Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPUZ5DE)

DOT Name	CD99 antigen (CD99)
Synonyms	12E7; E2 antigen; Protein MIC2; T-cell surface glycoprotein E2; CD antigen CD99
Gene Name	CD99
Related Disease	Acute lymphocytic leukaemia ( ) Adult glioblastoma ( ) Advanced cancer ( ) Astrocytoma ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Classic Hodgkin lymphoma ( ) Epithelial ovarian cancer ( ) Ewing sarcoma/peripheral primitive neuroectodermal tumor ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Hepatitis C virus infection ( ) Leukemia ( ) Lymphoma ( ) Malignant soft tissue neoplasm ( ) Myelodysplastic syndrome ( ) Neoplasm ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Osteosarcoma ( ) Ovarian cancer ( ) Primitive neuroectodermal tumor ( ) Prostate cancer ( ) Prostate carcinoma ( ) Sarcoma ( ) Stomach cancer ( ) Synovial sarcoma ( ) Toxoplasmosis ( ) X-linked retinoschisis ( ) Colon carcinoma ( ) leukaemia ( ) Adenocarcinoma ( ) Adult lymphoma ( ) B-cell neoplasm ( ) Chromosomal disorder ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Pediatric lymphoma ( ) Plasma cell myeloma ( )
UniProt ID	CD99_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7SFX
Pfam ID	PF12301
Sequence	MARGAALALLLFGLLGVLVAAPDGGFDLSDALPDNENKKPTAIPKKPSAGDDFDLGDAVV DGENDDPRPPNPPKPMPNPNPNHPSSSGSFSDADLADGVSGGEGKGGSDGGGSHRKEGEE ADAPGVIPGIVGAVVVAVAGAISSFIAYQKKKLCFKENAEQGEVDMESHRNANAEPAVQR TLLEK
Function	Involved in T-cell adhesion processes and in spontaneous rosette formation with erythrocytes. Plays a role in a late step of leukocyte extravasation helping leukocytes to overcome the endothelial basement membrane. Acts at the same site as, but independently of, PECAM1. Involved in T-cell adhesion processes.
KEGG Pathway	Cell adhesion molecules (hsa04514 ) Leukocyte transendothelial migration (hsa04670 )
Reactome Pathway	Cell surface interactions at the vascular wall (R-HSA-202733 ) Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute lymphocytic leukaemia	DISPX75S	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Ewing sarcoma/peripheral primitive neuroectodermal tumor	DISD4VQC	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Leukemia	DISNAKFL	Strong	Biomarker	[11]
Lymphoma	DISN6V4S	Strong	Altered Expression	[12]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[13]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Sarcoma	DISZDG3U	Strong	Altered Expression	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[5]
Toxoplasmosis	DISYP8FH	Strong	Genetic Variation	[19]
X-linked retinoschisis	DISKV7Y8	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[3]
leukaemia	DISS7D1V	moderate	Biomarker	[11]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[20]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[12]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[12]
Chromosomal disorder	DISM5BB5	Limited	Genetic Variation	[21]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[22]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[22]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[23]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[12]
Plasma cell myeloma	DIS0DFZ0	Limited	Altered Expression	[24]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	CD99 antigen (CD99) affects the response to substance of Methotrexate.	[35]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of CD99 antigen (CD99).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CD99 antigen (CD99).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of CD99 antigen (CD99).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CD99 antigen (CD99).	[28]
Selenium	DM25CGV	Approved	Selenium increases the expression of CD99 antigen (CD99).	[29]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CD99 antigen (CD99).	[30]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of CD99 antigen (CD99).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of CD99 antigen (CD99).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CD99 antigen (CD99).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CD99 antigen (CD99).	[34]
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⏷ Show the Full List of 10 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of CD99 antigen (CD99).	[32]
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References

1	CD99 expression is strongly associated with clinical outcome in children with B-cell precursor acute lymphoblastic leukaemia.Br J Haematol. 2019 Feb;184(3):418-423. doi: 10.1111/bjh.15683. Epub 2018 Nov 28.
2	CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion.Int J Mol Sci. 2019 Mar 6;20(5):1137. doi: 10.3390/ijms20051137.
3	Targeting Tumor Vascular CD99 Inhibits Tumor Growth.Front Immunol. 2019 Apr 2;10:651. doi: 10.3389/fimmu.2019.00651. eCollection 2019.
4	A splice variant of CD99 increases motility and MMP-9 expression of human breast cancer cells through the AKT-, ERK-, and JNK-dependent AP-1 activation signaling pathways.J Biol Chem. 2006 Nov 17;281(46):34833-47. doi: 10.1074/jbc.M605483200. Epub 2006 Sep 19.
