Details of Drug Off-Target (DOT)

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

• DOT Name: Asialoglycoprotein receptor 2 (ASGR2)
• Synonyms: ASGP-R 2; ASGPR 2; C-type lectin domain family 4 member H2; Hepatic lectin H2; HL-2
• Gene Name: ASGR2
• UniProt ID: ASGR2_HUMAN
• Pfam ID: PF00059 ; PF03954
• Sequence:
  MAKDFQDIQQLSSEENDHPFHQGEGPGTRRLNPRRGNPFLKGPPPAQPLAQRLCSMVCFS
  LLALSFNILLLVVICVTGSQSEGHGGAQLQAELRSLKEAFSNFSSSTLTEVQAISTHGGS
  VGDKITSLGAKLEKQQQDLKADHDALLFHLKHFPVDLRFVACQMELLHSNGSQRTCCPVN
  WVEHQGSCYWFSHSGKAWAEAEKYCQLENAHLVVINSWEEQKFIVQHTNPFNTWIGLTDS
  DGSWKWVDGTDYRHNYKNWAVTQPDNWHGHELGGSEDCVEVQPDGRWNDDFCLQVYRWVC
  EKRRNATGEVA
• Function: Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.
• Tissue Specificity: Expressed exclusively in hepatic parenchymal cells.
• KEGG Pathway: Thyroid hormone synthesis (hsa04918)
• Reactome Pathway: Asparagine N-linked glycosylation (R-HSA-446203)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Asialoglycoprotein receptor 2 (ASGR2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Asialoglycoprotein receptor 2 (ASGR2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Asialoglycoprotein receptor 2 (ASGR2).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Asialoglycoprotein receptor 2 (ASGR2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Asialoglycoprotein receptor 2 (ASGR2).	[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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [8] 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.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.