Details of Drug Off-Target (DOT)

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

• DOT Name: Band 4.1-like protein 5 (EPB41L5)
• Synonyms: Erythrocyte membrane protein band 4.1-like 5
• Gene Name: EPB41L5
• Related Disease:
  Metastatic malignant neoplasm
  Nephropathy
  Rheumatoid arthritis
  Kidney cancer
  Renal carcinoma
  Neuroendocrine neoplasm
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: E41L5_HUMAN
• Pfam ID: PF08736 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MLSFFRRTLGRRSMRKHAEKERLREAQRAATHIPAAGDSKSIITCRVSLLDGTDVSVDLP
  KKAKGQELFDQIMYHLDLIESDYFGLRFMDSAQVAHWLDGTKSIKKQVKIGSPYCLHLRV
  KFYSSEPNNLREELTRYLFVLQLKQDILSGKLDCPFDTAVQLAAYNLQAELGDYDLAEHS
  PELVSEFRFVPIQTEEMELAIFEKWKEYRGQTPAQAETNYLNKAKWLEMYGVDMHVVKAR
  DGNDYSLGLTPTGVLVFEGDTKIGLFFWPKITRLDFKKNKLTLVVVEDDDQGKEQEHTFV
  FRLDHPKACKHLWKCAVEHHAFFRLRGPVQKSSHRSGFIRLGSRFRYSGKTEYQTTKTNK
  ARRSTSFERRPSKRYSRRTLQMKACATKPEELSVHNNVSTQSNGSQQAWGMRSALPVSPS
  ISSAPVPVEIENLPQSPGTDQHDRKCIPLNIDLLNSPDLLEATIGDVIGASDTMETSQAL
  NDVNVATRLPGLGEPEVEYETLKDTSEKLKQLEMENSPLLSPRSNIDVNINSQEEVVKLT
  EKCLNNVIESPGLNVMRVPPDFKSNILKAQVEAVHKVTKEDSLLSHKNANVQDAATNSAV
  LNENNVPLPKESLETLMLITPADSGSVLKEATDELDALLASLTENLIDHTVAPQVSSTSM
  ITPRWIVPQSGAMSNGLAGCEMLLTGKEGHGNKDGISLISPPAPFLVDAVTSSGPILAEE
  AVLKQKCLLTTEL
• Function: Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[1]
Nephropathy	DISXWP4P	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[3]
Kidney cancer	DISBIPKM	Strong	Biomarker	[4]
Renal carcinoma	DISER9XT	Strong	Biomarker	[4]
Neuroendocrine neoplasm	DISNPLOO	Disputed	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[5]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Band 4.1-like protein 5 (EPB41L5).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Band 4.1-like protein 5 (EPB41L5).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Band 4.1-like protein 5 (EPB41L5).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Band 4.1-like protein 5 (EPB41L5).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Band 4.1-like protein 5 (EPB41L5).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Band 4.1-like protein 5 (EPB41L5).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Band 4.1-like protein 5 (EPB41L5).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Band 4.1-like protein 5 (EPB41L5).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Band 4.1-like protein 5 (EPB41L5).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Band 4.1-like protein 5 (EPB41L5).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Band 4.1-like protein 5 (EPB41L5).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Band 4.1-like protein 5 (EPB41L5).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Band 4.1-like protein 5 (EPB41L5).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Band 4.1-like protein 5 (EPB41L5).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Band 4.1-like protein 5 (EPB41L5).	[21]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Band 4.1-like protein 5 (EPB41L5).	[23]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Band 4.1-like protein 5 (EPB41L5).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Band 4.1-like protein 5 (EPB41L5).	[27]

References

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• [2] The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4621-E4630. doi: 10.1073/pnas.1617004114. Epub 2017 May 23.
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• [4] High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue.Cell Commun Signal. 2016 Nov 21;14(1):28. doi: 10.1186/s12964-016-0151-0.
• [5] EPB41L5 Mediates TGF-Induced Metastasis of Gastric Cancer.Clin Cancer Res. 2019 Jun 15;25(12):3617-3629. doi: 10.1158/1078-0432.CCR-18-2959. Epub 2019 Feb 27.
• [6] 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.
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• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] 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.
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• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] 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.
• [22] 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.
• [23] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [24] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [25] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [26] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [27] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.