Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKQFX5H)

• DOT Name: Transcription factor Dp-2 (TFDP2)
• Synonyms: E2F dimerization partner 2
• Gene Name: TFDP2
• Related Disease:
  Chronic renal failure
  Parkinson disease
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Malignant mesothelioma
  Neoplasm
  Renal cell carcinoma
  Testicular germ cell tumor
  Chronic kidney disease
  Colorectal adenoma
• UniProt ID: TFDP2_HUMAN
• PDB ID: 1CF7
• Pfam ID: PF08781 ; PF02319
• Sequence:
  MTAKNVGLTSTNAEVRGFIDQNLSPTKGNISFVAFPVSNTNSPTKILPKTLGPINVNVGP
  QMIISTPQRLTSSGSVLIGSPYTPAPAMVTQTHIAEATGWVPGDRKRARKFIDSDFSESK
  RSKKGDKNGKGLRHFSMKVCEKVQRKGTTSYNEVADELVSEFTNSNNHLAADSAYDQKNI
  RRRVYDALNVLMAMNIISKEKKEIKWIGLPTNSAQECQNLEIEKQRRIERIKQKRAQLQE
  LLLQQIAFKNLVQRNRQNEQQNQGPPALNSTIQLPFIIINTSRKTVIDCSISSDKFEYLF
  NFDNTFEIHDDIEVLKRMGMSFGLESGKCSLEDLKLAKSLVPKALEGYITDISTGPSWLN
  QGLLLNSTQSVSNLDLTTGATLPQSSVNQGLCLDAEVALATGQFLAPNSHQSSSAASHCS
  ESRGETPCSFNDEDEEDDEEDSSSPE
• Function: Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The TFDP2:E2F complex functions in the control of cell-cycle progression from G1 to S phase. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters.
• Tissue Specificity: High levels in heart and skeletal muscle. Also found in placenta, kidney, brain, lung and liver. The presence as well as the abundance of the different transcripts appear to vary significantly in different tissues and cell lines.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  Inhibition of replication initiation of damaged DNA by RB1/E2F1 (R-HSA-113501)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  Activation of PUMA and translocation to mitochondria (R-HSA-139915)
  G0 and Early G1 (R-HSA-1538133)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  SMAD2/SMAD3 (R-HSA-2173796)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Oncogene Induced Senescence (R-HSA-2559585)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A (R-HSA-69656)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Activation of NOXA and translocation to mitochondria (R-HSA-111448)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[7]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[8]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[9]
Colorectal adenoma	DISTSVHM	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcription factor Dp-2 (TFDP2).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor Dp-2 (TFDP2).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor Dp-2 (TFDP2).	[13]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Transcription factor Dp-2 (TFDP2).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor Dp-2 (TFDP2).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor Dp-2 (TFDP2).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transcription factor Dp-2 (TFDP2).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Transcription factor Dp-2 (TFDP2).	[18]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Transcription factor Dp-2 (TFDP2).	[19]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transcription factor Dp-2 (TFDP2).	[20]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Transcription factor Dp-2 (TFDP2).	[21]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Transcription factor Dp-2 (TFDP2).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor Dp-2 (TFDP2).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor Dp-2 (TFDP2).	[24]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Transcription factor Dp-2 (TFDP2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor Dp-2 (TFDP2).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription factor Dp-2 (TFDP2).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor Dp-2 (TFDP2).	[27]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transcription factor Dp-2 (TFDP2).	[28]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Transcription factor Dp-2 (TFDP2).	[29]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE decreases the expression of Transcription factor Dp-2 (TFDP2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor Dp-2 (TFDP2).	[26]

References

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