Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVKSA48)

• DOT Name: Shadow of prion protein (SPRN)
• Synonyms: Protein shadoo
• Gene Name: SPRN
• Related Disease:
  Creutzfeldt Jacob disease
  Prion disease
  Squamous cell carcinoma
• UniProt ID: SPRN_HUMAN
• Pfam ID: PF14999
• Sequence:
  MNWAPATCWALLLAAAFLCDSGAAKGGRGGARGSARGGVRGGARGASRVRVRPAQRYGAP
  GSSLRVAAAGAAAGAAAGAAAGLAAGSGWRRAAGPGERGLEDEEDGVPGGNGTGPGIYSY
  RAWTSGAGPTRGPRLCLVLGGALGALGLLRP
• Function: Prion-like protein that has PrP(C)-like neuroprotective activity. May act as a modulator for the biological actions of normal and abnormal PrP.
• Tissue Specificity: Mainly expressed in brain. In brain, it is expressed in hippocampus.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Creutzfeldt Jacob disease	DISCB6RX	Strong	Genetic Variation	[1]
Prion disease	DISOUMB0	Strong	Genetic Variation	[2]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Shadow of prion protein (SPRN).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Shadow of prion protein (SPRN).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Shadow of prion protein (SPRN).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Shadow of prion protein (SPRN).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Shadow of prion protein (SPRN).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Shadow of prion protein (SPRN).	[8]

References

• [1] Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats.Sci Rep. 2019 Oct 24;9(1):15261. doi: 10.1038/s41598-019-51625-8.
• [2] Biological properties of the PrP-like Shadoo protein.Front Biosci (Landmark Ed). 2011 Jan 1;16(4):1505-16. doi: 10.2741/3801.
• [3] [6]-Shogaol attenuates inflammation, cell proliferation via modulate NF-B and AP-1 oncogenic signaling in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis.Biomed Pharmacother. 2018 Feb;98:484-490. doi: 10.1016/j.biopha.2017.12.009. Epub 2017 Dec 27.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.