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

DOT Name Envoplakin (EVPL)
Synonyms 210 kDa cornified envelope precursor protein; 210 kDa paraneoplastic pemphigus antigen; p210
Gene Name EVPL
Related Disease
Squamous cell carcinoma ( )
Abetalipoproteinemia ( )
Acute leukaemia ( )
Acute megakaryoblastic leukemia ( )
Acute monocytic leukemia ( )
Acute myelomonocytic leukemia M4 ( )
Advanced cancer ( )
Arteriosclerosis ( )
Atherosclerosis ( )
B-cell acute lymphoblastic leukaemia ( )
Childhood acute lymphoblastic leukemia ( )
Childhood acute megakaryoblastic leukemia ( )
Childhood myelodysplastic syndrome ( )
Chronic myelogenous leukaemia ( )
Chronic myelomonocytic leukaemia ( )
Esophageal cancer ( )
Leukemia ( )
Lymphoid leukemia ( )
Myelodysplastic syndrome ( )
Myeloid leukaemia ( )
Neoplasm ( )
Retinoblastoma ( )
Systemic lupus erythematosus ( )
Vibrio cholerae infection ( )
Acute myelogenous leukaemia ( )
Essential thrombocythemia ( )
leukaemia ( )
Carcinoma of esophagus ( )
Chromosomal disorder ( )
Glycogen storage disease VI ( )
Neoplasm of esophagus ( )
Thyroid gland follicular carcinoma ( )
Tourette syndrome ( )
UniProt ID
EVPL_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4QMD
Pfam ID
PF00681 ; PF17902 ; PF21020
Sequence
MFKGLSKGSQGKGSPKGSPAKGSPKGSPSRHSRAATQELALLISRMQANADQVERDILET
QKRLQQDRLNSEQSQALQHQQETGRSLKEAEVLLKDLFLDVDKARRLKHPQAEEIEKDIK
QLHERVTQECAEYRALYEKMVLPPDVGPRVDWARVLEQKQKQVCAGQYGPGMAELEQQIA
EHNILQKEIDAYGQQLRSLVGPDAATIRSQYRDLLKAASWRGQSLGSLYTHLQGCTRQLS
ALAEQQRRILQQDWSDLMADPAGVRREYEHFKQHELLSQEQSVNQLEDDGERMVELRHPA
VGPIQAHQEALKMEWQNFLNLCICQETQLQHVEDYRRFQEEADSVSQTLAKLNSNLDAKY
SPAPGGPPGAPTELLQQLEAEEKRLAVTERATGDLQRRSRDVAPLPQRRNPPQQPLHVDS
ICDWDSGEVQLLQGERYKLVDNTDPHAWVVQGPGGETKRAPAACFCIPAPDPDAVARASR
LASELQALKQKLATVQSRLKASAVESLRPSQQAPSGSDLANPQAQKLLTQMTRLDGDLGQ
IERQVLAWARAPLSRPTPLEDLEGRIHSHEGTAQRLQSLGTEKETAQKECEAFLSTRPVG
PAALQLPVALNSVKNKFSDVQVLCSLYGEKAKAALDLERQIQDADRVIRGFEATLVQEAP
IPAEPGALQERVSELQRQRRELLEQQTCVLRLHRALKASEHACAALQNNFQEFCQDLPRQ
QRQVRALTDRYHAVGDQLDLREKVVQDAALTYQQFKNCKDNLSSWLEHLPRSQVRPSDGP
SQIAYKLQAQKRLTQEIQSRERDRATASHLSQALQAALQDYELQADTYRCSLEPTLAVSA
PKRPRVAPLQESIQAQEKNLAKAYTEVAAAQQQLLQQLEFARKMLEKKELSEDIRRTHDA
KQGSESPAQAGRESEALKAQLEEERKRVARVQHELEAQRSQLLQLRTQRPLERLEEKEVV
EFYRDPQLEGSLSRVKAQVEEEGKRRAGLQADLEVAAQKVVQLESKRKTMQPHLLTKEVT
QVERDPGLDSQAAQLRIQIQQLRGEDAVISARLEGLKKELLALEKREVDVKEKVVVKEVV
KVEKNLEMVKAAQALRLQMEEDAARRKQAEEAVAKLQARIEDLERAISSVEPKVIVKEVK
KVEQDPGLLQESSRLRSLLEEERTKNATLARELSDLHSKYSVVEKQRPKVQLQERVHEIF
QVDPETEQEITRLKAKLQEMAGKRSGVEKEVEKLLPDLEVLRAQKPTVEYKEVTQEVVRH
ERSPEVLREIDRLKAQLNELVNSHGRSQEQLIRLQGERDEWRRERAKVETKTVSKEVVRH
EKDPVLEKEAERLRQEVREAAQKRRAAEDAVYELQSKRLLLERRKPEEKVVVQEVVVTQK
DPKLREEHSRLSGSLDEEVGRRRQLELEVQQLRAGVEEQEGLLSFQEDRSKKLAVERELR
QLTLRIQELEKRPPTVQEKIIMEEVVKLEKDPDLEKSTEALRWDLDQEKTQVTELNRECK
NLQVQIDVLQKAKSQEKTIYKEVIRVQKDRVLEDERARVWEMLNRERTARQAREEEARRL
RERIDRAETLGRTWSREESELQRARDQADQECGRLQQELRALERQKQQQTLQLQEESKLL
SQKTESERQKAAQRGQELSRLEAAILREKDQIYEKERTLRDLHAKVSREELSQETQTRET
NLSTKISILEPETGKDMSPYEAYKRGIIDRGQYLQLQELECDWEEVTTSGPCGEESVLLD
RKSGKQYSIEAALRCRRISKEEYHLYKDGHLPISEFALLVAGETKPSSSLSIGSIISKSP
LASPAPQSTSFFSPSFSLGLGDDSFPIAGIYDTTTDNKCSIKTAVAKNMLDPITGQKLLE
AQAATGGIVDLLSRERYSVHKAMERGLIENTSTQRLLNAQKAFTGIEDPVTKKRLSVGEA
VQKGWMPRESVLPHLQVQHLTGGLIDPKRTGRIPIQQALLSGMISEELAQLLQDESSYEK
DLTDPISKERLSYKEAMGRCRKDPLSGLLLLPAALEGYRCYRSASPTVPRSLR
Function Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments.
