Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFMUX6O)

• DOT Name: Beta-2-glycoprotein 1 (APOH)
• Synonyms: APC inhibitor; Activated protein C-binding protein; Anticardiolipin cofactor; Apolipoprotein H; Apo-H; Beta-2-glycoprotein I; B2GPI; Beta(2)GPI
• Gene Name: APOH
• UniProt ID: APOH_HUMAN
• PDB ID: 1C1Z; 1G4F; 1G4G; 1QUB; 2KRI; 3OP8; 4JHS; 6V06; 6V08; 6V09; 6XSD; 6XST; 7JIK; 7KG4
• Pfam ID: PF00084 ; PF09014
• Sequence:
  MISPVLILFSSFLCHVAIAGRTCPKPDDLPFSTVVPLKTFYEPGEEITYSCKPGYVSRGG
  MRKFICPLTGLWPINTLKCTPRVCPFAGILENGAVRYTTFEYPNTISFSCNTGFYLNGAD
  SAKCTEEGKWSPELPVCAPIICPPPSIPTFATLRVYKPSAGNNSLYRDTAVFECLPQHAM
  FGNDTITCTTHGNWTKLPECREVKCPFPSRPDNGFVNYPAKPTLYYKDKATFGCHDGYSL
  DGPEEIECTKLGNWSAMPSCKASCKVPVKKATVVYQGERVKIQEKFKNGMLHGDKVSFFC
  KNKEKKCSYTEDAQCIDGTIEVPKCFKEHSSLAFWKTDASDVKPC
• Function: Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• KEGG Pathway: Cholesterol metabolism (hsa04979)
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Beta-2-glycoprotein 1 (APOH).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-2-glycoprotein 1 (APOH).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Beta-2-glycoprotein 1 (APOH).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-2-glycoprotein 1 (APOH).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Beta-2-glycoprotein 1 (APOH).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Beta-2-glycoprotein 1 (APOH).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Beta-2-glycoprotein 1 (APOH).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Beta-2-glycoprotein 1 (APOH).	[9]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Beta-2-glycoprotein 1 (APOH).	[10]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Beta-2-glycoprotein 1 (APOH).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Beta-2-glycoprotein 1 (APOH).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Beta-2-glycoprotein 1 (APOH).	[14]

2 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 Beta-2-glycoprotein 1 (APOH).	[6]
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the phosphorylation of Beta-2-glycoprotein 1 (APOH).	[11]

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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [10] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [11] Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. Proteomics Clin Appl. 2015 Oct;9(9-10):907-16. doi: 10.1002/prca.201400148. Epub 2015 May 15.
• [12] Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010 Jul;47(1):81-90.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] 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.