Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDLV8H8)

• DOT Name: Interleukin-12 receptor subunit beta-2 (IL12RB2)
• Synonyms: IL-12 receptor subunit beta-2; IL-12R subunit beta-2; IL-12R-beta-2; IL-12RB2
• Gene Name: IL12RB2
• UniProt ID: I12R2_HUMAN
• Pfam ID: PF00041 ; PF06328
• Sequence:
  MAHTFRGCSLAFMFIITWLLIKAKIDACKRGDVTVKPSHVILLGSTVNITCSLKPRQGCF
  HYSRRNKLILYKFDRRINFHHGHSLNSQVTGLPLGTTLFVCKLACINSDEIQICGAEIFV
  GVAPEQPQNLSCIQKGEQGTVACTWERGRDTHLYTEYTLQLSGPKNLTWQKQCKDIYCDY
  LDFGINLTPESPESNFTAKVTAVNSLGSSSSLPSTFTFLDIVRPLPPWDIRIKFQKASVS
  RCTLYWRDEGLVLLNRLRYRPSNSRLWNMVNVTKAKGRHDLLDLKPFTEYEFQISSKLHL
  YKGSWSDWSESLRAQTPEEEPTGMLDVWYMKRHIDYSRQQISLFWKNLSVSEARGKILHY
  QVTLQELTGGKAMTQNITGHTSWTTVIPRTGNWAVAVSAANSKGSSLPTRINIMNLCEAG
  LLAPRQVSANSEGMDNILVTWQPPRKDPSAVQEYVVEWRELHPGGDTQVPLNWLRSRPYN
  VSALISENIKSYICYEIRVYALSGDQGGCSSILGNSKHKAPLSGPHINAITEEKGSILIS
  WNSIPVQEQMGCLLHYRIYWKERDSNSQPQLCEIPYRVSQNSHPINSLQPRVTYVLWMTA
  LTAAGESSHGNEREFCLQGKANWMAFVAPSICIAIIMVGIFSTHYFQQKVFVLLAALRPQ
  WCSREIPDPANSTCAKKYPIAEEKTQLPLDRLLIDWPTPEDPEPLVISEVLHQVTPVFRH
  PPCSNWPQREKGIQGHQASEKDMMHSASSPPPPRALQAESRQLVDLYKVLESRGSDPKPE
  NPACPWTVLPAGDLPTHDGYLPSNIDDLPSHEAPLADSLEELEPQHISLSVFPSSSLHPL
  TFSCGDKLTLDQLKMRCDSLML
• Function: Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production.
• Tissue Specificity: Isoform 2 is expressed at similar levels in both naive and activated T-cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Th1 and Th2 cell differentiation (hsa04658)
  Pathways in cancer (hsa05200)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway:
  Interleukin-12 signaling (R-HSA-9020591)
  Interleukin-35 Signalling (R-HSA-8984722)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[6]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[7]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[6]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[8]

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 affects the methylation of Interleukin-12 receptor subunit beta-2 (IL12RB2).	[9]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Silencer activity of NFATc2 in the interleukin-12 receptor beta 2 proximal promoter in human T helper cells. J Biol Chem. 2001 Sep 14;276(37):34509-16. doi: 10.1074/jbc.M102536200. Epub 2001 Jul 3.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [5] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [6] Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol. 1998 Sep 15;161(6):2723-30.
• [7] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [8] Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes eosinophil apoptosis. J Immunol. 2001 Jul 15;167(2):1039-46. doi: 10.4049/jimmunol.167.2.1039.
• [9] 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.