; Cytokine receptor family type 2, soluble 1; CRF2-S1; Interleukin-22-binding protein; IL-22BP; IL22BP; ZcytoR16
• Gene Name: IL22RA2
• Related Disease:
  Autoimmune disease
  Colon cancer
  Colon carcinoma
  Dermatitis
  Glioma
  Inflammation
  Multiple sclerosis
  Psoriasis
  Skin disease
  Vitiligo
  Influenza
  Lupus nephritis
  Pneumonia
  Pneumonitis
  Systemic lupus erythematosus
  Colitis
  Inflammatory bowel disease
  Periodontitis
  Streptococcal pneumonia
• UniProt ID: I22R2_HUMAN
• PDB ID: 3G9V
• Pfam ID: PF09294 ; PF01108
• Sequence:
  MMPKHCFLGFLISFFLTGVAGTQSTHESLKPQRVQFQSRNFHNILQWQPGRALTGNSSVY
  FVQYKIMFSCSMKSSHQKPSGCWQHISCNFPGCRTLAKYGQRQWKNKEDCWGTQELSCDL
  TSETSDIQEPYYGRVRAASAGSYSEWSMTPRFTPWWETKIDPPVMNITQVNGSLLVILHA
  PNLPYRYQKEKNVSIEDYYELLYRVFIINNSLEKEQKVYEGAHRAVEIEALTPHSSYCVV
  AEIYQPMLDRRSQRSEERCVEIP
• Function: Isoform 2 is a receptor for IL22. Binds to IL22, prevents interaction with the functional IL-22R complex and blocks the activity of IL22 (in vitro). May play an important role as an IL22 antagonist in the regulation of inflammatory responses.; Isoform 1 may play a role in establishing and maintaining successful pregnancy.
• Tissue Specificity: Expressed in placenta, spleen, breast, skin and lung. Also detected in intestinal tract, testis, brain, heart and thymus. No expression found in prostate, bladder, kidney, ovary, muscle, bone marrow, liver and uterus. Isoform 1 is expressed only in placenta. Isoform 2 is expressed in placenta and breast and at lower level in spleen, skin, thymus and stomach.
• KEGG Pathway: JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Dermatitis	DISY5SZC	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Inflammation	DISJUQ5T	Strong	Altered Expression	[1]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[5]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Skin disease	DISDW8R6	Strong	Altered Expression	[1]
Vitiligo	DISR05SL	Strong	Biomarker	[6]
Influenza	DIS3PNU3	moderate	Biomarker	[7]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[8]
Pneumonia	DIS8EF3M	moderate	Biomarker	[7]
Pneumonitis	DIS88E0K	moderate	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	moderate	Altered Expression	[8]
Colitis	DISAF7DD	Limited	Altered Expression	[9]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[10]
Periodontitis	DISI9JOI	Limited	Biomarker	[11]
Streptococcal pneumonia	DIS2EKMJ	Limited	Biomarker	[12]

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 increases the methylation of Interleukin-22 receptor subunit alpha-2 (IL22RA2).	[13]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of Interleukin-22 receptor subunit alpha-2 (IL22RA2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Interleukin-22 receptor subunit alpha-2 (IL22RA2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Interleukin-22 receptor subunit alpha-2 (IL22RA2).	[15]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interleukin-22 receptor subunit alpha-2 (IL22RA2).	[14]

References

• [1] Regulation of IL-22BP in psoriasis.Sci Rep. 2018 Mar 23;8(1):5085. doi: 10.1038/s41598-018-23510-3.
• [2] Delivery of a Modified mRNA Encoding IL-22 Binding Protein (IL-22BP) for Colon Cancer Gene Therapy.J Biomed Nanotechnol. 2018 Jul 1;14(7):1239-1251. doi: 10.1166/jbn.2018.2577.
• [3] Pivotal Role of IL-22 Binding Protein in the Epithelial Autoregulation of Interleukin-22 Signaling in the Control of Skin Inflammation.Front Immunol. 2018 Jun 21;9:1418. doi: 10.3389/fimmu.2018.01418. eCollection 2018.
• [4] The inflammatory cytokine IL-22 promotes murine gliomas via proliferation.Exp Ther Med. 2017 Mar;13(3):1087-1092. doi: 10.3892/etm.2017.4059. Epub 2017 Jan 18.
• [5] IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis.J Immunol. 2019 Aug 15;203(4):888-898. doi: 10.4049/jimmunol.1900400. Epub 2019 Jul 10.
• [6] The mRNA expression profile of cytokines connected to the regulation of melanocyte functioning in vitiligo skin biopsy samples and peripheral blood mononuclear cells.Hum Immunol. 2012 Apr;73(4):393-8. doi: 10.1016/j.humimm.2012.01.011. Epub 2012 Jan 31.
• [7] Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection.Mucosal Immunol. 2020 Jan;13(1):64-74. doi: 10.1038/s41385-019-0206-9. Epub 2019 Oct 9.
• [8] Urinary interleukin 22 binding protein as a marker of lupus nephritis in Egyptian children with juvenile systemic lupus erythematosus.Clin Rheumatol. 2018 Feb;37(2):451-458. doi: 10.1007/s10067-017-3812-5. Epub 2017 Sep 9.
• [9] Modified apple polysaccharide prevents colitis through modulating IL-22 and IL-22BP expression.Int J Biol Macromol. 2017 Oct;103:1217-1223. doi: 10.1016/j.ijbiomac.2017.05.172. Epub 2017 Jun 1.
• [10] Expression Profiling of Inflammatory and Immunological Genes in Collagenous Colitis.J Crohns Colitis. 2019 May 27;13(6):764-771. doi: 10.1093/ecco-jcc/jjy224.
• [11] Temporal expression of interleukin-22, interleukin-22 receptor 1 and interleukin-22-binding protein during experimental periodontitis in rats.J Periodontal Res. 2018 Apr;53(2):250-257. doi: 10.1111/jre.12512. Epub 2017 Oct 28.
• [12] Interleukin-22 (IL-22) Binding Protein Constrains IL-22 Activity, Host Defense, and Oxidative Phosphorylation Genes during Pneumococcal Pneumonia.Infect Immun. 2019 Oct 18;87(11):e00550-19. doi: 10.1128/IAI.00550-19. Print 2019 Nov.
• [13] 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.
• [14] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.