Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJ4J6G)

• DOT Name: Moesin (MSN)
• Synonyms: Membrane-organizing extension spike protein
• Gene Name: MSN
• Related Disease:
  Colorectal carcinoma
  Combined immunodeficiency due to moesin deficiency
  Adult glioblastoma
  Anaplastic large cell lymphoma
  Aplastic anemia
  Autism spectrum disorder
  B-cell lymphoma
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Diabetic kidney disease
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Huntington disease
  Inborn error of immunity
  Juvenile idiopathic arthritis
  Multiple sclerosis
  Myocardial ischemia
  Neurofibromatosis type 2
  Oral cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic tumour
  Retinoblastoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Systemic sclerosis
  Adenocarcinoma
  Colon carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Obesity
  Alopecia
  Breast neoplasm
  Melanoma
  Osteoarthritis
  Osteosarcoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MOES_HUMAN
• PDB ID: 1E5W; 1EF1; 1SGH; 6TXQ; 6TXS; 8CIR; 8CIS; 8CIT; 8CIU
• Pfam ID: PF00769 ; PF20492 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MPKTISVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWFFGLQYQDTKGFSTWLK
  LNKKVTAQDVRKESPLLFKFRAKFYPEDVSEELIQDITQRLFFLQVKEGILNDDIYCPPE
  TAVLLASYAVQSKYGDFNKEVHKSGYLAGDKLLPQRVLEQHKLNKDQWEERIQVWHEEHR
  GMLREDAVLEYLKIAQDLEMYGVNYFSIKNKKGSELWLGVDALGLNIYEQNDRLTPKIGF
  PWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILALCMGNHELYMRRRKPDTI
  EVQQMKAQAREEKHQKQMERAMLENEKKKREMAEKEKEKIEREKEELMERLKQIEEQTKK
  AQQELEEQTRRALELEQERKRAQSEAEKLAKERQEAEEAKEALLQASRDQKKTQEQLALE
  MAELTARISQLEMARQKKESEAVEWQQKAQMVQEDLEKTRAELKTAMSTPHVAEPAENEQ
  DEQDENGAEASADLRADAMAKDRSEEERTTEAEKNERVQKHLKALTSELANARDESKKTA
  NDMIHAENMRLGRDKYKTLRQIRQGNTKQRIDEFESM
• Function: Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton. Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement. These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs. Modulates phagolysosomal biogenesis in macrophages. Participates also in immunologic synapse formation.
• Tissue Specificity: In all tissues and cultured cells studied.
• KEGG Pathway:
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Measles (hsa05162)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Recycling pathway of L1 (R-HSA-437239)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Combined immunodeficiency due to moesin deficiency	DISTWK6G	Definitive	X-linked	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Biomarker	[4]
Aplastic anemia	DISJRSC0	Strong	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[11]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Huntington disease	DISQPLA4	Strong	Biomarker	[17]
Inborn error of immunity	DISNGCMN	Strong	Biomarker	[18]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[19]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[20]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[21]
Neurofibromatosis type 2	DISI8ECS	Strong	Biomarker	[22]
Oral cancer	DISLD42D	Strong	Biomarker	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[13]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[24]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[28]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[29]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[30]
Lung cancer	DISCM4YA	moderate	Biomarker	[31]
Lung carcinoma	DISTR26C	moderate	Biomarker	[31]
Obesity	DIS47Y1K	moderate	Biomarker	[32]
Alopecia	DIS37HU4	Limited	Genetic Variation	[33]
Breast neoplasm	DISNGJLM	Limited	Genetic Variation	[34]
Melanoma	DIS1RRCY	Limited	Biomarker	[35]
Osteoarthritis	DIS05URM	Limited	Biomarker	[36]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[8]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[37]
Prostate cancer	DISF190Y	Limited	Biomarker	[38]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[38]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Moesin (MSN).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Moesin (MSN).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Moesin (MSN).	[53]

14 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 Moesin (MSN).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Moesin (MSN).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Moesin (MSN).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Moesin (MSN).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Moesin (MSN).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Moesin (MSN).	[45]
Selenium	DM25CGV	Approved	Selenium increases the expression of Moesin (MSN).	[46]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Moesin (MSN).	[47]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Moesin (MSN).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Moesin (MSN).	[46]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Moesin (MSN).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Moesin (MSN).	[52]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Moesin (MSN).	[54]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Moesin (MSN).	[55]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Moesin (MSN).	[49]

References

• [1] Proteomic analysis reveals overexpression of moesin and cytokeratin 17 proteins in colorectal carcinoma.Oncol Rep. 2012 Mar;27(3):608-20. doi: 10.3892/or.2011.1545. Epub 2011 Nov 10.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Moesin Up-regulation Is Associated with Enhanced Tumor Progression Imaged Non-invasively in an Orthotopic Mouse Model of Human Glioblastoma.Anticancer Res. 2018 Jun;38(6):3267-3272. doi: 10.21873/anticanres.12591.
