Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4O23TK)

• DOT Name: Protein p13 MTCP-1 (MTCP1)
• Synonyms: p13MTCP1; Mature T-cell proliferation-1 type B1; MTCP-1 type B1
• Gene Name: MTCP1
• Related Disease:
  Ataxia-telangiectasia
  Leukemia
  Malignant glioma
  T lymphoblastic leukaemia
  Venous thromboembolism
  Neoplasm
  T-cell leukaemia
• UniProt ID: MTCP1_HUMAN
• PDB ID: 1A1X; 1QTT; 1QTU
• Pfam ID: PF01840
• Sequence:
  MAGEDVGAPPDHLWVHQEGIYRDEYQRTWVAVVEEETSFLRARVQQIQVPLGDAARPSHL
  LTSQLPLMWQLYPEERYMDNNSRLWQIQHHLMVRGVQELLLKLLPDD
• Function: Enhances the phosphorylation and activation of AKT1 and AKT2.
• Tissue Specificity: Not found at a significant level in any tissue.
• KEGG Pathway: PI3K-Akt sig.ling pathway (hsa04151)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia	DISP3EVR	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Genetic Variation	[2]
Malignant glioma	DISFXKOV	Strong	Biomarker	[3]
T lymphoblastic leukaemia	DIS2PNPP	Strong	Genetic Variation	[4]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]
T-cell leukaemia	DISJ6YIF	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein p13 MTCP-1 (MTCP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein p13 MTCP-1 (MTCP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein p13 MTCP-1 (MTCP1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein p13 MTCP-1 (MTCP1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein p13 MTCP-1 (MTCP1).	[12]

References

• [1] Expression of either the TCL1 oncogene, or transcripts from its homologue MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients.Oncogene. 1996 Jan 18;12(2):379-86.
• [2] Refined solution structure and backbone dynamics of 15N-labeled C12A-p8MTCP1 studied by NMR relaxation.J Biomol NMR. 1999 Dec;15(4):271-88. doi: 10.1023/a:1008336418418.
• [3] miR-126 Suppresses Invasion and Migration of Malignant Glioma by Targeting Mature T Cell Proliferation 1 (MTCP1).Med Sci Monit. 2018 Sep 20;24:6630-6637. doi: 10.12659/MSM.910292.
• [4] Reconstruction of rearranged T-cell receptor loci by whole genome and transcriptome sequencing gives insights into the initial steps of T-cell prolymphocytic leukemia.Genes Chromosomes Cancer. 2020 Apr;59(4):261-267. doi: 10.1002/gcc.22821. Epub 2019 Nov 29.
• [5] Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.Nat Genet. 2019 Nov;51(11):1574-1579. doi: 10.1038/s41588-019-0519-3. Epub 2019 Nov 1.
• [6] Abnormalities of chromosomes 8, 11, 14, and X in T-prolymphocytic leukemia studied by fluorescence in situ hybridization.Cancer Genet Cytogenet. 1998 Jun;103(2):110-6. doi: 10.1016/s0165-4608(97)00410-x.
• [7] Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia.Blood. 1998 Jul 15;92(2):368-73.
• [8] 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.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.