Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX4ERRK)

DOT Name RalBP1-associated Eps domain-containing protein 1 (REPS1)
Synonyms RalBP1-interacting protein 1
Gene Name REPS1
Related Disease
Breast neoplasm ( )
Leukemia ( )
Neurodegeneration with brain iron accumulation ( )
Neurodegeneration with brain iron accumulation 7 ( )
UniProt ID
REPS1_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
MEGLTLSDAEQKYYSDLFSYCDIESTKKVVVNGRVLELFRAAQLPNDVVLQIMELCGATR
LGYFGRSQFYIALKLVAVAQSGFPLRVESINTVKDLPLPRFVASKNEQESRHAASYSSDS
ENQGSYSGVIPPPPGRGQVKKGSVSHDTVQPRTSADAQEPASPVVSPQQSPPTSPHTWRK
HSRHPSGGNSERPLAGPGPFWSPFGEAQSGSSAGDAVWSGHSPPPPQENWVSFADTPPTS
TLLTMHPASVQDQTTVRTVASATTAIEIRRQSSSYDDPWKITDEQRQYYVNQFKTIQPDL
NGFIPGSAAKEFFTKSKLPILELSHIWELSDFDKDGALTLDEFCAAFHLVVARKNGYDLP
EKLPESLMPKLIDLEDSADVGDQPGEVGYSGSPAEAPPSKSPSMPSLNQTWPELNQSSEQ
WETFSERSSSSQTLTQFDSNIAPADPDTAIVHPVPIRMTPSKIHMQEMELKRTGSDHTNP
TSPLLVKPSDLLEENKINSSVKFASGNTVADGYSSSDSFTSDPEQIGSNVTRQRSHSGTS
PDNTAPPPPPPRPQPSHSRSSSLDMNRTFTVTTGQQQAGVVAHPPAVPPRPQPSQAPGPA
VHRPVDADGLITHTSTSPQQIPEQPNFADFSQFEVFAASNVNDEQDDEAEKHPEVLPAEK
ASDPASSLRVAKTDSKTEEKTAASAPANVSKGTTPLAPPPKPVRRRLKSEDELRPEVDEH
TQKTGVLAAVLASQPSIPRSVGKDKKAIQASIRRNKETNTVLARLNSELQQQLKDVLEER
ISLEVQLEQLRPFSHL
Function May coordinate the cellular actions of activated EGF receptors and Ral-GTPases.
Tissue Specificity Widely expressed with highest levels in heart and testis.
Reactome Pathway
Clathrin-mediated endocytosis (R-HSA-8856828 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast neoplasm DISNGJLM Strong Biomarker [1]
Leukemia DISNAKFL Strong Biomarker [2]
Neurodegeneration with brain iron accumulation DISRK4DZ Strong Genetic Variation [3]
Neurodegeneration with brain iron accumulation 7 DISUWETZ Limited Unknown [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 RalBP1-associated Eps domain-containing protein 1 (REPS1). [5]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of RalBP1-associated Eps domain-containing protein 1 (REPS1). [16]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of RalBP1-associated Eps domain-containing protein 1 (REPS1). [16]
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12 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 RalBP1-associated Eps domain-containing protein 1 (REPS1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [9]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [10]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [11]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [12]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [13]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of RalBP1-associated Eps domain-containing protein 1 (REPS1). [18]
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⏷ Show the Full List of 12 Drug(s)

References

1 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
2 RALBP1/RLIP76 mediates multidrug resistance.Int J Oncol. 2007 Jan;30(1):139-44.
3 Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. Am J Hum Genet. 2018 Feb 1;102(2):266-277. doi: 10.1016/j.ajhg.2018.01.003.
4 Adenosine 3':5'-monophosphate metabolism and turnover in dog thyroid slices. Eur J Biochem. 1977 Jan;72(2):241-6. doi: 10.1111/j.1432-1033.1977.tb11245.x.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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 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.
9 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.
10 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
11 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
12 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
13 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
14 Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
15 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.
16 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.
17 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
18 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.