Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2I652M)

• DOT Name: Sorting nexin-17 (SNX17)
• Gene Name: SNX17
• Related Disease:
  Atrial fibrillation
  Gout
  Myocardial infarction
• UniProt ID: SNX17_HUMAN
• PDB ID: 3FOG; 3LUI; 4GXB; 4TKN; 7RM8
• Pfam ID: PF00787 ; PF21273 ; PF21271 ; PF18116
• Sequence:
  MHFSIPETESRSGDSGGSAYVAYNIHVNGVLHCRVRYSQLLGLHEQLRKEYGANVLPAFP
  PKKLFSLTPAEVEQRREQLEKYMQAVRQDPLLGSSETFNSFLRRAQQETQQVPTEEVSLE
  VLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREKEDGAFSFVRKLQ
  EFELPYVSVTSLRSQEYKIVLRKSYWDSAYDDDVMENRVGLNLLYAQTVSDIERGWILVT
  KEQHRQLKSLQEKVSKKEFLRLAQTLRHYGYLRFDACVADFPEKDCPVVVSAGNSELSLQ
  LRLPGQQLREGSFRVTRMRCWRVTSSVPLPSGSTSSPGRGRGEVRLELAFEYLMSKDRLQ
  WVTITSPQAIMMSICLQSMVDELMVKKSGGSIRKMLRRRVGGTLRRSDSQQAVKSPPLLE
  SPDATRESMVKLSSKLSAVSLRGIGSPSTDASASDVHGNFAFEGIGDEDL
• Function: Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Associates with retriever and CCC complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGB1, ITGB5 and their associated alpha subunits. Also required for maintenance of normal cell surface levels of APP and LRP1. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
Gout	DISHC0U7	Strong	Genetic Variation	[2]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[3]

3 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 Sorting nexin-17 (SNX17).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sorting nexin-17 (SNX17).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Sorting nexin-17 (SNX17).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sorting nexin-17 (SNX17).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sorting nexin-17 (SNX17).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sorting nexin-17 (SNX17).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Sorting nexin-17 (SNX17).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Sorting nexin-17 (SNX17).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sorting nexin-17 (SNX17).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Sorting nexin-17 (SNX17).	[11]

References

• [1] SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.Circ Arrhythm Electrophysiol. 2019 Apr;12(4):e007097. doi: 10.1161/CIRCEP.118.007097.
• [2] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [3] SNX17 produces anti-arrhythmic effects by preserving functional SERCA2a protein in myocardial infarction.Int J Cardiol. 2018 Dec 1;272:298-305. doi: 10.1016/j.ijcard.2018.07.025. Epub 2018 Jul 4.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.