Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLYO0DB)

• DOT Name: T-cell surface antigen CD2 (CD2)
• Synonyms: Erythrocyte receptor; LFA-2; LFA-3 receptor; Rosette receptor; T-cell surface antigen T11/Leu-5; CD antigen CD2
• Gene Name: CD2
• UniProt ID: CD2_HUMAN
• PDB ID: 1CDB; 1GYA; 1HNF; 1L2Z; 1QA9; 2J6O; 2J7I
• Pfam ID: PF05790 ; PF07686
• Sequence:
  MSFPCKFVASFLLIFNVSSKGAVSKEITNALETWGALGQDINLDIPSFQMSDDIDDIKWE
  KTSDKKKIAQFRKEKETFKEKDTYKLFKNGTLKIKHLKTDDQDIYKVSIYDTKGKNVLEK
  IFDLKIQERVSKPKISWTCINTTLTCEVMNGTDPELNLYQDGKHLKLSQRVITHKWTTSL
  SAKFKCTAGNKVSKESSVEPVSCPEKGLDIYLIIGICGGGSLLMVFVALLVFYITKRKKQ
  RSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSHRPPPP
  GHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN
• Function: CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function.
• Tissue Specificity: Expressed in natural killer cells (at protein level).
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

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 T-cell surface antigen CD2 (CD2).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of T-cell surface antigen CD2 (CD2).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of T-cell surface antigen CD2 (CD2).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of T-cell surface antigen CD2 (CD2).	[5]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of T-cell surface antigen CD2 (CD2).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of T-cell surface antigen CD2 (CD2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of T-cell surface antigen CD2 (CD2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of T-cell surface antigen CD2 (CD2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of T-cell surface antigen CD2 (CD2).	[7]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] 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.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [5] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [6] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [7] 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.
• [8] BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.