Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NPP8U)

DOT Name Epidermal growth factor receptor substrate 15 (EPS15)
Synonyms Protein Eps15; Protein AF-1p
Gene Name EPS15
Related Disease
Thyroid gland papillary carcinoma ( )
Advanced cancer ( )
Bone osteosarcoma ( )
Hepatocellular carcinoma ( )
Lung neoplasm ( )
Neoplasm ( )
Osteosarcoma ( )
Promyelocytic leukaemia ( )
Non-small-cell lung cancer ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
UniProt ID
EPS15_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1C07; 1EH2; 1F8H; 1FF1; 2IV9; 2JXC; 4RH5; 4RH9; 4RHG; 4S0G; 5AWT; 5AWU; 5JP2
Pfam ID
PF12763
Sequence
MAAAAQLSLTQLSSGNPVYEKYYRQVDTGNTGRVLASDAAAFLKKSGLPDLILGKIWDLA
DTDGKGILNKQEFFVALRLVACAQNGLEVSLSSLNLAVPPPRFHDTSSPLLISGTSAAEL
PWAVKPEDKAKYDAIFDSLSPVNGFLSGDKVKPVLLNSKLPVDILGRVWELSDIDHDGML
DRDEFAVAMFLVYCALEKEPVPMSLPPALVPPSKRKTWVVSPAEKAKYDEIFLKTDKDMD
GFVSGLEVREIFLKTGLPSTLLAHIWSLCDTKDCGKLSKDQFALAFHLISQKLIKGIDPP
HVLTPEMIPPSDRASLQKNIIGSSPVADFSAIKELDTLNNEIVDLQREKNNVEQDLKEKE
DTIKQRTSEVQDLQDEVQRENTNLQKLQAQKQQVQELLDELDEQKAQLEEQLKEVRKKCA
EEAQLISSLKAELTSQESQISTYEEELAKAREELSRLQQETAELEESVESGKAQLEPLQQ
HLQDSQQEISSMQMKLMEMKDLENHNSQLNWCSSPHSILVNGATDYCSLSTSSSETANLN
EHVEGQSNLESEPIHQESPARSSPELLPSGVTDENEVTTAVTEKVCSELDNNRHSKEEDP
FNVDSSSLTGPVADTNLDFFQSDPFVGSDPFKDDPFGKIDPFGGDPFKGSDPFASDCFFR
QSTDPFATSSTDPFSAANNSSITSVETLKHNDPFAPGGTVVAASDSATDPFASVFGNESF
GGGFADFSTLSKVNNEDPFRSATSSSVSNVVITKNVFEETSVKSEDEPPALPPKIGTPTR
PCPLPPGKRSINKLDSPDPFKLNDPFQPFPGNDSPKEKDPEIFCDPFTSATTTTNKEADP
SNFANFSAYPSEEDMIEWAKRESEREEEQRLARLNQQEQEDLELAIALSKSEISEA
Function
Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.
Tissue Specificity Ubiquitously expressed.
KEGG Pathway
Endocytosis (hsa04144 )
Reactome Pathway
Negative regulation of MET activity (R-HSA-6807004 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360 )
EGFR downregulation (R-HSA-182971 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Thyroid gland papillary carcinoma DIS48YMM Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Bone osteosarcoma DIST1004 Strong Altered Expression [3]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [4]
Lung neoplasm DISVARNB Strong Posttranslational Modification [5]
Neoplasm DISZKGEW Strong Biomarker [6]
Osteosarcoma DISLQ7E2 Strong Altered Expression [3]
Promyelocytic leukaemia DISYGG13 Strong Genetic Variation [7]
Non-small-cell lung cancer DIS5Y6R9 moderate Biomarker [8]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [9]
Breast cancer DIS7DPX1 Limited Altered Expression [6]
Breast carcinoma DIS2UE88 Limited Altered Expression [6]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [10]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [12]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Epidermal growth factor receptor substrate 15 (EPS15). [15]
Marinol DM70IK5 Approved Marinol increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [16]
Gefitinib DM15F0X Approved Gefitinib increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [17]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [18]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 decreases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [21]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [23]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [24]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [25]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [18]
biochanin A DM0HPWY Investigative biochanin A decreases the expression of Epidermal growth factor receptor substrate 15 (EPS15). [26]
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⏷ Show the Full List of 15 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Epidermal growth factor receptor substrate 15 (EPS15). [19]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Epidermal growth factor receptor substrate 15 (EPS15). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Epidermal growth factor receptor substrate 15 (EPS15). [22]
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References

1 Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor.Oncol Lett. 2018 Oct;16(4):4263-4270. doi: 10.3892/ol.2018.9200. Epub 2018 Jul 24.
2 NF-B-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers.Cell Death Dis. 2018 Apr 1;9(4):418. doi: 10.1038/s41419-018-0447-7.
3 The expression of Eps15 homology domain 1 is negatively correlated with disease-free survival and overall survival of osteosarcoma patients.J Orthop Surg Res. 2019 Apr 11;14(1):103. doi: 10.1186/s13018-019-1137-6.
4 EPS15R, TASP1, and PRPF3 are novel disease candidate genes targeted by HNF4alpha splice variants in hepatocellular carcinomas.Gastroenterology. 2008 Apr;134(4):1191-202. doi: 10.1053/j.gastro.2008.01.027. Epub 2008 Jan 17.
5 Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation.Oncogene. 2015 Jul;34(29):3791-803. doi: 10.1038/onc.2014.312. Epub 2014 Sep 29.
6 Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.Tumour Biol. 2017 Feb;39(2):1010428317691010. doi: 10.1177/1010428317691010.
7 MLL/AF-1p fusion in therapy-related early pre-B acute lymphoblastic leukemia with t(1;11)(p32;q23) translocation developing in the relapse phase of acute promyelocytic leukemia.Int J Hematol. 2003 Dec;78(5):439-42. doi: 10.1007/BF02983817.
8 Mammalian Eps15 homology domain 1 potentiates angiogenesis of non-small cell lung cancer by regulating 2AR signaling.J Exp Clin Cancer Res. 2019 Apr 25;38(1):174. doi: 10.1186/s13046-019-1162-7.
9 The localization of the HRX/ALL1 protein to specific nuclear subdomains is altered by fusion with its eps15 translocation partner.Cancer Res. 1997 Mar 1;57(5):799-802.
10 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.
11 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
12 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
13 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.
14 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.
15 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
16 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
17 Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
18 Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
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 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.
21 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
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 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
24 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
25 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
26 Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.