Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5F18V3)

• DOT Name: Endosome-associated-trafficking regulator 1 (ENTR1)
• Synonyms: Antigen NY-CO-3; Serologically defined colon cancer antigen 3
• Gene Name: ENTR1
• Related Disease:
  Colon cancer
  Neoplasm
• UniProt ID: ENTR1_HUMAN
• Sequence:
  MSGYQRRPGATPLSRARSLAIPDAPAFYERRSCLPQLNCERPHGRDLDSPFFGIRPAFMC
  YVPSPVLASVGDTDFGYGKGKCSKQSPSGAHGTHFGDDRFEDLEEANPFSFREFLKTKNL
  GLSKEDPASRIYAKEASRHSLGLDHNSPPSQTGGYGLEYQQPFFEDPTGAGDLLDEEEDE
  DTGWSGAYLPSAIEQTHPERVPAGTSPCSTYLSFFSTPSELAGPESLPSWALSDTDSRVS
  PASPAGSPSADFAVHGESLGDRHLRTLQISYDALKDENSKLRRKLNEVQSFSEAQTEMVR
  TLERKLEAKMIKEESDYHDLESVVQQVEQNLELMTKRAVKAENHVVKLKQEISLLQAQVS
  NFQRENEALRCGQGASLTVVKQNADVALQNLRVVMNSAQASIKQLVSGAETLNLVAEILK
  SIDRISEVKDEEEDS
• Function: Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis. Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Involved in the regulation of cytokinesis; the function may involve PTPN13 and GIT1. Plays a role in the formation of cilia. Involved in cargo protein localization, such as PKD2, at primary cilia. Involved in the presentation of the tumor necrosis factor (TNF) receptor TNFRSF1A on the cell surface, and hence in the modulation of the TNF-induced apoptosis.
• Tissue Specificity: Expressed in the colon (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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 Endosome-associated-trafficking regulator 1 (ENTR1).	[2]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Endosome-associated-trafficking regulator 1 (ENTR1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[9]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Endosome-associated-trafficking regulator 1 (ENTR1).	[11]

References

• [1] The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis.Oncogene. 2013 Sep 26;32(39):4602-13. doi: 10.1038/onc.2012.485. Epub 2012 Oct 29.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] 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.
• [11] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.