General Information of Drug Off-Target (DOT) (ID: OTJ6GNUP)

DOT Name Endothelin-converting enzyme-like 1 (ECEL1)
Synonyms EC 3.4.24.-; Xce protein
Gene Name ECEL1
Related Disease
Distal arthrogryposis type 5D ( )
Advanced cancer ( )
Arthrogryposis ( )
Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome ( )
Centronuclear myopathy ( )
Congenital fibrosis of extraocular muscles ( )
Duane retraction syndrome ( )
Movement disorder ( )
Neuromuscular disease ( )
Ptosis ( )
Refractive error ( )
Distal arthrogryposis ( )
Neoplasm ( )
Neuroblastoma ( )
UniProt ID
ECEL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.4.24.-
Pfam ID
PF01431 ; PF05649
Sequence
MEPPYSLTAHYDEFQEVKYVSRCGAGGARGASLPPGFPLGAARSATGARSGLPRWNRREV
CLLSGLVFAAGLCAILAAMLALKYLGPVAAGGGACPEGCPERKAFARAARFLAANLDASI
DPCQDFYSFACGGWLRRHAIPDDKLTYGTIAAIGEQNEERLRRLLARPGGGPGGAAQRKV
RAFFRSCLDMREIERLGPRPMLEVIEDCGGWDLGGAEERPGVAARWDLNRLLYKAQGVYS
AAALFSLTVSLDDRNSSRYVIRIDQDGLTLPERTLYLAQDEDSEKILAAYRVFMERVLSL
LGADAVEQKAQEILQVEQQLANITVSEHDDLRRDVSSMYNKVTLGQLQKITPHLRWKWLL
DQIFQEDFSEEEEVVLLATDYMQQVSQLIRSTPHRVLHNYLVWRVVVVLSEHLSPPFREA
LHELAQEMEGSDKPQELARVCLGQANRHFGMALGALFVHEHFSAASKAKVQQLVEDIKYI
LGQRLEELDWMDAETRAAARAKLQYMMVMVGYPDFLLKPDAVDKEYEFEVHEKTYFKNIL
NSIRFSIQLSVKKIRQEVDKSTWLLPPQALNAYYLPNKNQMVFPAGILQPTLYDPDFPQS
LNYGGIGTIIGHELTHGYDDWGGQYDRSGNLLHWWTEASYSRFLRKAECIVRLYDNFTVY
NQRVNGKHTLGENIADMGGLKLAYHAYQKWVREHGPEHPLPRLKYTHDQLFFIAFAQNWC
IKRRSQSIYLQVLTDKHAPEHYRVLGSVSQFEEFGRAFHCPKDSPMNPAHKCSVW
Function May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.
Tissue Specificity
Highly expressed in the CNS, in particular in putamen, spinal cord, medulla and subthalamic nucleus. A strong signal was also detected in uterine subepithelial cells and around renal blood vessels. Detected at lower levels in amygdala, caudate, thalamus, pancreas and skeletal muscle. Detected at very low levels in substantia nigra, cerebellum, cortex, corpus callosum and hippocampus.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Distal arthrogryposis type 5D DISYDVKR Definitive Autosomal recessive [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Arthrogryposis DISC81CM Strong Genetic Variation [3]
Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome DISBCS1Y Strong Genetic Variation [4]
Centronuclear myopathy DISXBEJO Strong Genetic Variation [5]
Congenital fibrosis of extraocular muscles DISE84PU Strong Genetic Variation [6]
Duane retraction syndrome DISOEBK2 Strong Genetic Variation [6]
Movement disorder DISOJJ2D Strong Biomarker [4]
Neuromuscular disease DISQTIJZ Strong Biomarker [5]
Ptosis DISJZNIY Strong Genetic Variation [6]
Refractive error DISWNEQ1 Strong Genetic Variation [7]
Distal arthrogryposis DIS3QIEL moderate Genetic Variation [3]
Neoplasm DISZKGEW moderate Altered Expression [8]
Neuroblastoma DISVZBI4 moderate Altered Expression [8]
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⏷ Show the Full List of 14 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Endothelin-converting enzyme-like 1 (ECEL1). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Endothelin-converting enzyme-like 1 (ECEL1). [13]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Endothelin-converting enzyme-like 1 (ECEL1). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Endothelin-converting enzyme-like 1 (ECEL1). [11]
Folic acid DMEMBJC Approved Folic acid increases the expression of Endothelin-converting enzyme-like 1 (ECEL1). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Endothelin-converting enzyme-like 1 (ECEL1). [14]
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References

1 Mutations in ECEL1 cause distal arthrogryposis type 5D. Am J Hum Genet. 2013 Jan 10;92(1):150-6. doi: 10.1016/j.ajhg.2012.11.014. Epub 2012 Dec 20.
2 The health behaviour status of teenage and young adult cancer patients and survivors in the United Kingdom.Support Care Cancer. 2020 Feb;28(2):767-777. doi: 10.1007/s00520-019-04719-y. Epub 2019 May 29.
3 A novel ECEL1 mutation expands the phenotype of distal arthrogryposis multiplex congenita type 5D to include pretibial vertical skin creases.Am J Med Genet A. 2018 Jun;176(6):1405-1410. doi: 10.1002/ajmg.a.38691. Epub 2018 Apr 16.
4 New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis.Neurochem Res. 2019 Jun;44(6):1279-1288. doi: 10.1007/s11064-018-2665-x. Epub 2018 Oct 24.
5 ECEL1 mutation causes fetal arthrogryposis multiplex congenita.Am J Med Genet A. 2015 Apr;167A(4):731-43. doi: 10.1002/ajmg.a.37018. Epub 2015 Feb 23.
6 The ECEL1-related strabismus phenotype is consistent with congenital cranial dysinnervation disorder.J AAPOS. 2014 Aug;18(4):362-7. doi: 10.1016/j.jaapos.2014.03.005.
7 Expanding the phenotypic spectrum of ECEL1-related congenital contracture syndromes.Clin Genet. 2014 Jun;85(6):562-7. doi: 10.1111/cge.12224. Epub 2013 Jul 19.
8 High expression of the novel endothelin-converting enzyme genes, Nbla03145/ECEL1alpha and beta, is associated with favorable prognosis in human neuroblastomas.Int J Oncol. 2003 Apr;22(4):815-22.
9 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.
10 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
11 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
12 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
13 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.
14 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.