Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8ZANE)

DOT Name	Emerin (EMD)
Gene Name	EMD
Related Disease	Arthritis ( ) Parkinsonian disorder ( ) Rheumatoid arthritis ( ) X-linked Emery-Dreifuss muscular dystrophy ( ) Acute myocardial infarction ( ) Advanced cancer ( ) Arrhythmia ( ) Atrial fibrillation ( ) Brain neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma ( ) Cardiac disease ( ) Cardiac failure ( ) Cerebral infarction ( ) Congestive heart failure ( ) Dilated cardiomyopathy ( ) Dilated cardiomyopathy 1A ( ) Duchenne muscular dystrophy ( ) Dystonia ( ) Emery-Dreifuss muscular dystrophy 2, autosomal dominant ( ) Graves disease ( ) Heart arrhythmia ( ) Herpes simplex infection ( ) High blood pressure ( ) leukaemia ( ) Leukemia ( ) Limb-girdle muscular dystrophy ( ) Lipodystrophy ( ) Lung adenocarcinoma ( ) Metabolic disorder ( ) Moyamoya disease ( ) Muscular dystrophy ( ) Myopathy ( ) Myositis disease ( ) Obesity ( ) Pancreatic cancer ( ) Pancreatic tumour ( ) Prostate cancer ( ) Prostate carcinoma ( ) Squamous cell carcinoma ( ) Ewing sarcoma ( ) Undifferentiated carcinoma ( ) Non-small-cell lung cancer ( ) Graft-versus-host disease ( ) Neoplasm ( ) Neuromuscular disease ( ) Premature aging syndrome ( ) Rectal carcinoma ( )
UniProt ID	EMD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1JEI; 2ODC; 2ODG; 6GHD; 6RPR; 7NDY
Pfam ID	PF03020
Sequence	MDNYADLSDTELTTLLRRYNIPHGPVVGSTRRLYEKKIFEYETQRRRLSPPSSSAASSYS FSDLNSTRGDADMYDLPKKEDALLYQSKGYNDDYYEESYFTTRTYGEPESAGPSRAVRQS VTSFPDADAFHHQVHDDDLLSSSEEECKDRERPMYGRDSAYQSITHYRPVSASRSSLDLS YYPTSSSTSFMSSSSSSSSWLTRRAIRPENRAPGAGLGQDRQVPLWGQLLLFLVFVIVLF FIYHFMQAEEGNPF
Function	Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD.
Tissue Specificity	Skeletal muscle, heart, colon, testis, ovary and pancreas.
KEGG Pathway	Cytoskeleton in muscle cells (hsa04820 ) Hypertrophic cardiomyopathy (hsa05410 ) Arrhythmogenic right ventricular cardiomyopathy (hsa05412 ) Dilated cardiomyopathy (hsa05414 )
Reactome Pathway	Initiation of Nuclear Envelope (NE) Reformation (R-HSA-2995383 ) Depolymerization of the Nuclear Lamina (R-HSA-4419969 ) RAC1 GTPase cycle (R-HSA-9013149 ) RAC2 GTPase cycle (R-HSA-9013404 ) RHOD GTPase cycle (R-HSA-9013405 ) RHOG GTPase cycle (R-HSA-9013408 ) RAC3 GTPase cycle (R-HSA-9013423 ) Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523 ) Nuclear Envelope Breakdown (R-HSA-2980766 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Parkinsonian disorder	DISHGY45	Definitive	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
X-linked Emery-Dreifuss muscular dystrophy	DISDPMZ3	Definitive	X-linked	[3]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Arrhythmia	DISFF2NI	Strong	Biomarker	[6]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[7]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Biomarker	[10]
Cardiac disease	DISVO1I5	Strong	Biomarker	[11]
Cardiac failure	DISDC067	Strong	Biomarker	[12]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[14]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[15]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[16]
Dystonia	DISJLFGW	Strong	Biomarker	[17]
Emery-Dreifuss muscular dystrophy 2, autosomal dominant	DIS4FT32	Strong	Genetic Variation	[18]
Graves disease	DISU4KOQ	Strong	Biomarker	[19]
Heart arrhythmia	DISLKUNL	Strong	X-linked	[20]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[21]
High blood pressure	DISY2OHH	Strong	Biomarker	[22]
leukaemia	DISS7D1V	Strong	Biomarker	[23]
Leukemia	DISNAKFL	Strong	Biomarker	[23]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Biomarker	[24]
Lipodystrophy	DIS3SGVD	Strong	Genetic Variation	[25]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[26]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[27]
Moyamoya disease	DISO62CA	Strong	Biomarker	[28]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[29]
Myopathy	DISOWG27	Strong	Biomarker	[24]
Myositis disease	DISCIXF0	Strong	Biomarker	[30]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[31]
Pancreatic tumour	DIS3U0LK	Strong	Genetic Variation	[31]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[10]
Ewing sarcoma	DISQYLV3	moderate	Biomarker	[32]
Undifferentiated carcinoma	DISIAZST	moderate	Altered Expression	[33]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[34]
Graft-versus-host disease	DIS0QADF	Limited	Biomarker	[35]
Neoplasm	DISZKGEW	Limited	Biomarker	[36]
Neuromuscular disease	DISQTIJZ	Limited	CausalMutation	[37]
Premature aging syndrome	DIS51AGT	Limited	Genetic Variation	[38]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[36]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Emerin (EMD).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Emerin (EMD).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Emerin (EMD).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Emerin (EMD).	[48]
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11 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 Emerin (EMD).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Emerin (EMD).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Emerin (EMD).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Emerin (EMD).	[43]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Emerin (EMD).	[44]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Emerin (EMD).	[45]
DNCB	DMDTVYC	Phase 2	DNCB affects the expression of Emerin (EMD).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Emerin (EMD).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Emerin (EMD).	[50]
acrolein	DMAMCSR	Investigative	acrolein affects the expression of Emerin (EMD).	[46]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate affects the expression of Emerin (EMD).	[46]
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⏷ Show the Full List of 11 Drug(s)

