Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG0VXM2)

• DOT Name: Late cornified envelope protein 1E (LCE1E)
• Synonyms: Late envelope protein 5
• Gene Name: LCE1E
• Related Disease: Familial multiple trichoepithelioma
• UniProt ID: LCE1E_HUMAN
• Pfam ID: PF14672
• Sequence:
  MSCQQSQQQCQPPPKCTPKCPPKCPTPKCPPKCPPKCPPVSSCCSVSSGGCCGSSSGGSC
  GSSSGGCCSSGGGGCCLSHHRHHRSHRHRPQSSDCCSQPSGGSSCCGGGSGQHSGGCC
• Function: Precursors of the cornified envelope of the stratum corneum.
• Tissue Specificity: Skin-specific. Expression was readily detected in adult trunk skin, adult arm skin, fetal skin, penal skin, vulva, esophagus and tongue. Not expressed in the cervix, rectum, lung, colon, or placenta.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial multiple trichoepithelioma	DISKZAUY	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Late cornified envelope protein 1E (LCE1E).	[2]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Late cornified envelope protein 1E (LCE1E).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Late cornified envelope protein 1E (LCE1E).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Late cornified envelope protein 1E (LCE1E).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Late cornified envelope protein 1E (LCE1E).	[7]

1 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 increases the methylation of Late cornified envelope protein 1E (LCE1E).	[5]

References

• [1] Single nucleotide polymorphisms in obesity-related genes and the risk of esophageal cancers.Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):1007-12. doi: 10.1158/1055-9965.EPI-08-0023.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation. J Dermatol Sci. 2014 Nov;76(2):112-9. doi: 10.1016/j.jdermsci.2014.08.003. Epub 2014 Aug 26.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.