General Information of Drug Off-Target (DOT) (ID: OTFSO7PG)

DOT Name Elastin (ELN)
Synonyms Tropoelastin
Gene Name ELN
Related Disease
Abdominal aortic aneurysm ( )
Arterial disorder ( )
Cutis laxa, autosomal dominant 1 ( )
Marfan syndrome ( )
Supravalvular aortic stenosis ( )
Aortic aneurysm ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autism ( )
Autosomal recessive polycystic kidney disease ( )
Cardiovascular disease ( )
Costello syndrome ( )
Depression ( )
facioscapulohumeral muscular dystrophy ( )
Fetal growth restriction ( )
Glaucoma/ocular hypertension ( )
High blood pressure ( )
Hypertrophic cardiomyopathy ( )
Liver cirrhosis ( )
Myocardial infarction ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Pulmonary emphysema ( )
Skin disease ( )
Stroke ( )
Subarachnoid hemorrhage ( )
Acute myelogenous leukaemia ( )
Chronic obstructive pulmonary disease ( )
Autosomal dominant cutis laxa ( )
Type-1/2 diabetes ( )
Artery stenosis ( )
Buschke-Ollendorff syndrome ( )
Familial thoracic aortic aneurysm and aortic dissection ( )
Hypercalcaemia ( )
Intellectual disability ( )
Moyamoya disease ( )
Myocardial ischemia ( )
Pneumothorax ( )
Pseudoxanthoma elasticum ( )
Pulmonary disease ( )
Pulmonary fibrosis ( )
UniProt ID
ELN_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MAGLTAAAPRPGVLLLLLSILHPSRPGGVPGAIPGGVPGGVFYPGAGLGALGGGALGPGG
KPLKPVPGGLAGAGLGAGLGAFPAVTFPGALVPGGVADAAAAYKAAKAGAGLGGVPGVGG
LGVSAGAVVPQPGAGVKPGKVPGVGLPGVYPGGVLPGARFPGVGVLPGVPTGAGVKPKAP
GVGGAFAGIPGVGPFGGPQPGVPLGYPIKAPKLPGGYGLPYTTGKLPYGYGPGGVAGAAG
KAGYPTGTGVGPQAAAAAAAKAAAKFGAGAAGVLPGVGGAGVPGVPGAIPGIGGIAGVGT
PAAAAAAAAAAKAAKYGAAAGLVPGGPGFGPGVVGVPGAGVPGVGVPGAGIPVVPGAGIP
GAAVPGVVSPEAAAKAAAKAAKYGARPGVGVGGIPTYGVGAGGFPGFGVGVGGIPGVAGV
PGVGGVPGVGGVPGVGISPEAQAAAAAKAAKYGAAGAGVLGGLVPGAPGAVPGVPGTGGV
PGVGTPAAAAAKAAAKAAQFGLVPGVGVAPGVGVAPGVGVAPGVGLAPGVGVAPGVGVAP
GVGVAPGIGPGGVAAAAKSAAKVAAKAQLRAAAGLGAGIPGLGVGVGVPGLGVGAGVPGL
GVGAGVPGFGAGADEGVRRSLSPELREGDPSSSQHLPSTPSSPRVPGALAAAKAAKYGAA
VPGVLGGLGALGGVGIPGGVVGAGPAAAAAAAKAAAKAAQFGLVGAAGLGGLGVGGLGVP
GVGGLGGIPPAAAAKAAKYGAAGLGGVLGGAGQFPLGGVAARPGFGLSPIFPGGACLGKA
CGRKRK
Function
Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle.
Tissue Specificity Expressed within the outer myometrial smooth muscle and throughout the arteriolar tree of uterus (at protein level). Also expressed in the large arteries, lung and skin.
