Details of Drug Off-Target (DOT)

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

• DOT Name: Paired immunoglobulin-like type 2 receptor beta (PILRB)
• Synonyms: Activating receptor PILR-beta; Cell surface receptor FDFACT
• Gene Name: PILRB
• UniProt ID: PILRB_HUMAN
• PDB ID: 4NFC; 4NFD
• Sequence:
  MGRPLLLPLLLLLQPPAFLQPGGSTGSGPSYLYGVTQPKHLSASMGGSVEIPFSFYYPWE
  LAIVPNVRISWRRGHFHGQSFYSTRPPSIHKDYVNRLFLNWTEGQESGFLRISNLRKEDQ
  SVYFCRVELDTRRSGRQQLQSIKGTKLTITQAVTTTTTWRPSSTTTIAGLRVTESKGHSE
  SWHLSLDTAIRVALAVAVLKTVILGLLCLLLLWWRRRKGSRAPSSDF
• Function: Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB is thought to act as a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface.
• KEGG Pathway:
  Virion - Herpesvirus (hsa03266)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Paired immunoglobulin-like type 2 receptor beta (PILRB).	[9]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [7] 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.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.