Tissue Specificity Exclusively expressed in stratified squamous epithelia.
Reactome Pathway
Formation of the cornified envelope (R-HSA-6809371 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Squamous cell carcinoma DISQVIFL Definitive Genetic Variation [1]
Abetalipoproteinemia DISMSS7T Strong Biomarker [2]
Acute leukaemia DISDQFDI Strong Altered Expression [3]
Acute megakaryoblastic leukemia DIS0JX3M Strong Genetic Variation [4]
Acute monocytic leukemia DIS28NEL Strong Genetic Variation [5]
Acute myelomonocytic leukemia M4 DISRRMV2 Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Biomarker [7]
Arteriosclerosis DISK5QGC Strong Biomarker [8]
Atherosclerosis DISMN9J3 Strong Biomarker [8]
B-cell acute lymphoblastic leukaemia DISKLOKC Strong Biomarker [9]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Posttranslational Modification [10]
Childhood acute megakaryoblastic leukemia DIS5VZDR Strong Genetic Variation [4]
Childhood myelodysplastic syndrome DISMN80I Strong Biomarker [11]
Chronic myelogenous leukaemia DIS0301E Strong Genetic Variation [12]
Chronic myelomonocytic leukaemia DISDN5P7 Strong Altered Expression [13]
Esophageal cancer DISGB2VN Strong Genetic Variation [1]
Leukemia DISNAKFL Strong Biomarker [14]
Lymphoid leukemia DIS65TYQ Strong Posttranslational Modification [10]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [11]
Myeloid leukaemia DISMN944 Strong Altered Expression [15]
Neoplasm DISZKGEW Strong Biomarker [16]
Retinoblastoma DISVPNPB Strong Biomarker [17]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [18]
Vibrio cholerae infection DISW7E3U Strong Biomarker [8]
Acute myelogenous leukaemia DISCSPTN moderate Biomarker [19]
Essential thrombocythemia DISWWK11 moderate Genetic Variation [20]
leukaemia DISS7D1V moderate Biomarker [14]
Carcinoma of esophagus DISS6G4D Limited Biomarker [21]
Chromosomal disorder DISM5BB5 Limited Biomarker [22]
Glycogen storage disease VI DIS46FMA Limited Altered Expression [23]
Neoplasm of esophagus DISOLKAQ Limited Biomarker [21]
Thyroid gland follicular carcinoma DISFK2QT Limited Genetic Variation [24]
Tourette syndrome DISX9D54 No Known Unknown [25]
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⏷ Show the Full List of 33 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
Arsenic trioxide DM61TA4 Approved Envoplakin (EVPL) decreases the response to substance of Arsenic trioxide. [31]
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2 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 Envoplakin (EVPL). [26]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Envoplakin (EVPL). [29]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Envoplakin (EVPL). [27]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Envoplakin (EVPL). [30]
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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 Envoplakin (EVPL). [28]
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References

1 Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.Oncol Rep. 2005 Apr;13(4):703-7.
2 p210(Bcr-Abl) desensitizes Cdc42 GTPase signaling for SDF-1alpha-directed migration in chronic myeloid leukemia cells.Oncogene. 2009 Nov 19;28(46):4105-15. doi: 10.1038/onc.2009.260. Epub 2009 Aug 31.
3 Acute leukemias expressing p210-and p 190-type bcr/abl mRNAs: report of two cases and review of the literature.Acta Haematol. 1996;96(2):99-104. doi: 10.1159/000203724.
4 De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome.J Hematol Oncol. 2011 Nov 10;4:45. doi: 10.1186/1756-8722-4-45.