KEGG Pathway
Cytoskeleton in muscle cells (hsa04820 )
Protein digestion and absorption (hsa04974 )
Reactome Pathway
Elastic fibre formation (R-HSA-1566948 )
Molecules associated with elastic fibres (R-HSA-2129379 )
Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Abdominal aortic aneurysm DISD06OF Definitive Biomarker [1]
Arterial disorder DISLG4XS Definitive Biomarker [2]
Cutis laxa, autosomal dominant 1 DISZR0A4 Definitive Autosomal dominant [3]
Marfan syndrome DISVEUWZ Definitive Biomarker [4]
Supravalvular aortic stenosis DIS8FSJD Definitive Autosomal dominant [5]
Aortic aneurysm DISQ5KRA Strong Altered Expression [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Autism DISV4V1Z Strong Biomarker [8]
Autosomal recessive polycystic kidney disease DISPUS40 Strong Biomarker [9]
Cardiovascular disease DIS2IQDX Strong Biomarker [10]
Costello syndrome DISXVJH3 Strong Posttranslational Modification [11]
Depression DIS3XJ69 Strong Genetic Variation [12]
facioscapulohumeral muscular dystrophy DISSE0H0 Strong Biomarker [13]
Fetal growth restriction DIS5WEJ5 Strong Biomarker [14]
Glaucoma/ocular hypertension DISLBXBY Strong Genetic Variation [15]
High blood pressure DISY2OHH Strong Biomarker [16]
Hypertrophic cardiomyopathy DISQG2AI Strong Altered Expression [17]
Liver cirrhosis DIS4G1GX Strong Biomarker [18]
Myocardial infarction DIS655KI Strong Biomarker [19]
Neoplasm DISZKGEW Strong Biomarker [20]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [21]
Obesity DIS47Y1K Strong Altered Expression [22]
Pulmonary emphysema DIS5M7HZ Strong Biomarker [23]
Skin disease DISDW8R6 Strong Biomarker [24]
Stroke DISX6UHX Strong Biomarker [25]
Subarachnoid hemorrhage DISI7I8Y Strong Genetic Variation [26]
Acute myelogenous leukaemia DISCSPTN moderate Biomarker [27]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [28]
Autosomal dominant cutis laxa DIS2180B Supportive Autosomal dominant [29]
Type-1/2 diabetes DISIUHAP Disputed Biomarker [30]
Artery stenosis DISQU4Q5 Limited Genetic Variation [31]
Buschke-Ollendorff syndrome DIS9J6VP Limited Biomarker [32]
Familial thoracic aortic aneurysm and aortic dissection DIS069FB Limited Genetic Variation [33]
Hypercalcaemia DISKQ2K7 Limited Genetic Variation [34]
Intellectual disability DISMBNXP Limited Genetic Variation [34]
Moyamoya disease DISO62CA Limited Genetic Variation [35]
Myocardial ischemia DISFTVXF Limited Biomarker [36]
Pneumothorax DISP86H1 Limited Biomarker [37]
Pseudoxanthoma elasticum DIS8WUQG Limited Biomarker [38]
Pulmonary disease DIS6060I Limited Biomarker [39]
Pulmonary fibrosis DISQKVLA Limited Biomarker [40]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Ifosfamide DMCT3I8 Approved Elastin (ELN) increases the Arterial disorder ADR of Ifosfamide. [53]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Elastin (ELN). [41]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Elastin (ELN). [42]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Elastin (ELN). [43]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Elastin (ELN). [44]
Fluorouracil DMUM7HZ Approved Fluorouracil affects the expression of Elastin (ELN). [45]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Elastin (ELN). [46]
Palbociclib DMD7L94 Approved Palbociclib increases the expression of Elastin (ELN). [11]
Etretinate DM2CZFA Approved Etretinate increases the expression of Elastin (ELN). [48]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Elastin (ELN). [51]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Elastin (ELN). [52]
Purvalanol A DMNQ7TM Investigative Purvalanol A decreases the expression of Elastin (ELN). [11]
CVT-313 DMSEK5W Investigative CVT-313 decreases the expression of Elastin (ELN). [11]
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⏷ Show the Full List of 12 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Penicillamine DM40EF6 Approved Penicillamine affects the localization of Elastin (ELN). [49]
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1 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 Elastin (ELN). [50]
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References

1 Mechanisms underlying the inhibitory effects of probucol on elastase-induced abdominal aortic aneurysm in mice.Br J Pharmacol. 2020 Jan;177(1):204-216. doi: 10.1111/bph.14857. Epub 2019 Nov 3.
