Details of Drug Off-Target (DOT)

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

DOT Name	Late cornified envelope protein 3A (LCE3A)
Synonyms	Late envelope protein 13
Gene Name	LCE3A
Related Disease	Psoriasis ( ) Psoriatic arthritis ( )
UniProt ID	LCE3A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF14672
Sequence	MSCQQNQQQCQPPPKCPAKSPAQCLPPASSSCAPSSGGCGPSSERSCCLSHHRCRRSHRC RCQSSNSCDRGSGQQGGSSSCGHSSAGCC
Function	A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense (Probable). Possesses defensin-like antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, both aerobic and anaerobic species. Upon inflammation, may regulate skin barrier repair by shaping cutaneous microbiota composition and immune response to bacterial antigens.
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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Psoriasis	DIS59VMN	Strong	Altered Expression	[1]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[2]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Late cornified envelope protein 3A (LCE3A).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Late cornified envelope protein 3A (LCE3A).	[5]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Late cornified envelope protein 3A (LCE3A).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Late cornified envelope protein 3A (LCE3A).	[6]
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References

1	Pushing the Envelope in Psoriasis: Late Cornified Envelope Proteins Possess Antimicrobial Activity.J Invest Dermatol. 2017 Nov;137(11):2257-2259. doi: 10.1016/j.jid.2017.08.026.
2	Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.Am J Hum Genet. 2015 Dec 3;97(6):816-36. doi: 10.1016/j.ajhg.2015.10.019. Epub 2015 Nov 28.
3	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
4	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
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	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.