Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTFPZY2)

DOT Name Epidermal growth factor receptor substrate 15-like 1 (EPS15L1)
Synonyms Eps15-related protein; Eps15R
Gene Name EPS15L1
Related Disease
Multiple sclerosis ( )
Cornelia de Lange syndrome ( )
Hepatocellular carcinoma ( )
Split hand-foot malformation ( )
UniProt ID
EP15R_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12763
Sequence
MAAPLIPLSQQIPTGNSLYESYYKQVDPAYTGRVGASEAALFLKKSGLSDIILGKIWDLA
DPEGKGFLDKQGFYVALRLVACAQSGHEVTLSNLNLSMPPPKFHDTSSPLMVTPPSAEAH
WAVRVEEKAKFDGIFESLLPINGLLSGDKVKPVLMNSKLPLDVLGRVWDLSDIDKDGHLD
RDEFAVAMHLVYRALEKEPVPSALPPSLIPPSKRKKTVFPGAVPVLPASPPPKDSLRSTP
SHGSVSSLNSTGSLSPKHSLKQTQPTVNWVVPVADKMRFDEIFLKTDLDLDGYVSGQEVK
EIFMHSGLTQNLLAHIWALADTRQTGKLSKDQFALAMYFIQQKVSKGIDPPQVLSPDMVP
PSERGTPGPDSSGSLGSGEFTGVKELDDISQEIAQLQREKYSLEQDIREKEEAIRQKTSE
VQELQNDLDRETSSLQELEAQKQDAQDRLDEMDQQKAKLRDMLSDVRQKCQDETQMISSL
KTQIQSQESDLKSQEDDLNRAKSELNRLQQEETQLEQSIQAGRVQLETIIKSLKSTQDEI
NQARSKLSQLHESRQEAHRSLEQYDQVLDGAHGASLTDLANLSEGVSLAERGSFGAMDDP
FKNKALLFSNNTQELHPDPFQTEDPFKSDPFKGADPFKGDPFQNDPFAEQQTTSTDPFGG
DPFKESDPFRGSATDDFFKKQTKNDPFTSDPFTKNPSLPSKLDPFESSDPFSSSSVSSKG
SDPFGTLDPFGSGSFNSAEGFADFSQMSKPPPSGPFTSSLGGAGFSDDPFKSKQDTPALP
PKKPAPPRPKPPSGKSTPVSQLGSADFPEAPDPFQPLGADSGDPFQSKKGFGDPFSGKDP
FVPSSAAKPSKASASGFADFTSVS
Function
Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. 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.
KEGG Pathway
Endocytosis (hsa04144 )
Reactome Pathway
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
EGFR downregulation (R-HSA-182971 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Multiple sclerosis DISB2WZI Strong Genetic Variation [1]
Cornelia de Lange syndrome DISEQSXO moderate Genetic Variation [2]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [3]
Split hand-foot malformation DIS8PKGD Supportive Autosomal dominant [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [9]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [14]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [15]
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⏷ Show the Full List of 9 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [12]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [10]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Epidermal growth factor receptor substrate 15-like 1 (EPS15L1). [10]
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References

1 Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.Nat Genet. 2013 Nov;45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
2 Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange-like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome.Ann Hum Genet. 2019 Mar;83(2):100-109. doi: 10.1111/ahg.12289. Epub 2018 Oct 10.
3 A Noninvasive Prediction Nomogram for Lymph Node Metastasis of Hepatocellular Carcinoma Based on Serum Long Noncoding RNAs.Biomed Res Int. 2019 Jul 1;2019:1710670. doi: 10.1155/2019/1710670. eCollection 2019.
4 First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand/split-foot malformation. Clin Genet. 2018 Mar;93(3):699-702. doi: 10.1111/cge.13152. Epub 2018 Jan 25.
5 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.
6 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
7 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.
8 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.
9 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.
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 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.
12 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
13 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
15 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.