Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0ALXSL)

• DOT Name: Osteoclast-associated immunoglobulin-like receptor (OSCAR)
• Synonyms: Osteoclast-associated receptor; hOSCAR; Polymeric immunoglobulin receptor 3; PIgR-3; PIgR3; Poly-Ig receptor 3
• Gene Name: OSCAR
• UniProt ID: OSCAR_HUMAN
• PDB ID: 5CJ8; 5CJB; 5EIQ; 5EIV
• Pfam ID: PF13895
• Sequence:
  MALVLILQLLTLWPLCHTDITPSVPPASYHPKPWLGAQPATVVTPGVNVTLRCRAPQPAW
  RFGLFKPGEIAPLLFRDVSSELAEFFLEEVTPAQGGIYRCCYRRPDWGPGVWSQPSDVLE
  LLVTEELPRPSLVALPGPVVGPGANVSLRCAGRLRNMSFVLYREGVAAPLQYRHSAQPWA
  DFTLLGARAPGTYSCYYHTPSAPYVLSQRSEVLVISWEGEGPEARPASSAPGMQAPGPPP
  SDPGAQAPSLSSFRPRGLVLQPLLPQTQDSWDPAPPPSDPGV
• Function: Regulator of osteoclastogenesis which plays an important bone-specific function in osteoclast differentiation.
• KEGG Pathway: Osteoclast differentiation (hsa04380)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Osteoclast-associated immunoglobulin-like receptor (OSCAR).	[10]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [10] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.