5	Expression of TLE-1 and CD99 in Carcinoma: Pitfalls in Diagnosis of Synovial Sarcoma.Appl Immunohistochem Mol Morphol. 2018 Jul;26(6):368-373. doi: 10.1097/PAI.0000000000000436.
6	SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.PLoS One. 2015 May 22;10(5):e0127568. doi: 10.1371/journal.pone.0127568. eCollection 2015.
7	Nrf2 induced cisplatin resistance in ovarian cancer by promoting CD99 expression.Biochem Biophys Res Commun. 2019 Oct 22;518(4):698-705. doi: 10.1016/j.bbrc.2019.08.113. Epub 2019 Aug 28.
8	Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.Am J Surg Pathol. 2017 Jun;41(6):761-772. doi: 10.1097/PAS.0000000000000831.
9	Immunoreactivity of CD99 in stomach cancer.J Korean Med Sci. 2002 Aug;17(4):483-9. doi: 10.3346/jkms.2002.17.4.483.
10	CS-SELEX generates high-affinity ssDNA aptamers as molecular probes for hepatitis C virus envelope glycoprotein E2.PLoS One. 2009 Dec 3;4(12):e8142. doi: 10.1371/journal.pone.0008142.
11	Clinical and preclinical characterization of CD99 isoforms in acute myeloid leukemia.Haematologica. 2020 Apr;105(4):999-1012. doi: 10.3324/haematol.2018.207001. Epub 2019 Aug 1.
12	p53 expression in large B-cell lymphomas with MYC extra copies and CD99 expression in large B-cell lymphomas in relation to MYC status.Hum Pathol. 2019 Apr;86:21-31. doi: 10.1016/j.humpath.2018.11.015. Epub 2018 Nov 26.
13	Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes.Virchows Arch. 2017 Apr;470(4):373-380. doi: 10.1007/s00428-017-2072-8. Epub 2017 Feb 14.
14	Do preclinical studies suggest that CD99 is a potential therapeutic target in acute myeloid leukemia and the myelodysplastic syndromes?.Expert Opin Ther Targets. 2018 May;22(5):381-383. doi: 10.1080/14728222.2018.1464140. Epub 2018 Apr 20.
15	Adult neuroblastoma in the retroperitoneum: A case report.Medicine (Baltimore). 2018 Dec;97(51):e13750. doi: 10.1097/MD.0000000000013750.
16	CD99 is a novel prognostic stromal marker in non-small cell lung cancer.Int J Cancer. 2012 Nov 15;131(10):2264-73. doi: 10.1002/ijc.27518. Epub 2012 Apr 24.
17	Malignant glioma with primitive neuroectodermal tumor-like component (MG-PNET): novel microarray findings in a pediatric patient.Clin Neuropathol. 2016 Nov/Dec;35(6):353-367. doi: 10.5414/NP300942.
18	Androgen regulation of the human pseudoautosomal gene MIC2, a potential marker for prostate cancer.Mol Carcinog. 1998 Sep;23(1):13-9.
19	Toxoplasma gondii: DNA vaccination with genes encoding antigens MIC2, M2AP, AMA1 and BAG1 and evaluation of their immunogenic potential.Exp Parasitol. 2007 Jul;116(3):273-82. doi: 10.1016/j.exppara.2007.01.017. Epub 2007 Feb 1.
20	Clinical significance of CD99 down-regulation in gastric adenocarcinoma.Clin Cancer Res. 2007 May 1;13(9):2584-91. doi: 10.1158/1078-0432.CCR-06-1785.
21	Unusual myogenic and melanocytic differentiation of soft tissue pPNETs: an immunohistochemical and molecular study of 3 cases.Am J Surg Pathol. 2010 Jul;34(7):1002-6. doi: 10.1097/PAS.0b013e3181e03b81.
22	Cancer-associated mutations in the canonical cleavage site do not influence CD99 shedding by the metalloprotease meprin but alter cell migration in vitro.Oncotarget. 2017 Jul 4;8(33):54873-54888. doi: 10.18632/oncotarget.18966. eCollection 2017 Aug 15.
23	p53 and -Catenin Expression Predict Poorer Prognosis in Patients With Anaplastic Large-Cell Lymphoma.Clin Lymphoma Myeloma Leuk. 2019 Jul;19(7):e385-e392. doi: 10.1016/j.clml.2019.03.030. Epub 2019 Apr 5.
24	Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms.Mod Pathol. 2018 Jun;31(6):881-889. doi: 10.1038/s41379-018-0011-0. Epub 2018 Feb 5.
25	The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
26	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
27	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.
28	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
29	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
30	Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
31	Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
32	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
33	Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
34	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
35	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.