• [4] Heterogeneity of genomic breakpoints in MSN-ALK translocations in anaplastic large cell lymphoma.Hum Pathol. 2004 Aug;35(8):1038-41. doi: 10.1016/j.humpath.2004.05.006.
• [5] Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma.J Immunol. 2009 Jan 1;182(1):703-10. doi: 10.4049/jimmunol.182.1.703.
• [6] Brain enhancer activities at the gene-poor 5p14.1 autism-associated locus.Sci Rep. 2016 Aug 9;6:31227. doi: 10.1038/srep31227.
• [7] Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma.Leukemia. 2015 Sep;29(9):1857-67. doi: 10.1038/leu.2015.86. Epub 2015 Mar 24.
• [8] Ezrin and moesin expression in canine and feline osteosarcoma.Histol Histopathol. 2017 Aug;32(8):805-816. doi: 10.14670/HH-11-848. Epub 2016 Nov 30.
• [9] Moesin is an independent prognostic marker for ER-positive breast cancer.Oncol Lett. 2019 Feb;17(2):1921-1933. doi: 10.3892/ol.2018.9799. Epub 2018 Dec 6.
• [10] ZINC4085554 inhibits cancer cell adhesion by interfering with the interaction of Akt1 and FAK.Oncol Lett. 2019 Jun;17(6):5251-5260. doi: 10.3892/ol.2019.10192. Epub 2019 Mar 27.
• [11] Evaluation of associations between single nucleotide polymorphisms in the FRMD3 and CARS genes and diabetic nephropathy in a Kuwaiti population.Genet Mol Res. 2016 Jan 29;15(1). doi: 10.4238/gmr.15017619.
• [12] A monoclonal antibody (MSN-1) against a newly established uterine endometrial cancer cell line (SNG-II) and its application to immunohistochemistry and flow cytometry.Am J Obstet Gynecol. 1989 Oct;161(4):1079-86. doi: 10.1016/0002-9378(89)90787-4.
• [13] Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer.Br J Cancer. 2018 Oct;119(7):1-9. doi: 10.1038/s41416-018-0260-1. Epub 2018 Oct 5.
• [14] MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin.Theranostics. 2017 Apr 10;7(6):1663-1673. doi: 10.7150/thno.17886. eCollection 2017.
• [15] Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma.Biochem Biophys Res Commun. 2012 Feb 10;418(2):378-83. doi: 10.1016/j.bbrc.2012.01.030. Epub 2012 Jan 12.
• [16] Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier.Int J Nanomedicine. 2017 Jun 12;12:4361-4370. doi: 10.2147/IJN.S135626. eCollection 2017.
• [17] Genetically-directed Sparse Neuronal Labeling in BAC Transgenic Mice through Mononucleotide Repeat Frameshift.Sci Rep. 2017 Mar 8;7:43915. doi: 10.1038/srep43915.
• [18] Exome Sequencing Diagnoses X-Linked Moesin-Associated Immunodeficiency in a Primary Immunodeficiency Case.Front Immunol. 2018 Mar 5;9:420. doi: 10.3389/fimmu.2018.00420. eCollection 2018.
