Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT13J2FM)

DOT Name MARCKS-related protein (MARCKSL1)
Synonyms MARCKS-like protein 1; Macrophage myristoylated alanine-rich C kinase substrate; Mac-MARCKS; MacMARCKS
Gene Name MARCKSL1
Related Disease
Dilated cardiomyopathy ( )
Dilated cardiomyopathy 1A ( )
Hypertrophic cardiomyopathy ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Acute leukaemia ( )
Acute monocytic leukemia ( )
Autoimmune disease ( )
Breast cancer ( )
Cardiac failure ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Congestive heart failure ( )
Endometrial carcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Leukemia ( )
Lung carcinoma ( )
Mesothelioma ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Neural tube defect ( )
Non-small-cell lung cancer ( )
Plasma cell myeloma ( )
Prolymphocytic leukaemia ( )
Renal cell carcinoma ( )
Small lymphocytic lymphoma ( )
Stomach cancer ( )
Urinary bladder neoplasm ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Glioma ( )
Lung adenocarcinoma ( )
Non-hodgkin lymphoma ( )
Astrocytoma ( )
Adult lymphoma ( )
Breast carcinoma ( )
Carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Colorectal carcinoma ( )
Lung cancer ( )
Lymphoma ( )
Pediatric lymphoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
MRP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF02063
Sequence
MGSQSSKAPRGDVTAEEAAGASPAKANGQENGHVKSNGDLSPKGEGESPPVNGTDEAAGA
TGDAIEPAPPSQGAEAKGEVPPKETPKKKKKFSFKKPFKLSGLSFKRNRKEGGGDSSASS
PTEEEQEQGEIGACSDEGTAQEGKAAATPESQEPQAKGAEASAASEEEAGPQATEPSTPS
GPESGPTPASAEQNE
Function
Controls cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation. When unphosphorylated, induces cell migration. When phosphorylated by MAPK8, induces actin bundles formation and stabilization, thereby reducing actin plasticity, hence restricting cell movement, including neuronal migration. May be involved in coupling the protein kinase C and calmodulin signal transduction systems.
KEGG Pathway
Fc gamma R-mediated phagocytosis (hsa04666 )
Leishmaniasis (hsa05140 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Dilated cardiomyopathy DISX608J Definitive Genetic Variation [1]
Dilated cardiomyopathy 1A DIS0RK9Z Definitive Genetic Variation [1]
Hypertrophic cardiomyopathy DISQG2AI Definitive Biomarker [1]
Small-cell lung cancer DISK3LZD Definitive Biomarker [2]
Squamous cell carcinoma DISQVIFL Definitive Altered Expression [3]
Acute leukaemia DISDQFDI Strong Altered Expression [4]
Acute monocytic leukemia DIS28NEL Strong Altered Expression [5]
Autoimmune disease DISORMTM Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Cardiac failure DISDC067 Strong Biomarker [1]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [8]
Colon cancer DISVC52G Strong Altered Expression [9]
Colon carcinoma DISJYKUO Strong Altered Expression [9]
Congestive heart failure DIS32MEA Strong Biomarker [1]
Endometrial carcinoma DISXR5CY Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
Glioblastoma multiforme DISK8246 Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
leukaemia DISS7D1V Strong Altered Expression [14]
Leukemia DISNAKFL Strong Biomarker [15]
Lung carcinoma DISTR26C Strong Altered Expression [16]
Mesothelioma DISKWK9M Strong Altered Expression [17]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [18]
Nasopharyngeal carcinoma DISAOTQ0 Strong Altered Expression [19]
Neural tube defect DIS5J95E Strong Biomarker [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [21]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [22]
Prolymphocytic leukaemia DISDPPHX Strong Altered Expression [23]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [8]
Small lymphocytic lymphoma DIS30POX Strong Genetic Variation [24]
Stomach cancer DISKIJSX Strong Biomarker [11]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [25]
Acute lymphocytic leukaemia DISPX75S moderate Altered Expression [26]
Acute myelogenous leukaemia DISCSPTN moderate Altered Expression [27]
Glioma DIS5RPEH moderate Biomarker [28]
Lung adenocarcinoma DISD51WR moderate Altered Expression [3]
Non-hodgkin lymphoma DISS2Y8A moderate Biomarker [29]
Astrocytoma DISL3V18 Disputed Biomarker [12]
Adult lymphoma DISK8IZR Limited Biomarker [30]
Breast carcinoma DIS2UE88 Limited Altered Expression [7]
Carcinoma DISH9F1N Limited Biomarker [31]
Childhood acute lymphoblastic leukemia DISJ5D6U Limited Altered Expression [26]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [32]
Lung cancer DISCM4YA Limited Altered Expression [33]
Lymphoma DISN6V4S Limited Biomarker [30]
Pediatric lymphoma DIS51BK2 Limited Biomarker [30]
Prostate cancer DISF190Y Limited Altered Expression [34]
