Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH7NA58)

• DOT Name: CD27 antigen (CD27)
• Synonyms: CD27L receptor; T-cell activation antigen CD27; T14; Tumor necrosis factor receptor superfamily member 7; CD antigen CD27
• Gene Name: CD27
• Related Disease:
  Lymphoproliferative syndrome 2
  Obsolete autosomal recessive lymphoproliferative disease
• UniProt ID: CD27_HUMAN
• PDB ID: 5TL5; 5TLJ; 5TLK; 7KX0; 8DS5
• Pfam ID: PF00020
• Sequence:
  MARPHPWWLCVLGTLVGLSATPAPKSCPERHYWAQGKLCCQMCEPGTFLVKDCDQHRKAA
  QCDPCIPGVSFSPDHHTRPHCESCRHCNSGLLVRNCTITANAECACRNGWQCRDKECTEC
  DPLPNPSLTARSSQALSPHPQPTHLPYVSEMLEARTAGHMQTLADFRQLPARTLSTHWPP
  QRSLCSSDFIRILVIFSGMFLVFTLAGALFLHQRRKYRSNKGESPVEPAEPCHYSCPREE
  EGSTIPIQEDYRKPEPACSP
• Function: Receptor for CD70/CD27L. May play a role in survival of activated T-cells. May play a role in apoptosis through association with SIVA1.
• Tissue Specificity: Found in most T-lymphocytes.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway: TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphoproliferative syndrome 2	DIS7OJMP	Strong	Autosomal recessive	[1]
Obsolete autosomal recessive lymphoproliferative disease	DIS20UEA	Supportive	Autosomal recessive	[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 CD27 antigen (CD27).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of CD27 antigen (CD27).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of CD27 antigen (CD27).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of CD27 antigen (CD27).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate affects the expression of CD27 antigen (CD27).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of CD27 antigen (CD27).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of CD27 antigen (CD27).	[8]
Menthol	DMG2KW7	Approved	Menthol increases the expression of CD27 antigen (CD27).	[9]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of CD27 antigen (CD27).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CD27 antigen (CD27).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CD27 antigen (CD27).	[13]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of CD27 antigen (CD27).	[14]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of CD27 antigen (CD27).	[15]

References

• [1] Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. J Allergy Clin Immunol. 2015 Sep;136(3):703-712.e10. doi: 10.1016/j.jaci.2015.02.022. Epub 2015 Apr 3.
• [2] CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol. 2012 Mar;129(3):787-793.e6. doi: 10.1016/j.jaci.2011.11.013. Epub 2011 Dec 24.
• [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] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [5] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [6] Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol. 2009 Mar;144(5):667-76. doi: 10.1111/j.1365-2141.2008.07504.x. Epub 2008 Nov 20.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
• [9] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [10] Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol. 2008 May 15;180(10):6988-96. doi: 10.4049/jimmunol.180.10.6988.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells. EXCLI J. 2020 Nov 4;19:1459-1476. doi: 10.17179/excli2020-2934. eCollection 2020.
• [14] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.
• [15] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.