Details of Drug Off-Target (DOT)

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

• DOT Name: Enolase-phosphatase E1 (ENOPH1)
• Synonyms: EC 3.1.3.77; 2,3-diketo-5-methylthio-1-phosphopentane phosphatase; MASA homolog
• Gene Name: ENOPH1
• Related Disease:
  Intellectual disability
  Chikungunya virus infection
  Corpus callosum, agenesis of
  Glioma
  Malignant glioma
  X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
  Hepatocellular carcinoma
  Hydrocephalus
  MASA syndrome
• UniProt ID: ENOPH_HUMAN
• PDB ID: 1YNS; 1ZS9
• EC Number: 3.1.3.77
• Pfam ID: PF00702
• Sequence:
  MVVLSVPAEVTVILLDIEGTTTPIAFVKDILFPYIEENVKEYLQTHWEEEECQQDVSLLR
  KQAEEDAHLDGAVPIPAASGNGVDDLQQMIQAVVDNVCWQMSLDRKTTALKQLQGHMWRA
  AFTAGRMKAEFFADVVPAVRKWREAGMKVYIYSSGSVEAQKLLFGHSTEGDILELVDGHF
  DTKIGHKVESESYRKIADSIGCSTNNILFLTDVTREASAAEEADVHVAVVVRPGNAGLTD
  DEKTYYSLITSFSELYLPSST
• Function: Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene).
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Methionine salvage pathway (R-HSA-1237112)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[2]
Corpus callosum, agenesis of	DISO9P40	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[4]
Malignant glioma	DISFXKOV	Strong	Biomarker	[4]
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius	DIS6QXIR	moderate	Genetic Variation	[5]
Hepatocellular carcinoma	DIS0J828	Disputed	Altered Expression	[6]
Hydrocephalus	DISIZUF7	Limited	Genetic Variation	[7]
MASA syndrome	DISEFI9B	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Enolase-phosphatase E1 (ENOPH1) affects the response to substance of Topotecan.	[16]

6 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 Enolase-phosphatase E1 (ENOPH1).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Enolase-phosphatase E1 (ENOPH1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Enolase-phosphatase E1 (ENOPH1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Enolase-phosphatase E1 (ENOPH1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Enolase-phosphatase E1 (ENOPH1).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Enolase-phosphatase E1 (ENOPH1).	[15]

2 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 affects the methylation of Enolase-phosphatase E1 (ENOPH1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Enolase-phosphatase E1 (ENOPH1).	[14]

References

• [1] Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.Hum Mutat. 1998;12(4):259-66. doi: 10.1002/(SICI)1098-1004(1998)12:4<259::AID-HUMU7>3.0.CO;2-A.
• [2] Proteomics profiling of chikungunya-infected Aedes albopictus C6/36 cells reveal important mosquito cell factors in virus replication.PLoS Negl Trop Dis. 2015 Mar 4;9(3):e0003544. doi: 10.1371/journal.pntd.0003544. eCollection 2015 Mar.
• [3] Prenatal diagnosis in a family with X-linked hydrocephalus.Prenat Diagn. 2005 Oct;25(10):930-3. doi: 10.1002/pd.1228.
• [4] Enolase-phosphatase 1 as a novel potential malignant glioma indicator promotes cell proliferation and migration.Oncol Rep. 2018 Oct;40(4):2233-2241. doi: 10.3892/or.2018.6592. Epub 2018 Jul 24.
• [5] Multiple exon screening using restriction endonuclease fingerprinting (REF): detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.Hum Mutat. 1998;11(3):222-30. doi: 10.1002/(SICI)1098-1004(1998)11:3<222::AID-HUMU7>3.0.CO;2-J.
• [6] Integration of metabolomics and expression of enolase-phosphatase 1 links to hepatocellular carcinoma progression.Theranostics. 2019 May 26;9(12):3639-3652. doi: 10.7150/thno.31693. eCollection 2019.
• [7] A novel L1CAM mutation with L1 spectrum disorders.Prenat Diagn. 2005 Jan;25(1):57-9. doi: 10.1002/pd.978.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [13] 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.
• [14] 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.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.