• [19] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [20] Oligodendrocyte degeneration and concomitant microglia activation directs peripheral immune cells into the forebrain.Neurochem Int. 2019 Jun;126:139-153. doi: 10.1016/j.neuint.2019.03.005. Epub 2019 Mar 10.
• [21] Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
• [22] VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation.Oncogene. 2008 Jul 3;27(29):4056-64. doi: 10.1038/onc.2008.44. Epub 2008 Mar 10.
• [23] Moesin expression by tumor cells is an unfavorable prognostic biomarker for oral cancer.BMC Cancer. 2018 Jan 8;18(1):53. doi: 10.1186/s12885-017-3914-0.
• [24] Proteomic profiling in pancreatic cancer with and without lymph node metastasis.Int J Cancer. 2009 Apr 1;124(7):1614-21. doi: 10.1002/ijc.24163.
• [25] EpCAM antibody-conjugated mesoporous silica nanoparticles to enhance the anticancer efficacy of carboplatin in retinoblastoma.Mater Sci Eng C Mater Biol Appl. 2017 Jul 1;76:646-651. doi: 10.1016/j.msec.2017.03.036. Epub 2017 Mar 6.
• [26] Moesin Involvement in Oral Carcinogenesis of the Lower Lip.Anticancer Res. 2018 May;38(5):2755-2760. doi: 10.21873/anticanres.12518.
• [27] The ERM Protein Moesin Regulates CD8(+) Regulatory T Cell Homeostasis and Self-Tolerance.J Immunol. 2017 Nov 15;199(10):3418-3426. doi: 10.4049/jimmunol.1700074. Epub 2017 Oct 4.
• [28] Semaphorin 4A enhances lung fibrosis through activation of Akt via PlexinD1 receptor.J Biosci. 2015 Dec;40(5):855-62. doi: 10.1007/s12038-015-9566-9.
• [29] Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.Cancer Biol Ther. 2005 May;4(5):596-601. doi: 10.4161/cbt.4.5.1748. Epub 2005 May 13.
• [30] Mutational analysis of the DAL-1/4.1B tumour-suppressor gene locus in meningiomas.Int J Mol Med. 2005 Oct;16(4):771-4.
• [31] Decoding c-Myc networks of cell cycle and apoptosis regulated genes in a transgenic mousemodel of papillary lung adenocarcinomas.Oncotarget. 2015 Oct 13;6(31):31569-92. doi: 10.18632/oncotarget.5035.
• [32] Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens core of female rats.Horm Behav. 2019 Nov;116:104583. doi: 10.1016/j.yhbeh.2019.104583. Epub 2019 Sep 10.
• [33] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [34] Microwave-Synthesized Platinum-Embedded Mesoporous Silica Nanoparticles as Dual-Modality Contrast Agents: Computed Tomography and Optical Imaging.Int J Mol Sci. 2019 Mar 28;20(7):1560. doi: 10.3390/ijms20071560.
• [35] Membrane-organizing protein moesin controls Treg differentiation and antitumor immunity via TGF- signaling.J Clin Invest. 2017 Apr 3;127(4):1321-1337. doi: 10.1172/JCI89281. Epub 2017 Mar 13.
• [36] Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
• [37] Correlations of Moesin expression with the pathological stage, nerve infiltration, tumor location and pain severity in patients with pancreatic cancer.J BUON. 2019 May-Jun;24(3):1225-1232.
• [38] G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer.Cancer Res. 2014 Jul 1;74(13):3489-500. doi: 10.1158/0008-5472.CAN-13-2708. Epub 2014 Apr 22.
• [39] 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.
• [40] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [41] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [42] 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.
• [43] Nuclear proteome analysis of cisplatin-treated HeLa cells. Mutat Res. 2010 Sep 10;691(1-2):1-8. doi: 10.1016/j.mrfmmm.2010.06.002. Epub 2010 Jun 9.
• [44] 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.
• [45] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [46] 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.
• [47] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [48] 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.
• [49] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [50] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [51] 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.
• [52] 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.
• [53] 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.
• [54] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [55] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.