Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU49OK5)

• DOT Name: Protein enabled homolog (ENAH)
• Gene Name: ENAH
• UniProt ID: ENAH_HUMAN
• PDB ID: 2HO2; 2IYB; 2XQN; 4MY6; 5N91; 5N9C; 5N9P; 5NAJ; 5NBF; 5NBX; 5NC2; 5NC7; 5NCF; 5NCG; 5NCP; 5ND0; 5NDU; 5NEG; 6RCF; 6RCJ; 6RD2; 6XVT; 6XXR; 7A5M; 7AKI; 7LXE
• Pfam ID: PF08776 ; PF00568
• Sequence:
  MSEQSICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVI
  NCAIPKGLKYNQATQTFHQWRDARQVYGLNFGSKEDANVFASAMMHALEVLNSQETGPTL
  PRQNSQLPAQVQNGPSQEELEIQRRQLQEQQRQKELERERLERERMERERLERERLERER
  LERERLEQEQLERERQERERQERLERQERLERQERLERQERLDRERQERQERERLERLER
  ERQERERQEQLEREQLEWERERRISSAAAPASVETPLNSVLGDSSASEPGLQAASQPAET
  PSQQGIVLGPLAPPPPPPLPPGPAQASVALPPPPGPPPPPPLPSTGPPPPPPPPPLPNQV
  PPPPPPPPAPPLPASGFFLASMSEDNRPLTGLAAAIAGAKLRKVSRMEDTSFPSGGNAIG
  VNSASSKTDTGRGNGPLPLGGSGLMEEMSALLARRRRIAEKGSTIETEQKEDKGEDSEPV
  TSKASSTSTPEPTRKPWERTNTMNGSKSPVISRRDSPRKNQIVFDNRSYDSLHRPKSTPL
  SQPSANGVQTEGLDYDRLKQDILDEMRKELTKLKEELIDAIRQELSKSNTA
• Function: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation.
• Tissue Specificity: Expressed in myoepithelia of parotid, breast, bronchial glands and sweat glands. Expressed in colon-rectum muscolaris mucosae epithelium, pancreas acinar ductal epithelium, endometrium epithelium, prostate fibromuscolar stroma and placenta vascular media. Overexpressed in a majority of breast cancer cell lines and primary breast tumor lesions.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Axon guidance (hsa04360)
  Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway:
  Signaling by ROBO receptors (R-HSA-376176)
  Generation of second messenger molecules (R-HSA-202433)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Protein enabled homolog (ENAH) affects the response to substance of Fluorouracil.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein enabled homolog (ENAH).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein enabled homolog (ENAH).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein enabled homolog (ENAH).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein enabled homolog (ENAH).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein enabled homolog (ENAH).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein enabled homolog (ENAH).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein enabled homolog (ENAH).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein enabled homolog (ENAH).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein enabled homolog (ENAH).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein enabled homolog (ENAH).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein enabled homolog (ENAH).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein enabled homolog (ENAH).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein enabled homolog (ENAH).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein enabled homolog (ENAH).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [14] Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 2012 Sep 15;21(18):4104-14. doi: 10.1093/hmg/dds239. Epub 2012 Jun 20.
• [15] 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.