5 Establishment of a novel human myeloid leukaemia cell line (HNT-34) with t(3;3)(q21;q26), t(9;22)(q34;q11) and the expression of EVI1 gene, P210 and P190 BCR/ABL chimaeric transcripts from a patient with AML after MDS with 3q21q26 syndrome.Br J Haematol. 1997 Aug;98(2):399-407. doi: 10.1046/j.1365-2141.1997.2143029.x.
6 p210 BCR/ABL1 as a secondary change in a patient with acute myelomonocytic leukemia (M4Eo) with inv(16).Int J Hematol. 2012 Dec;96(6):814-7. doi: 10.1007/s12185-012-1190-y. Epub 2012 Oct 11.
7 Characterization of the CDR3 structure of the V21 T cell clone in patients with P210(BCR-ABL)-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia.Hum Immunol. 2011 Oct;72(10):798-804. doi: 10.1016/j.humimm.2011.06.015. Epub 2011 Jul 20.
8 B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice.Vascul Pharmacol. 2018 Dec;111:54-61. doi: 10.1016/j.vph.2018.09.002. Epub 2018 Sep 19.
9 Pre-B acute lymphoblastic leukemia with b3a2 (p210) and e1a2 (p190) BCR-ABL fusion transcripts relapsing as chronic myelogenous leukemia with a less differentiated b3a2 (p210) clone.Leukemia. 1999 Dec;13(12):2007-11. doi: 10.1038/sj.leu.2401598.
10 Pak1 gene functioned differentially in different BCR-ABL subtypes in leukemiagenesis and treatment response through STAT5 pathway.Leuk Res. 2019 Apr;79:6-16. doi: 10.1016/j.leukres.2019.01.012. Epub 2019 Jan 24.
11 Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage.Br J Haematol. 1994 May;87(1):51-6. doi: 10.1111/j.1365-2141.1994.tb04869.x.
12 Effective Concentration of a Multikinase Inhibitor within Bone Marrow Correlates with In Vitro Cell Killing in Therapy-Resistant Chronic Myeloid Leukemia.Mol Cancer Ther. 2016 May;15(5):899-910. doi: 10.1158/1535-7163.MCT-15-0577-T. Epub 2016 Feb 4.
13 Childhood chronic myeloid leukemia with monocytosis.Indian J Pediatr. 2010 Oct;77(10):1143-5. doi: 10.1007/s12098-010-0200-4. Epub 2010 Sep 30.
14 Disparate effects of Shb gene deficiency on disease characteristics in murine models of myeloid, B-cell, and T-cell leukemia.Tumour Biol. 2018 Apr;40(4):1010428318771472. doi: 10.1177/1010428318771472.
15 Leukemia patient-derived lymphoblastoid cell lines exhibit increased induction of leukemia-associated transcripts following high-dose irradiation.Exp Hematol. 1999 Sep;27(9):1397-401. doi: 10.1016/s0301-472x(99)00082-x.
16 Droplet digital PCR for BCR/ABL(P210) detection of chronic myeloid leukemia: A high sensitive method of the minimal residual disease and disease progression.Eur J Haematol. 2018 Sep;101(3):291-296. doi: 10.1111/ejh.13084. Epub 2018 Jul 12.
17 The presence of the Rb c-box peptide in the cytoplasm inhibits p210bcr-abl transforming function.Oncogene. 1999 Feb 25;18(8):1589-95. doi: 10.1038/sj.onc.1202479.
18 RETRACTED: Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K.Exp Cell Res. 2018 Apr 1;365(1):138-144. doi: 10.1016/j.yexcr.2018.02.034. Epub 2018 Mar 6.
19 Coexistence of p210(BCR-ABL) and CBF-MYH11 fusion genes in myeloid leukemia: A report of 4 cases.Oncol Lett. 2017 Nov;14(5):5171-5178. doi: 10.3892/ol.2017.6812. Epub 2017 Aug 24.
20 Concomitant presence of JAK2V617F mutation and BCRABL translocation in two patients: A new entity or a variant of myeloproliferative neoplasms (Case report).Mol Med Rep. 2018 Jul;18(1):1001-1006. doi: 10.3892/mmr.2018.9032. Epub 2018 May 17.
21 Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): the integration of genetic and physical maps of the TOC region on 17q25.Genomics. 1999 Jul 15;59(2):234-42. doi: 10.1006/geno.1999.5857.
22 Acquired loss of p53 induces blastic transformation in p210(bcr/abl)-expressing hematopoietic cells: a transgenic study for blast crisis of human CML.Blood. 2000 Feb 15;95(4):1144-50.
23 A Philadelphia chromosome positive acute lymphoblastic leukemia of donor origin after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase.Bone Marrow Transplant. 2000 Jun;25(11):1209-11. doi: 10.1038/sj.bmt.1702418.
24 Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.Carcinogenesis. 2016 Jul;37(7):677-684. doi: 10.1093/carcin/bgw047. Epub 2016 Apr 28.
25 De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
26 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.
27 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
28 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.
29 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.
30 Unique bisphenol A transcriptome in prostate cancer: novel effects on ERbeta expression that correspond to androgen receptor mutation status. Environ Health Perspect. 2007 Nov;115(11):1646-53. doi: 10.1289/ehp.10283.
31 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.