Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0EFCPB)

• DOT Name: Echinoderm microtubule-associated protein-like 5 (EML5)
• Synonyms: EMAP-5
• Gene Name: EML5
• Related Disease:
  Bronchopulmonary dysplasia
  Carcinoma
  Pancreatic cancer
  Schizophrenia
  Neoplasm
• UniProt ID: EMAL5_HUMAN
• Pfam ID: PF12894 ; PF03451 ; PF00400
• Sequence:
  MAARSAPSCHLRLEWVYGYRGHQCRNNLYYTAAKEIVYFVAGVGVVYSPREHRQKFYRGH
  SDDIISLALHPERVLVATGQVGKEPYICIWDSYTVQTISVLKDVHTHGIACLAFDLDGQR
  LVSVGLDSKNAVCVWDWKRGKMLSMAPGHTDRIFDISWDLYQPNKLVSCGVKHIKFWSLC
  GNALTPKRGVFGKTGDLQTILCLACARDELTYSGALNGDIYVWKGINLIRTIQGAHAAGI
  FSMNACEEGFATGGRDGCIRLWDLTFKPITVIDLRETDQGYKGLSVRSVCWRGDHILVGT
  QDSEIFEIVVQERNKPFLIMQGHCEGELWALAVHPTKPLAVTGSDDRSVRIWSLVDHALI
  ARCNMEEPIRCAAVNADGIHLALGMKDGSFTVLRVRDMTEVVHIKDRKEAIHELKYSPDG
  TYLAVGCNDSSVDIYGVAQRYKKVGECLGSLSFITHLDWSSDSRYLQTNDGNGKRLFYRM
  PGGKEVTSTEEIKGVHWASWTCVSGLEVNGIWPKYSDINDINSVDGNYIGQVLVTADDYG
  IIKLFRYPCLRKGAKFRKYIGHSAHVTNVRWSHDYQWVISIGGADHSVFQWKFIPERKLK
  DAVHIAPQESLADSHSDESDSDLSDVPELDSEIEQETQLTYRRQVYKEDLPQLKEQCKEK
  QKSATSKRRERAPGNSIRLHFVHGYRGYDCRSNLFYTQIGEIVYHVAAVGVIYNRQQNTQ
  RFYLGHDDDILCLTIHPLKDYVATGQVGRDPSIHIWDTETIKPLSILKGHHQYGVSAVDF
  SADGKRLASVGIDDSHTVVLWDWKKGEKLSIARGSKDKIFVVKMNPYVPDKLITAGIKHM
  KFWRKAGGGLIGRKGYIGTLGKNDTMMCAVYGWTEEMAFSGTSTGDVCIWRDIFLVKTVK
  AHDGPVFSMHALEKGFVTGGKDGIVALWDDSFERCLKTYAIKRAALAPGSKGLLLEDNPS
  IRAISLGHGHILVGTKNGEILEVDKSGPITLLVQGHMEGEVWGLATHPYLPICATVSDDK
  TLRIWDLSPSHCMLAVRKLKKGGRCCCFSPDGKALAVGLNDGSFLMANADTLEDLVSFHH
  RKDMISDIRFSPGSGKYLAVASHDSFIDIYNVMSSKRVGICKGATSYITHIDWDIRGKLL
  QVNTGAKEQLFFEAPRGKKQTIPSVEVEKIAWASWTSVLGLCCEGIWPVIGEVTDVTASC
  LTSDKMVLATGDDLGFVKLFRYPTKGKFGKFKRYVAHSTHVTNVRWTYDDSMLVTLGGTD
  MSLMVWTNEMEGYREKRPCDSEESDIDSEEDGGYDSDVTRENEISYTIRALSTNIRPMLG
  IKPHLQQKEPSIDERPPVSRAPPQPEKLQTNNVGKKKRPIEDLVLELIFGYRGRDCRNNV
  HYLNDGDDIIYHTASVGILHNVATGSQSFYQEHNDDILCLTVNQHPKFINIVATGQVGDS
  ADMSATAPSIHIWDAMNKQTLSILRCYHSKGVCSVSFSATGKLLLSVGLDPEHTITIWRW
  QEGAKIASRAGHNQRIFVAEFRPDSDTQFVSVGVKHVKFWTLAGRALLSKKGLLSTLEDA
  RMQTMLAIAFGANNLTFTGTISGDVCVWKDHILCRIVARAHNGPVFAMYTTLRDGLIVTG
  GKERPSKEGGAVKLWDQELRRCRAFRLETGQATDCVRSVCRGKGKILVGTRNAEIIEVGE
  KNAACNILVNGHVDGPIWGLATHPSRDFFLSAAEDGTVRLWDIADKKMLNKVNLGHAART
  VCYSPEGDMVAIGMKNGEFIILLVSSLKIWGKKRDRRCAIHDIRFSPDSRYLAVGSSENS
  VDFYDLTLGPTLNRISYCKDIPSFVIQMDFSADSSYLQVSSGCYKRHVYEVPSGKHLMDH
  AAIDRITWATWTSILGDEVLGIWSRHAEKADVNCACVSHSGISLVTGDDFGMVKLFDFPC
  PEKFAKHKRFLGHSPHVTNIRFTSGDRHVVSAGGDDCSLFVWKCVHTPH
• Function: May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[5]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[9]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[10]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Echinoderm microtubule-associated protein-like 5 (EML5).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Echinoderm microtubule-associated protein-like 5 (EML5).	[13]

References

• [1] Potential role for antiangiogenic proteins in the evolution of bronchopulmonary dysplasia.Antioxid Redox Signal. 2004 Feb;6(1):137-45. doi: 10.1089/152308604771978444.
• [2] Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.J Exp Med. 1999 Aug 2;190(3):341-54. doi: 10.1084/jem.190.3.341.
• [3] Enhancing cytotoxic agent activity in experimental pancreatic cancer through EMAP II combination therapy.Cancer Chemother Pharmacol. 2011 Sep;68(3):571-82. doi: 10.1007/s00280-010-1514-7. Epub 2010 Nov 26.
• [4] Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.Schizophr Res. 2011 Sep;131(1-3):43-51. doi: 10.1016/j.schres.2011.06.023. Epub 2011 Jul 14.
• [5] Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis.Microvasc Res. 2000 Jul;60(1):70-80. doi: 10.1006/mvre.2000.2249.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.