Details of Drug Off-Target (DOT)

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

• DOT Name: CD99 antigen-like protein 2 (CD99L2)
• Synonyms: MIC2-like protein 1; CD antigen CD99
• Gene Name: CD99L2
• Related Disease:
  B-cell neoplasm
  Nervous system inflammation
• UniProt ID: C99L2_HUMAN
• Pfam ID: PF12301
• Sequence:
  MVAWRSAFLVCLAFSLATLVQRGSGDFDDFNLEDAVKETSSVKQPWDHTTTTTTNRPGTT
  RAPAKPPGSGLDLADALDDQDDGRRKPGIGGRERWNHVTTTTKRPVTTRAPANTLGNDFD
  LADALDDRNDRDDGRRKPIAGGGGFSDKDLEDIVGGGEYKPDKGKGDGRYGSNDDPGSGM
  VAEPGTIAGVASALAMALIGAVSSYISYQQKKFCFSIQQGLNADYVKGENLEAVVCEEPQ
  VKYSTLHTQSAEPPPPPEPARI
• Function: Plays a role in a late step of leukocyte extravasation helping cells to overcome the endothelial basement membrane. Acts at the same site as, but independently of, PECAM1. Homophilic adhesion molecule, but these interactions may not be required for cell aggregation.
• Tissue Specificity: Detected in cerebrospinal fluid (at protein level) . Expressed in many tissues, with low expression in thymus.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Leukocyte transendothelial migration (hsa04670)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[2]

3 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 CD99 antigen-like protein 2 (CD99L2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of CD99 antigen-like protein 2 (CD99L2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of CD99 antigen-like protein 2 (CD99L2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CD99 antigen-like protein 2 (CD99L2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CD99 antigen-like protein 2 (CD99L2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CD99 antigen-like protein 2 (CD99L2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CD99 antigen-like protein 2 (CD99L2).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of CD99 antigen-like protein 2 (CD99L2).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of CD99 antigen-like protein 2 (CD99L2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of CD99 antigen-like protein 2 (CD99L2).	[10]

References

• [1] Effect of shRNA targeting mouse CD99L2 gene in a murine B cell lymphoma in vitro and in vivo.Oncol Rep. 2013 Apr;29(4):1405-14. doi: 10.3892/or.2013.2244. Epub 2013 Jan 18.
• [2] CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation.J Leukoc Biol. 2018 Oct;104(4):787-797. doi: 10.1002/JLB.1A0617-228R. Epub 2018 May 23.
• [3] 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.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] 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.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.