Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7N056G)

DOT Name Myristoylated alanine-rich C-kinase substrate (MARCKS)
Synonyms MARCKS; Protein kinase C substrate, 80 kDa protein, light chain; 80K-L protein; PKCSL
Gene Name MARCKS
UniProt ID
MARCS_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF02063
Sequence
MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQA
NGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPT
AAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGE
GGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQ
EAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEE
PAAAAASSACAAPSQEAQPECSPEAPPAEAAE
Function
Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes. Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis. During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages. Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton. Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane.
Tissue Specificity Detected in spermatozoa.
KEGG Pathway
Fc gamma R-mediated phagocytosis (hsa04666 )
MicroR.s in cancer (hsa05206 )
Reactome Pathway
Acetylcholine regulates insulin secretion (R-HSA-399997 )

Molecular Interaction Atlas (MIA) of This DOT

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 decreases the methylation of Myristoylated alanine-rich C-kinase substrate (MARCKS). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Myristoylated alanine-rich C-kinase substrate (MARCKS). [26]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS). [28]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS). [28]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS). [36]
------------------------------------------------------------------------------------
37 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [7]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [9]
Testosterone DM7HUNW Approved Testosterone increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [10]
Triclosan DMZUR4N Approved Triclosan increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [11]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [12]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [13]
Selenium DM25CGV Approved Selenium increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [14]
Progesterone DMUY35B Approved Progesterone decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [15]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [16]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [17]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [18]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [19]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [12]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [20]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [12]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [16]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [21]
Prednisolone DMQ8FR2 Approved Prednisolone decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [12]
Methylprednisolone DM4BDON Approved Methylprednisolone decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [12]
Dopamine DMPGUCF Approved Dopamine increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [22]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [23]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [24]
DNCB DMDTVYC Phase 2 DNCB increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [27]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [30]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [31]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [32]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [33]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [34]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of Myristoylated alanine-rich C-kinase substrate (MARCKS). [35]
------------------------------------------------------------------------------------
⏷ Show the Full List of 37 Drug(s)

References

1 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.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3 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.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 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.
8 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.
9 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
10 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
11 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
12 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
13 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
14 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
15 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
16 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
17 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
19 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
20 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
21 Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
22 Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis. Mol Biosyst. 2014 Jun;10(6):1332-44.
23 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
24 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.
25 MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2006 Aug;20(5):736-42.
26 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.
27 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.
28 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.
29 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
30 Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
31 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
32 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
33 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
34 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.
35 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
36 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.