Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA6UCWC)

• DOT Name: Transcription factor 15 (TCF15)
• Synonyms: TCF-15; Class A basic helix-loop-helix protein 40; bHLHa40; Paraxis; Protein bHLH-EC2
• Gene Name: TCF15
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Polycystic ovarian syndrome
• UniProt ID: TCF15_HUMAN
• Pfam ID: PF00010
• Sequence:
  MAFALLRPVGAHVLYPDVRLLSEDEENRSESDASDQSFGCCEGPEAARRGPGPGGGRRAG
  GGGGAGPVVVVRQRQAANARERDRTQSVNTAFTALRTLIPTEPVDRKLSKIETVRLASSY
  IAHLANVLLLGDSADDGQPCFRAAGSAKGAVPAAADGGRQPRSICTFCLSNQRKGGGRRD
  LGGSCLKVRGVAPLRGPRR
• Function: Early transcription factor that plays a key role in somitogenesis, paraxial mesoderm development and regulation of stem cell pluripotency. Essential for the mesenchymal to epithelial transition associated with somite formation. Required for somite morphogenesis, thereby regulating patterning of the axial skeleton and skeletal muscles. Required for proper localization of somite epithelium markers during the mesenchymal to epithelial transition. Also plays a key role in regulation of stem cell pluripotency. Promotes pluripotency exit of embryonic stem cells (ESCs) by priming ESCs for differentiation. Acts as a key regulator of self-renewal of hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long-term self-renewal. Together with MEOX2, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells. Acts by forming a heterodimer with another helix-loop-helix (bHLH) protein, such as TCF3/E12, that binds DNA on E-box motifs (5'-CANNTG-3') and activates transcription of target genes.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[1]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[1]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[2]

11 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 15 (TCF15).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor 15 (TCF15).	[3]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transcription factor 15 (TCF15).	[3]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transcription factor 15 (TCF15).	[3]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Transcription factor 15 (TCF15).	[3]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Transcription factor 15 (TCF15).	[3]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Transcription factor 15 (TCF15).	[3]
Abacavir	DMMN36E	Approved	Abacavir decreases the expression of Transcription factor 15 (TCF15).	[3]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol decreases the expression of Transcription factor 15 (TCF15).	[3]
Dabigatran	DMDI6R4	Approved	Dabigatran decreases the expression of Transcription factor 15 (TCF15).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Transcription factor 15 (TCF15).	[3]

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 affects the methylation of Transcription factor 15 (TCF15).	[4]

References

• [1] Cardiac Endothelial Cell Transcriptome.Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):566-574. doi: 10.1161/ATVBAHA.117.310549. Epub 2018 Jan 4.
• [2] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [3] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [4] 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.