Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRVC5OD)

• DOT Name: Small proline-rich protein 4 (SPRR4)
• Gene Name: SPRR4
• UniProt ID: SPRR4_HUMAN
• Sequence:
  MSSQQQQRQQQQCPPQRAQQQQVKQPCQPPPVKCQETCAPKTKDPCAPQVKKQCPPKGTI
  IPAQQKCPSAQQASKSKQK
• Function: Cross-linked envelope protein of keratinocytes. Involved in UV-induced cornification.

Molecular Interaction Atlas (MIA) 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 Small proline-rich protein 4 (SPRR4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Small proline-rich protein 4 (SPRR4).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Small proline-rich protein 4 (SPRR4).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Small proline-rich protein 4 (SPRR4).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small proline-rich protein 4 (SPRR4).	[5]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.