Prostate carcinoma DISMJPLE Limited Altered Expression [34]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of MARCKS-related protein (MARCKSL1). [35]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of MARCKS-related protein (MARCKSL1). [36]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of MARCKS-related protein (MARCKSL1). [37]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of MARCKS-related protein (MARCKSL1). [38]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of MARCKS-related protein (MARCKSL1). [39]
Temozolomide DMKECZD Approved Temozolomide increases the expression of MARCKS-related protein (MARCKSL1). [40]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of MARCKS-related protein (MARCKSL1). [41]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of MARCKS-related protein (MARCKSL1). [42]
Testosterone DM7HUNW Approved Testosterone increases the expression of MARCKS-related protein (MARCKSL1). [43]
Progesterone DMUY35B Approved Progesterone decreases the expression of MARCKS-related protein (MARCKSL1). [44]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of MARCKS-related protein (MARCKSL1). [45]
Mifepristone DMGZQEF Approved Mifepristone increases the expression of MARCKS-related protein (MARCKSL1). [46]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of MARCKS-related protein (MARCKSL1). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of MARCKS-related protein (MARCKSL1). [50]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of MARCKS-related protein (MARCKSL1). [51]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of MARCKS-related protein (MARCKSL1). [41]
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⏷ Show the Full List of 16 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 decreases the methylation of MARCKS-related protein (MARCKSL1). [48]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of MARCKS-related protein (MARCKSL1). [49]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of MARCKS-related protein (MARCKSL1). [49]
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References

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11 The expression and significance of P-glycoprotein, lung resistance protein and multidrug resistance-associated protein in gastric cancer.J Exp Clin Cancer Res. 2009 Nov 24;28(1):144. doi: 10.1186/1756-9966-28-144.
12 Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes.Neuroscience. 2008 Jun 23;154(2):541-50. doi: 10.1016/j.neuroscience.2008.03.054. Epub 2008 Apr 1.
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18 The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer.Breast Cancer Res Treat. 2012 Sep;135(2):381-90. doi: 10.1007/s10549-012-2155-9. Epub 2012 Jul 8.
19 FBW7 increases drug sensitivity to cisplatin in human nasopharyngeal carcinoma by downregulating the expression of multidrug resistance-associated protein.Tumour Biol. 2015 Jun;36(6):4197-202. doi: 10.1007/s13277-015-3056-4. Epub 2015 Jan 14.
20 MARCKS: a case of molecular exaptation?.Int J Biochem Cell Biol. 2000 May;32(5):475-9. doi: 10.1016/s1357-2725(99)00152-1.
21 Prognostic significance of miR-23b in combination with P-gp, MRP and LRP/MVP expression in non-small cell lung cancer.Neoplasma. 2016;63(4):576-87. doi: 10.4149/neo_2016_411.
22 Neither P-gp SNP variants, P-gp expression nor functional P-gp activity predicts MDR in a preliminary study of plasma cell myeloma.Cytometry B Clin Cytom. 2012 Jul;82(4):229-37. doi: 10.1002/cyto.b.21018. Epub 2012 Mar 29.
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24 Expression of the multidrug resistance-associated protein (mrp) gene in chronic lymphocytic leukemia.Leuk Lymphoma. 2002 Jan;43(1):153-8. doi: 10.1080/10428190210198.
25 Differential expression of multidrug resistancerelated proteins in adriamycinresistant (pumc?1/ADM) and parental (pumc?1) human bladder cancer cell lines.Mol Med Rep. 2016 Nov;14(5):4741-4746. doi: 10.3892/mmr.2016.5806. Epub 2016 Oct 5.
26 Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia.Sao Paulo Med J. 2004 Jul 1;122(4):166-71. doi: 10.1590/s1516-31802004000400007. Epub 2004 Nov 9.
27 CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age.Ann Hematol. 2007 May;86(5):329-37. doi: 10.1007/s00277-007-0269-7. Epub 2007 Mar 6.
28 Involvement of the glutathione S-conjugate compounds and the MRP protein in Tc-99m-tetrofosmin and Tc-99m-sestamibi uptake in glioma cell lines.Nucl Med Biol. 2000 Apr;27(3):299-307. doi: 10.1016/s0969-8051(00)00085-8.
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31 c-Jun N-terminal kinase phosphorylation of MARCKSL1 determines actin stability and migration in neurons and in cancer cells.Mol Cell Biol. 2012 Sep;32(17):3513-26. doi: 10.1128/MCB.00713-12. Epub 2012 Jul 2.
32 Multidrug resistance-associated protein (MRP) expression is correlated with expression of aberrant p53 protein in colorectal cancer.Eur J Cancer. 1999 Jun;35(6):935-8. doi: 10.1016/s0959-8049(99)00035-0.
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