Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7SAOJP)

• DOT Name: Malignant T-cell-amplified sequence 1 (MCTS1)
• Synonyms: MCT-1; Multiple copies T-cell malignancies
• Gene Name: MCTS1
• Related Disease:
  Epilepsy
  Matthew-Wood syndrome
  Prostate cancer
  Prostate carcinoma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Plasma cell myeloma
  Squamous cell carcinoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  B-cell lymphoma
  Bone osteosarcoma
  Carcinoma
  Gastric cancer
  Neuroblastoma
  Osteosarcoma
  Stomach cancer
  T-cell lymphoma
  Adult glioblastoma
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Melanoma
  Non-hodgkin lymphoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Parkinson disease
• UniProt ID: MCTS1_HUMAN
• PDB ID: 3R90; 5ONS; 5VYC; 6MS4
• Pfam ID: PF17832 ; PF01472
• Sequence:
  MFKKFDEKENVSNCIQLKTSVIKGIKNQLIEQFPGIEPWLNQIMPKKDPVKIVRCHEHIE
  ILTVNGELLFFRQREGPFYPTLRLLHKYPFILPHQQVDKGAIKFVLSGANIMCPGLTSPG
  AKLYPAAVDTIVAIMAEGKQHALCVGVMKMSAEDIEKVNKGIGIENIHYLNDGLWHMKTY
  K
• Function: Anti-oncogene that plays a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constitutively expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role as translation enhancer; recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; up-regulates protein levels of BCL2L2, TFDP1, MRE11, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiple chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3. Involved in translation initiation; promotes aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.
• Tissue Specificity: Ubiquitous. Over-expressed in T-cell lymphoid cell lines and in non-Hodgkin lymphoma cell lines as well as in a subset of primary large B-cell lymphomas.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Genetic Variation	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[2]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Cervical cancer	DISFSHPF	Strong	Biomarker	[11]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[11]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[8]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
B-cell lymphoma	DISIH1YQ	moderate	Biomarker	[22]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[23]
Carcinoma	DISH9F1N	moderate	Biomarker	[24]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[25]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[26]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[23]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[25]
T-cell lymphoma	DISSXRTQ	moderate	Biomarker	[27]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[28]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[29]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[30]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[30]
Lymphoma	DISN6V4S	Limited	Altered Expression	[27]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Altered Expression	[22]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[32]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[33]
Parkinson disease	DISQVHKL	Limited	Biomarker	[34]

14 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 Malignant T-cell-amplified sequence 1 (MCTS1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[42]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[43]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[46]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[47]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Malignant T-cell-amplified sequence 1 (MCTS1).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Malignant T-cell-amplified sequence 1 (MCTS1).	[45]

References

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