Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5VQMWY)

• DOT Name: Transcription factor E2F3 (E2F3)
• Synonyms: E2F-3
• Gene Name: E2F3
• UniProt ID: E2F3_HUMAN
• Pfam ID: PF16421 ; PF02319
• Sequence:
  MRKGIQPALEQYLVTAGGGEGAAVVAAAAAASMDKRALLASPGFAAAAAAAAAPGAYIQI
  LTTNTSTTSCSSSLQSGAVAAGPLLPSAPGAEQTAGSLLYTTPHGPSSRAGLLQQPPALG
  RGGSGGGGGPPAKRRLELGESGHQYLSDGLKTPKGKGRAALRSPDSPKTPKSPSEKTRYD
  TSLGLLTKKFIQLLSQSPDGVLDLNKAAEVLKVQKRRIYDITNVLEGIHLIKKKSKNNVQ
  WMGCSLSEDGGMLAQCQGLSKEVTELSQEEKKLDELIQSCTLDLKLLTEDSENQRLAYVT
  YQDIRKISGLKDQTVIVVKAPPETRLEVPDSIESLQIHLASTQGPIEVYLCPEETETHSP
  MKTNNQDHNGNIPKPASKDLASTNSGHSDCSVSMGNLSPLASPANLLQQTEDQIPSNLEG
  PFVNLLPPLLQEDYLLSLGEEEGISDLFDAYDLEKLPLVEDFMCS
• Function: Transcription activator that binds DNA cooperatively with DP proteins 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 DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner. Inhibits adipogenesis, probably through the repression of CEBPA binding to its target gene promoters.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  Cell cycle (hsa04110)
  Cellular senescence (hsa04218)
  Cushing syndrome (hsa04934)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Pancreatic cancer (hsa05212)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Bladder cancer (hsa05219)
  Chronic myeloid leukemia (hsa05220)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Oncogene Induced Senescence (R-HSA-2559585)
  G2 Phase (R-HSA-68911)
  Cyclin D associated events in G1 (R-HSA-69231)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

31 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 E2F3 (E2F3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription factor E2F3 (E2F3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor E2F3 (E2F3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor E2F3 (E2F3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor E2F3 (E2F3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor E2F3 (E2F3).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Transcription factor E2F3 (E2F3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor E2F3 (E2F3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor E2F3 (E2F3).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription factor E2F3 (E2F3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor E2F3 (E2F3).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor E2F3 (E2F3).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Transcription factor E2F3 (E2F3).	[12]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Transcription factor E2F3 (E2F3).	[13]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Transcription factor E2F3 (E2F3).	[14]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Transcription factor E2F3 (E2F3).	[15]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Transcription factor E2F3 (E2F3).	[15]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Transcription factor E2F3 (E2F3).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor E2F3 (E2F3).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor E2F3 (E2F3).	[18]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Transcription factor E2F3 (E2F3).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Transcription factor E2F3 (E2F3).	[20]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Transcription factor E2F3 (E2F3).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor E2F3 (E2F3).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transcription factor E2F3 (E2F3).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor E2F3 (E2F3).	[24]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transcription factor E2F3 (E2F3).	[26]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Transcription factor E2F3 (E2F3).	[27]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Transcription factor E2F3 (E2F3).	[28]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Transcription factor E2F3 (E2F3).	[29]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Transcription factor E2F3 (E2F3).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Transcription factor E2F3 (E2F3).	[25]

References

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• [22] Effect of bisphenol-A on the expression of selected genes involved in cell cycle and apoptosis in the OVCAR-3 cell line. Toxicol Lett. 2011 Apr 10;202(1):30-5. doi: 10.1016/j.toxlet.2011.01.015. Epub 2011 Jan 26.
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• [24] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
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