Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47THNK)

• DOT Name: Small proline-rich protein 2D (SPRR2D)
• Synonyms: SPR-2D; Small proline-rich protein II; SPR-II
• Gene Name: SPRR2D
• UniProt ID: SPR2D_HUMAN
• Pfam ID: PF14820
• Sequence:
  MSYQQQQCKQPCQPPPVCPTPKCPEPCPPPKCPEPCPSPKCPQPCPPQQCQQKYPPVTPS
  PPCQPKCPPKSK
• Function: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Small proline-rich protein 2D (SPRR2D).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small proline-rich protein 2D (SPRR2D).	[2]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Small proline-rich protein 2D (SPRR2D).	[3]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Small proline-rich protein 2D (SPRR2D).	[4]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Small proline-rich protein 2D (SPRR2D).	[1]

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 Small proline-rich protein 2D (SPRR2D).	[5]

References

• [1] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [4] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [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.