2 Long-term Surgical Prognosis of Primary Supravalvular Aortic Stenosis Repair.Ann Thorac Surg. 2019 Oct;108(4):1202-1209. doi: 10.1016/j.athoracsur.2019.04.094. Epub 2019 Jun 20.
3 New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations. Hum Mutat. 2011 Apr;32(4):445-55. doi: 10.1002/humu.21462. Epub 2011 Mar 1.
4 Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation.J Cell Mol Med. 2019 Oct;23(10):7000-7009. doi: 10.1111/jcmm.14587. Epub 2019 Aug 11.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 Mesenchymal stem cell-derived conditioned medium attenuate angiotensin II-induced aortic aneurysm growth by modulating macrophage polarization.J Cell Mol Med. 2019 Dec;23(12):8233-8245. doi: 10.1111/jcmm.14694. Epub 2019 Oct 4.
7 Fractal dimension and directional analysis of elastic and collagen fiber arrangement in unsectioned arterial tissues affected by atherosclerosis and aging.J Appl Physiol (1985). 2019 Mar 1;126(3):638-646. doi: 10.1152/japplphysiol.00497.2018. Epub 2019 Jan 10.
8 Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits.Eur J Hum Genet. 2014 Jan;22(1):64-70. doi: 10.1038/ejhg.2013.101. Epub 2013 Jun 12.
9 Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model.Am J Physiol Renal Physiol. 2011 Jun;300(6):F1431-6. doi: 10.1152/ajprenal.00079.2011. Epub 2011 Apr 6.
10 Role of elastin peptides and elastin receptor complex in metabolic and cardiovascular diseases.FEBS J. 2019 Aug;286(15):2980-2993. doi: 10.1111/febs.14836. Epub 2019 Apr 11.
11 Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
12 A Genetic Investigation of the Well-Being Spectrum.Behav Genet. 2019 May;49(3):286-297. doi: 10.1007/s10519-019-09951-0. Epub 2019 Feb 27.
13 Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress.Neuromuscul Disord. 2003 May;13(4):322-33. doi: 10.1016/s0960-8966(02)00284-5.
14 Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet.Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H424-H433. doi: 10.1152/ajpheart.00127.2019. Epub 2019 Jun 21.
15 Lack of association of polymorphisms in elastin with pseudoexfoliation syndrome and glaucoma.J Glaucoma. 2010 Sep;19(7):432-6. doi: 10.1097/IJG.0b013e3181c4b0fe.
16 Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome: a randomized controlled trial.BMC Pediatr. 2019 May 28;19(1):170. doi: 10.1186/s12887-019-1544-1.
17 Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure.Physiol Genomics. 2002 Jul 12;10(1):31-44. doi: 10.1152/physiolgenomics.00122.2001.
18 Inhibition of lysyl oxidase-like 1 (LOXL1) expression arrests liver fibrosis progression in cirrhosis by reducing elastin crosslinking.Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1129-1137. doi: 10.1016/j.bbadis.2018.01.019. Epub 2018 Jan 31.
19 Simultaneous Assessment of Cardiac Inflammation and Extracellular Matrix Remodeling after Myocardial Infarction.Circ Cardiovasc Imaging. 2018 Nov;11(11):e007453. doi: 10.1161/CIRCIMAGING.117.007453. Epub 2018 Nov 15.
20 Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.J Oral Pathol Med. 2020 Feb;49(2):150-155. doi: 10.1111/jop.12975. Epub 2019 Dec 1.
21 Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3/Cathepsin S Signaling Pathway.Int J Mol Sci. 2019 Aug 27;20(17):4202. doi: 10.3390/ijms20174202.
22 Reduction and fragmentation of elastic fibers in the skin of obese mice is associated with altered mRNA expression levels of fibrillin-1 and neprilysin.Connect Tissue Res. 2017 Sep;58(5):479-486. doi: 10.1080/03008207.2016.1255205. Epub 2016 Nov 28.
23 Impact of aging on inflammatory and immune responses during elastin peptide-induced murine emphysema.Am J Physiol Lung Cell Mol Physiol. 2019 Apr 1;316(4):L608-L620. doi: 10.1152/ajplung.00402.2018. Epub 2019 Jan 24.
