Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCUB1EV)

• DOT Name: Interleukin-18 receptor accessory protein (IL18RAP)
• Synonyms: IL-18 receptor accessory protein; IL-18RAcP; EC 3.2.2.6; Accessory protein-like; AcPL; CD218 antigen-like family member B; CDw218b; IL-1R accessory protein-like; IL-1RAcPL; Interleukin-1 receptor 7; IL-1R-7; IL-1R7; Interleukin-18 receptor accessory protein-like; Interleukin-18 receptor beta; IL-18R-beta; IL-18Rbeta; CD antigen CD218b
• Gene Name: IL18RAP
• UniProt ID: I18RA_HUMAN
• PDB ID: 3WO4; 6KN9; 7FCH
• EC Number: 3.2.2.6
• Pfam ID: PF18452 ; PF01582
• Sequence:
  MLCLGWIFLWLVAGERIKGFNISGCSTKKLLWTYSTRSEEEFVLFCDLPEPQKSHFCHRN
  RLSPKQVPEHLPFMGSNDLSDVQWYQQPSNGDPLEDIRKSYPHIIQDKCTLHFLTPGVNN
  SGSYICRPKMIKSPYDVACCVKMILEVKPQTNASCEYSASHKQDLLLGSTGSISCPSLSC
  QSDAQSPAVTWYKNGKLLSVERSNRIVVDEVYDYHQGTYVCDYTQSDTVSSWTVRAVVQV
  RTIVGDTKLKPDILDPVEDTLEVELGKPLTISCKARFGFERVFNPVIKWYIKDSDLEWEV
  SVPEAKSIKSTLKDEIIERNIILEKVTQRDLRRKFVCFVQNSIGNTTQSVQLKEKRGVVL
  LYILLGTIGTLVAVLAASALLYRHWIEIVLLYRTYQSKDQTLGDKKDFDAFVSYAKWSSF
  PSEATSSLSEEHLALSLFPDVLENKYGYSLCLLERDVAPGGVYAEDIVSIIKRSRRGIFI
  LSPNYVNGPSIFELQAAVNLALDDQTLKLILIKFCYFQEPESLPHLVKKALRVLPTVTWR
  GLKSVPPNSRFWAKMRYHMPVKNSQGFTWNQLRITSRIFQWKGLSRTETTGRSSQPKEW
• Function: Within the IL18 receptor complex, does not mediate IL18-binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation. May play a role in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells (Probable).
• Tissue Specificity: Detected in adrenal gland, bone marrow, brain, fetal brain, fetal liver, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, prostate, salivary gland, skeletal muscle, spinal cord, testis, thymus, thyroid, trachea and uterus . Strongly expressed in peripheral blood leukocytes and spleen and, to a lesser extent, in colon . Specifically coexpressed with IL18R1 in T-helper 1 (Th1)cells .
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway: Interleukin-18 signaling (R-HSA-9012546)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-18 receptor accessory protein (IL18RAP).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Interleukin-18 receptor accessory protein (IL18RAP).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Interleukin-18 receptor accessory protein (IL18RAP).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-18 receptor accessory protein (IL18RAP).	[4]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interleukin-18 receptor accessory protein (IL18RAP).	[5]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [3] Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [5] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.