References

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5	Emerin Deregulation Links Nuclear Shape Instability to Metastatic Potential.Cancer Res. 2018 Nov 1;78(21):6086-6097. doi: 10.1158/0008-5472.CAN-18-0608. Epub 2018 Aug 28.
6	Tissue inhibitors of matrix metalloproteinases in serum are cardiac biomarkers in Emery-Dreifuss muscular dystrophy.Kardiol Pol. 2015;73(5):360-5. doi: 10.5603/KP.a2014.0243. Epub 2015 Jan 7.
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9	A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells.Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4700-5. doi: 10.1073/pnas.0409894102. Epub 2005 Mar 21.
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11	Emerin and the nuclear lamina in muscle and cardiac disease.Circ Res. 2008 Jul 3;103(1):16-23. doi: 10.1161/CIRCRESAHA.108.172197.
12	Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.Sci Rep. 2017 Mar 14;7:44312. doi: 10.1038/srep44312.
13	Incidence and Risk Factors of the Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis for Adult Moyamoya Disease.Cerebrovasc Dis. 2019;47(3-4):178-187. doi: 10.1159/000500802. Epub 2019 May 23.
14	Emery-Dreifuss muscular dystrophy: focal point nuclear envelope.Curr Opin Neurol. 2019 Oct;32(5):728-734. doi: 10.1097/WCO.0000000000000741.
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16	Does satellite cell dysfunction contribute to disease progression in Emery-Dreifuss muscular dystrophy?.Biochem Soc Trans. 2008 Dec;36(Pt 6):1344-9. doi: 10.1042/BST0361344.
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18	Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy.J Cell Sci. 2001 Dec;114(Pt 24):4447-57. doi: 10.1242/jcs.114.24.4447.
19	Mean peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis: a diagnostic meta-analysis.BMC Endocr Disord. 2019 Jun 6;19(1):56. doi: 10.1186/s12902-019-0388-x.
20	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
21	Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3.J Virol. 2007 Oct;81(19):10792-803. doi: 10.1128/JVI.00196-07. Epub 2007 Jul 25.
22	Metabolic and Cardiovascular Benefits and Risks of EMD386088-A 5-HT(6) Receptor Partial Agonist and Dopamine Transporter Inhibitor.Front Neurosci. 2017 Feb 8;11:50. doi: 10.3389/fnins.2017.00050. eCollection 2017.
23	The LEM domain proteins emerin and LAP2alpha are dispensable for human immunodeficiency virus type 1 and murine leukemia virus infections.J Virol. 2008 Jun;82(12):5860-8. doi: 10.1128/JVI.00076-08. Epub 2008 Apr 9.
24	Deficiency of emerin contributes differently to the pathogenesis of skeletal and cardiac muscles in LmnaH222P/H222P mutant mice.PLoS One. 2019 Aug 20;14(8):e0221512. doi: 10.1371/journal.pone.0221512. eCollection 2019.
25	Effect of pathogenic mis-sense mutations in lamin A on its interaction with emerin in vivo.J Cell Sci. 2003 Jul 15;116(Pt 14):3027-35. doi: 10.1242/jcs.00599. Epub 2003 Jun 3.
26	Image analysis of the nuclear characteristics of emerin protein and the correlation with nuclear grooves and intranuclear cytoplasmic inclusions in lung adenocarcinoma.Oncol Rep. 2019 Jan;41(1):133-142. doi: 10.3892/or.2018.6848. Epub 2018 Nov 2.
27	Rare BANF1 Alleles and Relatively Frequent EMD Alleles Including 'Healthy Lipid' Emerin p.D149H in the ExAC Cohort.Front Cell Dev Biol. 2019 Apr 5;7:48. doi: 10.3389/fcell.2019.00048. eCollection 2019.
28	Surgical Revascularization: Ligation of Extracranial Internal Carotid Artery and Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Patient with Extracranial Internal Carotid Aneurysm and Hemorrhagic Moyamoya Disease.World Neurosurg. 2019 Jun;126:129-133. doi: 10.1016/j.wneu.2019.02.110. Epub 2019 Mar 1.
29	Postnatal development of mice with combined genetic depletions of lamin A/C, emerin and lamina-associated polypeptide 1.Hum Mol Genet. 2019 Aug 1;28(15):2486-2500. doi: 10.1093/hmg/ddz082.
30	Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis.Muscle Nerve. 2006 Oct;34(4):406-16. doi: 10.1002/mus.20584.
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34	A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC).Ann Oncol. 2006 Jun;17(6):1007-13. doi: 10.1093/annonc/mdl042. Epub 2006 Mar 13.
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36	T3 subclassification using the EMD/mesorectum ratio predicts neoadjuvant chemoradiation outcome in T3 rectal cancer patients.Br J Radiol. 2018 Jan;91(1081):20170617. doi: 10.1259/bjr.20170617. Epub 2017 Nov 21.
37	Co-morbidity of Emery-Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred.Eur J Neurol. 2007 Mar;14(3):305-8. doi: 10.1111/j.1468-1331.2006.01657.x.
38	Primary laminopathy fibroblasts display altered genome organization and apoptosis.Aging Cell. 2007 Apr;6(2):139-53. doi: 10.1111/j.1474-9726.2007.00270.x. Epub 2007 Feb 5.
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