Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA53PGQ)

• DOT Name: Late cornified envelope protein 2B (LCE2B)
• Synonyms: Late envelope protein 10; Skin-specific protein Xp5; Small proline-rich-like epidermal differentiation complex protein 1B
• Gene Name: LCE2B
• Related Disease:
  Advanced cancer
  Prostate cancer
  Prostate neoplasm
  Xeroderma pigmentosum
• UniProt ID: LCE2B_HUMAN
• Pfam ID: PF14672
• Sequence:
  MSCQQNQQQCQPPPKCPPKCTPKCPPKCPPKCLPQCPAPCSPAVSSCCGPISGGCCGPSS
  GGCCNSGAGGCCLSHHRPRLFHRRRHQSPDCCESEPSGGSGCCHSSGGCC
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Late cornified envelope protein 2B (LCE2B).	[4]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Late cornified envelope protein 2B (LCE2B).	[4]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Late cornified envelope protein 2B (LCE2B).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Late cornified envelope protein 2B (LCE2B).	[7]
Manganese	DMKT129	Investigative	Manganese increases the expression of Late cornified envelope protein 2B (LCE2B).	[8]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Late cornified envelope protein 2B (LCE2B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Late cornified envelope protein 2B (LCE2B).	[6]

References

• [1] Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.Br J Dermatol. 2015 Apr;172(4):1096-102. doi: 10.1111/bjd.13429. Epub 2015 Feb 27.
• [2] Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.Nat Genet. 2018 May;50(5):682-692. doi: 10.1038/s41588-018-0086-z. Epub 2018 Apr 16.
• [3] Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients. J Dermatol. 2017 Jan;44(1):71-75. doi: 10.1111/1346-8138.13576. Epub 2016 Sep 8.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.