Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOIB23)

• DOT Name: Protein CBFA2T2 (CBFA2T2)
• Synonyms: ETO homologous on chromosome 20; MTG8-like protein; MTG8-related protein 1; Myeloid translocation-related protein 1; p85
• Gene Name: CBFA2T2
• Related Disease:
  T-cell leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Chronic myelomonocytic leukaemia
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Glioblastoma multiforme
  Head and neck cancer
  Head and neck carcinoma
  HIV infectious disease
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Lymphoproliferative syndrome
  Malignant glioma
  Mood disorder
  Nasopharyngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Plasma cell myeloma
  Pneumococcal meningitis
  Polycythemia
  Primary familial polycythemia due to EPO receptor mutation
  Rabies
  Renal cell carcinoma
  Thymus lymphoma
  Kidney cancer
  Prostate carcinoma
  Renal carcinoma
  Small lymphocytic lymphoma
  Stroke
  Acute myelogenous leukaemia
  Advanced cancer
  Colorectal carcinoma
  Hepatitis C virus infection
  Mesothelioma
  Prostate cancer
• UniProt ID: MTG8R_HUMAN
• Pfam ID: PF08788 ; PF07531 ; PF01753
• Sequence:
  MAKESGISLKEIQVLARQWKVGPEKRVPAMPGSPVEVKIQSRSSPPTMPPLPPINPGGPR
  PVSFTPTALSNGINHSPPTLNGAPSPPQRFSNGPASSTSSALTNQQLPATCGARQLSKLK
  RFLTTLQQFGNDISPEIGEKVRTLVLALVNSTVTIEEFHCKLQEATNFPLRPFVIPFLKA
  NLPLLQRELLHCARAAKQTPSQYLAQHEHLLLNTSIASPADSSELLMEVHGNGKRPSPER
  REENSFDRDTIAPEPPAKRVCTISPAPRHSPALTVPLMNPGGQFHPTPPPLQHYTLEDIA
  TSHLYREPNKMLEHREVRDRHHSLGLNGGYQDELVDHRLTEREWADEWKHLDHALNCIME
  MVEKTRRSMAVLRRCQESDREELNYWKRRYNENTELRKTGTELVSRQHSPGSADSLSNDS
  QREFNSRPGTGYVPVEFWKKTEEAVNKVKIQAMSEVQKAVAEAEQKAFEVIATERARMEQ
  TIADVKRQAAEDAFLVINEQEESTENCWNCGRKASETCSGCNIARYCGSFCQHKDWERHH
  RLCGQNLHGQSPHGQGRPLLPVGRGSSARSADCSVPSPALDKTSATTSRSSTPASVTAID
  TNGL
• Function: Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency. Involved in primordial germ cell (PCG) formation. Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent manner. Can repress the expression of MMP7 in a ZBTB33-dependent manner. May function as a complex with the chimeric protein RUNX1/AML1-CBFA2T1/MTG8 (AML1-MTG8/ETO fusion protein) which is produced in acute myeloid leukemia with the chromosomal translocation t(8;21). May thus be involved in the repression of AML1-dependent transcription and the induction of G-CSF/CSF3-dependent cell growth. May be a tumor suppressor gene candidate involved in myeloid tumors with the deletion of the 20q11 region. Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes. Required for the maintenance of the secretory cell lineage in the small intestine. Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation.
• Tissue Specificity: Ubiquitously expressed in fetal and adult tissues. Highly expressed in adult brain, heart, lung, kidney, lymph node, appendix, thymus, testis, uterus, small intestine, prostate and thymus.
• Reactome Pathway: Specification of primordial germ cells (R-HSA-9827857)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell leukaemia	DISJ6YIF	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[6]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[8]
Colitis	DISAF7DD	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[11]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[11]
HIV infectious disease	DISO97HC	Strong	Biomarker	[12]
leukaemia	DISS7D1V	Strong	Altered Expression	[13]
Leukemia	DISNAKFL	Strong	Altered Expression	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Lymphoproliferative syndrome	DISMVL8O	Strong	Biomarker	[7]
Malignant glioma	DISFXKOV	Strong	Biomarker	[14]
Mood disorder	DISLVMWO	Strong	Biomarker	[15]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[19]
Pneumococcal meningitis	DISM5U0L	Strong	Biomarker	[20]
Polycythemia	DIS8B6VW	Strong	Genetic Variation	[21]
Primary familial polycythemia due to EPO receptor mutation	DISFVI97	Strong	Biomarker	[21]
Rabies	DISSC4V5	Strong	Biomarker	[20]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[8]
Thymus lymphoma	DISJ17C5	Strong	Biomarker	[7]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[22]
Renal carcinoma	DISER9XT	moderate	Altered Expression	[8]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[23]
Stroke	DISX6UHX	moderate	Biomarker	[24]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[25]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[26]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[27]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[28]
Prostate cancer	DISF190Y	Limited	Altered Expression	[22]

2 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 Protein CBFA2T2 (CBFA2T2).	[29]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein CBFA2T2 (CBFA2T2).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein CBFA2T2 (CBFA2T2).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein CBFA2T2 (CBFA2T2).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein CBFA2T2 (CBFA2T2).	[32]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein CBFA2T2 (CBFA2T2).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein CBFA2T2 (CBFA2T2).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein CBFA2T2 (CBFA2T2).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein CBFA2T2 (CBFA2T2).	[37]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Protein CBFA2T2 (CBFA2T2).	[38]

References

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• [8] Anticancer activity of Schiff base-Poloxamer P85 combination against kidney cancer.Int Urol Nephrol. 2018 Feb;50(2):247-255. doi: 10.1007/s11255-017-1782-9. Epub 2017 Dec 29.
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• [21] Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia.Blood. 2009 May 21;113(21):5287-97. doi: 10.1182/blood-2008-09-179572. Epub 2009 Mar 31.
• [22] LSD1 Activates PI3K/AKT Signaling Through Regulating p85 Expression in Prostate Cancer Cells.Front Oncol. 2019 Aug 2;9:721. doi: 10.3389/fonc.2019.00721. eCollection 2019.
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• [32] 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.
• [33] 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.
• [34] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [35] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
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