Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPOJID2)

• DOT Name: B-cell differentiation antigen CD72 (CD72)
• Synonyms: Lyb-2; CD antigen CD72
• Gene Name: CD72
• Related Disease:
  Acute myelogenous leukaemia
  Mast cell neoplasm
  Acute lymphocytic leukaemia
  Autoimmune disease
  Autoimmune thrombocytopenia
  Childhood acute lymphoblastic leukemia
  Idiopathic thrombocytopenic purpura
  Immune thrombocytopenia
  Lupus
  Mastocytosis
  Systemic lupus erythematosus
  Systemic sclerosis
  Type III hypersensitivity disease
• UniProt ID: CD72_HUMAN
• Pfam ID: PF00059
• Sequence:
  MAEAITYADLRFVKAPLKKSISSRLGQDPGADDDGEITYENVQVPAVLGVPSSLASSVLG
  DKAAVKSEQPTASWRAVTSPAVGRILPCRTTCLRYLLLGLLLTCLLLGVTAICLGVRYLQ
  VSQQLQQTNRVLEVTNSSLRQQLRLKITQLGQSAEDLQGSRRELAQSQEALQVEQRAHQA
  AEGQLQACQADRQKTKETLQSEEQQRRALEQKLSNMENRLKPFFTCGSADTCCPSGWIMH
  QKSCFYISLTSKNWQESQKQCETLSSKLATFSEIYPQSHSYYFLNSLLPNGGSGNSYWTG
  LSSNKDWKLTDDTQRTRTYAQSSKCNKVHKTWSWWTLESESCRSSLPYICEMTAFRFPD
• Function: Plays a role in B-cell proliferation and differentiation.
• Tissue Specificity: Pre-B-cells and B-cells but not terminally differentiated plasma cells.
• KEGG Pathway: B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway: Other semaphorin interactions (R-HSA-416700)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Mast cell neoplasm	DIS6NFMB	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Autoimmune thrombocytopenia	DISNF0OI	Strong	Altered Expression	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[2]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Altered Expression	[4]
Immune thrombocytopenia	DISVCBNS	Strong	Altered Expression	[4]
Lupus	DISOKJWA	Strong	Biomarker	[5]
Mastocytosis	DIS1TEE0	Strong	Biomarker	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[5]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[7]
Type III hypersensitivity disease	DISFL6YG	Strong	Biomarker	[8]

1 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 B-cell differentiation antigen CD72 (CD72).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of B-cell differentiation antigen CD72 (CD72).	[10]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of B-cell differentiation antigen CD72 (CD72).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of B-cell differentiation antigen CD72 (CD72).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of B-cell differentiation antigen CD72 (CD72).	[13]

References

• [1] CD72 regulates the growth of KIT-mutated leukemia cell line Kasumi-1.Sci Rep. 2013 Oct 4;3:2861. doi: 10.1038/srep02861.
• [2] G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells.Blood. 1992 Dec 1;80(11):2826-34.
• [3] Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates Immunoglobulin Production in Murine B Cells.Front Immunol. 2018 Mar 15;9:373. doi: 10.3389/fimmu.2018.00373. eCollection 2018.
• [4] Upregulation of CD72 expression on CD19(+) CD27(+) memory Bcells by CD40L in primary immune thrombocytopenia.Br J Haematol. 2017 Jul;178(2):308-318. doi: 10.1111/bjh.14671. Epub 2017 Apr 17.
• [5] CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus.Immune Netw. 2019 Feb 13;19(1):e1. doi: 10.4110/in.2019.19.e1. eCollection 2019 Feb.
• [6] CD72 negatively regulates KIT-mediated responses in human mast cells.J Immunol. 2010 Mar 1;184(5):2468-75. doi: 10.4049/jimmunol.0902450. Epub 2010 Jan 25.
• [7] Peripheral blood lymphocytes analysis detects CD100/SEMA4D alteration in systemic sclerosis patients.Autoimmunity. 2011 Aug;44(5):427-36. doi: 10.3109/08916934.2010.541171. Epub 2011 Jan 19.
• [8] CD22 and CD72 cooperatively contribute to the development of the reverse Arthus reaction model.J Dermatol Sci. 2019 Jul;95(1):36-43. doi: 10.1016/j.jdermsci.2019.06.005. Epub 2019 Jun 20.
• [9] 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.
• [10] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [11] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.