Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTFHHU9)

• DOT Name: Ribosome quality control complex subunit TCF25 (TCF25)
• Synonyms: Nuclear localized protein 1; Transcription factor 25; TCF-25
• Gene Name: TCF25
• Related Disease:
  Myocardial infarction
  Neoplasm
• UniProt ID: TCF25_HUMAN
• Pfam ID: PF04910
• Sequence:
  MSRRALRRLRGEQRGQEPLGPGALHFDLRDDDDAEEEGPKRELGVRRPGGAGKEGVRVNN
  RFELINIDDLEDDPVVNGERSGCALTDAVAPGNKGRGQRGNTESKTDGDDTETVPSEQSH
  ASGKLRKKKKKQKNKKSSTGEASENGLEDIDRILERIEDSTGLNRPGPAPLSSRKHVLYV
  EHRHLNPDTELKRYFGARAILGEQRPRQRQRVYPKCTWLTTPKSTWPRYSKPGLSMRLLE
  SKKGLSFFAFEHSEEYQQAQHKFLVAVESMEPNNIVVLLQTSPYHVDSLLQLSDACRFQE
  DQEMARDLVERALYSMECAFHPLFSLTSGACRLDYRRPENRSFYLALYKQMSFLEKRGCP
  RTALEYCKLILSLEPDEDPLCMLLLIDHLALRARNYEYLIRLFQEWEAHRNLSQLPNFAF
  SVPLAYFLLSQQTDLPECEQSSARQKASLLIQQALTMFPGVLLPLLESCSVRPDASVSSH
  RFFGPNAEISQPPALSQLVNLYLGRSHFLWKEPATMSWLEENVHEVLQAVDAGDPAVEAC
  ENRRKVLYQRAPRNIHRHVILSEIKEAVAALPPDVTTQSVMGFDPLPPSDTIYSYVRPER
  LSPISHGNTIALFFRSLLPNYTMEGERPEEGVAGGLNRNQGLNRLMLAVRDMMANFHLND
  LEAPHEDDAEGEGEWD
• Function: Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation. In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1. Also acts as a transcriptional repressor: represses transcription of SRF in vitro and so may play a role in heart development. May play a role in cell death control.
• Tissue Specificity: In the embryo, widely expressed with highest levels in brain. In the adult, highest expression is found in the heart.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Disputed	Biomarker	[2]

2 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 Ribosome quality control complex subunit TCF25 (TCF25).	[3]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ribosome quality control complex subunit TCF25 (TCF25).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[4]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Ribosome quality control complex subunit TCF25 (TCF25).	[10]

References

• [1] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [2] Identification of prostate cancer antigens by automated high-throughput filter immunoscreening.J Immunol Methods. 2008 Jan 31;330(1-2):12-23. doi: 10.1016/j.jim.2007.10.011. Epub 2007 Nov 20.
• [3] 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.
• [4] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] 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.
• [10] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.