Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM70AK1)

• DOT Name: TCF3 fusion partner (TFPT)
• Synonyms: INO80 complex subunit F; Protein FB1
• Gene Name: TFPT
• Related Disease:
  Rabies
  B-cell acute lymphoblastic leukaemia
  Childhood acute lymphoblastic leukemia
  leukaemia
  Leukemia
  Retinopathy
• UniProt ID: TFPT_HUMAN
• Sequence:
  MELEQREGTMAAVGFEEFSAPPGSELALPPLFGGHILESELETEVEFVSGGLGGSGLRER
  DEEEEAARGRRRRQRELNRRKYQALGRRCREIEQVNERVLNRLHQVQRITRRLQQERRFL
  MRVLDSYGDDYRASQFTIVLEDEGSQGTDAPTPGNAENEPPEKETLSPPRRTPAPPEPGS
  PAPGEGPSGRKRRRVPRDGRRAGNALTPELAPVQIKVEEDFGFEADEALDSSWVSRGPDK
  LLPYPTLASPASD
• Function: Appears to promote apoptosis in a p53/TP53-independent manner.; Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rabies	DISSC4V5	Definitive	Biomarker	[1]
B-cell acute lymphoblastic leukaemia	DISKLOKC	Strong	Genetic Variation	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Retinopathy	DISB4B0F	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of TCF3 fusion partner (TFPT).	[4]
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of TCF3 fusion partner (TFPT).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of TCF3 fusion partner (TFPT).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of TCF3 fusion partner (TFPT).	[7]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of TCF3 fusion partner (TFPT).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TCF3 fusion partner (TFPT).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TCF3 fusion partner (TFPT).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TCF3 fusion partner (TFPT).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TCF3 fusion partner (TFPT).	[9]

References

• [1] Ferret badger rabies in Zhejiang, Jiangxi and Taiwan, China.Arch Virol. 2019 Feb;164(2):579-584. doi: 10.1007/s00705-018-4082-5. Epub 2018 Nov 11.
• [2] Promoter analysis of TFPT (FB1), a molecular partner of TCF3 (E2A) in childhood acute lymphoblastic leukemia.Biochem Biophys Res Commun. 2001 Nov 16;288(5):1250-7. doi: 10.1006/bbrc.2001.5906.
• [3] Expression of PRPF31 and TFPT: regulation in health and retinal disease.Hum Mol Genet. 2012 Sep 15;21(18):4126-37. doi: 10.1093/hmg/dds242. Epub 2012 Jun 20.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.