24 A case of paraneoplastic elastosis perforans serpiginosa associated with ovarian malignancy.Int J Dermatol. 2018 Apr;57(4):470-472. doi: 10.1111/ijd.13854. Epub 2018 Jan 22.
25 Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes.BMC Med Genet. 2007 Jul 31;8:49. doi: 10.1186/1471-2350-8-49.
26 Association of polymorphisms in the elastin gene with sporadic ruptured intracranial aneurysms and unruptured intracranial aneurysms in Chinese patients.Int J Neurosci. 2013 Jul;123(7):454-8. doi: 10.3109/00207454.2013.763803. Epub 2013 Feb 6.
27 Ring sideroblasts in AML are associated with adverse risk characteristics and have a distinct gene expression pattern.Blood Adv. 2019 Oct 22;3(20):3111-3122. doi: 10.1182/bloodadvances.2019000518.
28 Elastin-Specific Autoimmunity in Smokers With Thoracic Aortic Aneurysm and Dissection is Independent of Chronic Obstructive Pulmonary Disease.J Am Heart Assoc. 2019 Apr 16;8(8):e011671. doi: 10.1161/JAHA.118.011671.
29 Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet. 2006 Mar;43(3):255-8. doi: 10.1136/jmg.2005.034157. Epub 2005 Aug 5.
30 Expression levels of cathepsin L and cystatin C in a hyperglycemic environment were associated with aortic aneurysm development in a mouse model.J Int Med Res. 2019 Jun;47(6):2499-2506. doi: 10.1177/0300060519847880. Epub 2019 May 17.
31 Spontaneous development and rupture of pulmonary artery aneurysm: a rare complication in an infant with peripheral pulmonary artery stenoses due to mutation of the elastin gene.Pediatr Cardiol. 2008 Mar;29(2):438-41. doi: 10.1007/s00246-007-9096-9. Epub 2007 Oct 3.
32 Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis.J Bone Miner Res. 2007 Feb;22(2):243-50. doi: 10.1359/jbmr.061102.
33 ELN gene triplication responsible for familial supravalvular aortic aneurysm.Cardiol Young. 2015 Apr;25(4):712-7. doi: 10.1017/S1047951114000766. Epub 2014 Jun 16.
34 Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin.Am J Med Genet. 1998 Jun 16;78(1):82-9. doi: 10.1002/(sici)1096-8628(19980616)78:1<82::aid-ajmg17>3.0.co;2-k.
35 Moyamoya disease and artery tortuosity as rare phenotypes in a patient with an elastin mutation.Am J Med Genet A. 2016 Jul;170(7):1924-7. doi: 10.1002/ajmg.a.37662. Epub 2016 Apr 15.
36 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.
37 Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis.Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L800-8. doi: 10.1152/ajplung.00176.2007. Epub 2007 Jul 6.
38 Microscopy with ultraviolet surface excitation (MUSE): A novel approach to real-time inexpensive slide-free dermatopathology.J Cutan Pathol. 2018 Jul;45(7):498-503. doi: 10.1111/cup.13255. Epub 2018 May 8.
39 Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?.Orphanet J Rare Dis. 2012 Sep 22;7:70. doi: 10.1186/1750-1172-7-70.
40 Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis.Respir Res. 2018 Mar 20;19(1):45. doi: 10.1186/s12931-018-0747-6.
41 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
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 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
44 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
45 Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Res. 2004 Jun 15;64(12):4218-26.
46 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
47 Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
48 The effects of a novel synthetic retinoid, seletinoid G, on the expression of extracellular matrix proteins in aged human skin in vivo. Clin Chim Acta. 2005 Dec;362(1-2):161-9. doi: 10.1016/j.cccn.2005.06.016. Epub 2005 Aug 1.
49 Collagen and elastin changes in D-penicillamine-induced pseudoxanthoma elasticum-like skin. Br J Dermatol. 1986 Mar;114(3):381-8. doi: 10.1111/j.1365-2133.1986.tb02832.x.
50 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.
51 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
52 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
53 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.