Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3EG75W)

• DOT Name: Epigen (EPGN)
• Synonyms: Epithelial mitogen; EPG
• Gene Name: EPGN
• Related Disease:
  Advanced cancer
  Alpha thalassemia
  Chagas disease
  Demyelinating polyneuropathy
  Neuromuscular disease
  Peripheral neuropathy
  Seborrhoeic dermatitis
  Vici syndrome
  Pulmonary disease
  Gastric cancer
  Stomach cancer
• UniProt ID: EPGN_HUMAN
• PDB ID: 5WB8
• Sequence:
  MALGVPISVYLLFNAMTALTEEAAVTVTPPITAQQGNWTVNKTEADNIEGPIALKFSHLC
  LEDHNSYCINGACAFHHELEKAICRCFTGYTGERCEHLTLTSYAVDSYEKYIAIGIGVGL
  LLSGFLVIFYCYIRKRCLKLKSPYNVCSGERRPL
• Function: Promotes the growth of epithelial cells. May stimulate the phosphorylation of EGFR and mitogen-activated protein kinases.
• Reactome Pathway:
  Signaling by EGFR (R-HSA-177929)
  GRB2 events in EGFR signaling (R-HSA-179812)
  GAB1 signalosome (R-HSA-180292)
  SHC1 events in EGFR signaling (R-HSA-180336)
  EGFR downregulation (R-HSA-182971)
  EGFR interacts with phospholipase C-gamma (R-HSA-212718)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alpha thalassemia	DIS5XGK0	Strong	Biomarker	[2]
Chagas disease	DIS8KNVF	Strong	Biomarker	[3]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Biomarker	[4]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[5]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[4]
Seborrhoeic dermatitis	DISNWVJU	Strong	Altered Expression	[6]
Vici syndrome	DISSUIIM	Strong	Genetic Variation	[5]
Pulmonary disease	DIS6060I	moderate	Biomarker	[7]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[8]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epigen (EPGN).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Epigen (EPGN).	[10]

References

• [1] Ectodomain shedding of the EGF-receptor ligand epigen is mediated by ADAM17.FEBS Lett. 2007 Jan 9;581(1):41-4. doi: 10.1016/j.febslet.2006.11.074. Epub 2006 Dec 6.
• [2] Diagnosis of alpha thalassemia in the newborn. Cord blood survey utilizing gene mapping.Pathology. 1984 Jan;16(1):16-21. doi: 10.3109/00313028409067905.
• [3] Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging.PLoS Negl Trop Dis. 2016 May 16;10(5):e0004724. doi: 10.1371/journal.pntd.0004724. eCollection 2016 May.
• [4] Increased activation of the epidermal growth factor receptor in transgenic mice overexpressing epigen causes peripheral neuropathy.Biochim Biophys Acta. 2013 Dec;1832(12):2068-76. doi: 10.1016/j.bbadis.2013.07.011. Epub 2013 Jul 27.
• [5] Vici syndrome: a review.Orphanet J Rare Dis. 2016 Feb 29;11:21. doi: 10.1186/s13023-016-0399-x.
• [6] Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice.EMBO Mol Med. 2014 Apr;6(4):442-57. doi: 10.1002/emmm.201303281. Epub 2014 Feb 6.
• [7] Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles. BMC Genomics. 2018 Apr 27;19(1):302.
• [8] Transcript level of AKR1C3 is down-regulated in gastric cancer. Biochem Cell Biol. 2016 Apr;94(2):138-46.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.