Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGCFPV8)

DOT Name Protein 4.1 (EPB41)
Synonyms P4.1; 4.1R; Band 4.1; EPB4.1; Erythrocyte membrane protein band 4.1
Gene Name EPB41
Related Disease
Ependymoma ( )
Meningioma ( )
Breast cancer ( )
Breast carcinoma ( )
Elliptocytosis 1 ( )
Hepatocellular carcinoma ( )
Melanoma ( )
Pyropoikilocytosis, hereditary ( )
Substance abuse ( )
Neoplasm ( )
Neuroblastoma ( )
Hereditary elliptocytosis ( )
Acute myelogenous leukaemia ( )
UniProt ID
EPB41_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1GG3; 2RQ1; 3QIJ
Pfam ID
PF05902 ; PF08736 ; PF09380 ; PF00373 ; PF09379 ; PF04382
Sequence
MTTEKSLVTEAENSQHQQKEEGEEAINSGQQEPQQEESCQTAAEGDNWCEQKLKASNGDT
PTHEDLTKNKERTSESRGLSRLFSSFLKRPKSQVSEEEGKEVESDKEKGEGGQKEIEFGT
SLDEEIILKAPIAAPEPELKTDPSLDLHSLSSAETQPAQEELREDPDFEIKEGEGLEECS
KIEVKEESPQSKAETELKASQKPIRKHRNMHCKVSLLDDTVYECVVEKHAKGQDLLKRVC
EHLNLLEEDYFGLAIWDNATSKTWLDSAKEIKKQVRGVPWNFTFNVKFYPPDPAQLTEDI
TRYYLCLQLRQDIVAGRLPCSFATLALLGSYTIQSELGDYDPELHGVDYVSDFKLAPNQT
KELEEKVMELHKSYRSMTPAQADLEFLENAKKLSMYGVDLHKAKDLEGVDIILGVCSSGL
LVYKDKLRINRFPWPKVLKISYKRSSFFIKIRPGEQEQYESTIGFKLPSYRAAKKLWKVC
VEHHTFFRLTSTDTIPKSKFLALGSKFRYSGRTQAQTRQASALIDRPAPHFERTASKRAS
RSLDGAAAVDSADRSPRPTSAPAITQGQVAEGGVLDASAKKTVVPKAQKETVKAEVKKED
EPPEQAEPEPTEAWKVEKTHIEVTVPTSNGDQTQKLAEKTEDLIRMRKKKRERLDGENIY
IRHSNLMLEDLDKSQEEIKKHHASISELKKNFMESVPEPRPSEWDKRLSTHSPFRTLNIN
GQIPTGEGPPLVKTQTVTISDNANAVKSEIPTKDVPIVHTETKTITYEAAQTDDNSGDLD
PGVLLTAQTITSETPSSTTTTQITKTVKGGISETRIEKRIVITGDADIDHDQVLVQAIKE
AKEQHPDMSVTKVVVHQETEIADE
Function
Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.
Reactome Pathway
Neurexins and neuroligins (R-HSA-6794361 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ependymoma DISUMRNZ Definitive Altered Expression [1]
Meningioma DISPT4TG Definitive Altered Expression [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Elliptocytosis 1 DISYW4P6 Strong Autosomal dominant [4]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [5]
Melanoma DIS1RRCY Strong Biomarker [6]
Pyropoikilocytosis, hereditary DISZGN3B Strong Biomarker [7]
Substance abuse DIS327VW Strong Biomarker [8]
Neoplasm DISZKGEW moderate Biomarker [2]
Neuroblastoma DISVZBI4 moderate Biomarker [9]
Hereditary elliptocytosis DISA71F4 Supportive Autosomal dominant [10]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [11]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Protein 4.1 (EPB41). [12]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Protein 4.1 (EPB41). [16]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Protein 4.1 (EPB41). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Protein 4.1 (EPB41). [22]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Protein 4.1 (EPB41). [21]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Protein 4.1 (EPB41). [13]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Protein 4.1 (EPB41). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein 4.1 (EPB41). [15]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Protein 4.1 (EPB41). [17]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Protein 4.1 (EPB41). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Protein 4.1 (EPB41). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Protein 4.1 (EPB41). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein 4.1 (EPB41). [23]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Protein 4.1 (EPB41). [24]
9-hydroxyoctadecadienoic acid DM0FWNJ Investigative 9-hydroxyoctadecadienoic acid increases the expression of Protein 4.1 (EPB41). [25]
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⏷ Show the Full List of 10 Drug(s)

References

1 Alterations of protein 4.1 family members in ependymomas: a study of 84 cases.Mod Pathol. 2005 Jul;18(7):991-7. doi: 10.1038/modpathol.3800390.
2 GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.Cancer Genet Cytogenet. 2005 Oct 1;162(1):63-7. doi: 10.1016/j.cancergencyto.2005.02.009.
3 Expression of Protein 4.1 Family in Breast Cancer: Database Mining for 4.1 Family Members in Malignancies.Med Sci Monit. 2019 May 7;25:3374-3389. doi: 10.12659/MSM.914085.
4 Homozygous 4.1(-) hereditary elliptocytosis associated with a point mutation in the downstream initiation codon of protein 4.1 gene. J Clin Invest. 1992 Nov;90(5):1713-7. doi: 10.1172/JCI116044.
5 Integrative Functional Genomics Implicates EPB41 Dysregulation in Hepatocellular Carcinoma Risk.Am J Hum Genet. 2016 Aug 4;99(2):275-86. doi: 10.1016/j.ajhg.2016.05.029. Epub 2016 Jul 21.
6 Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
7 Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis.Blood Cells Mol Dis. 2016 Oct;61:4-9. doi: 10.1016/j.bcmd.2016.07.003. Epub 2016 Jul 17.
8 Gender-stratified gene and gene-treatment interactions in smoking cessation.Pharmacogenomics J. 2012 Dec;12(6):521-32. doi: 10.1038/tpj.2011.30. Epub 2011 Aug 2.
9 Reassignment of the EPB4.1 gene to 1p36 and assessment of its involvement in neuroblastomas.Eur J Clin Invest. 2001 Oct;31(10):907-14. doi: 10.1046/j.1365-2362.2001.00892.x.
10 Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013 Jul;27(4):167-78. doi: 10.1016/j.blre.2013.04.003. Epub 2013 May 9.
11 Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia.Exp Hematol. 2003 Nov;31(11):1066-72. doi: 10.1016/j.exphem.2003.08.003.
12 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.
13 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
14 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.
15 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
16 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
17 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.
18 Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
19 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
20 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.
21 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.
22 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.
23 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
24 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
25 A proteomic analysis of acute leukemia cells treated with 9-hydroxyoctadecadienoic acid. Lipids Health Dis. 2016 Nov 10;15(1):192. doi: 10.1186/s12944-016-0359-4.