Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYQ0TV4)

• DOT Name: Sorting nexin-16 (SNX16)
• Gene Name: SNX16
• UniProt ID: SNX16_HUMAN
• PDB ID: 5GW0; 5GW1
• Pfam ID: PF00787
• Sequence:
  MATPYVPVPMPIGNSASSFTTNRNQRSSSFGSVSTSSNSSKGQLEDSNMGNFKQTSVPDQ
  MDNTSSVCSSPLIRTKFTGTASSIEYSTRPRDTEEQNPETVNWEDRPSTPTILGYEVMEE
  RAKFTVYKILVKKTPEESWVVFRRYTDFSRLNDKLKEMFPGFRLALPPKRWFKDNYNADF
  LEDRQLGLQAFLQNLVAHKDIANCLAVREFLCLDDPPGPFDSLEESRAFCETLEETNYRL
  QKELLEKQKEMESLKKLLSEKQLHIDTLENRIRTLSLEPEESLDVSETEGEQILKVESSA
  LEVDQDVLDEESRADNKPCLSFSEPENAVSEIEVAEVAYDAEED
• Function: May be involved in several stages of intracellular trafficking. Plays a role in protein transport from early to late endosomes. Plays a role in protein transport to the lysosome. Promotes degradation of EGFR after EGF signaling. Plays a role in intracellular transport of vesicular stomatitis virus nucleocapsids from the endosome to the cytoplasm.
• Tissue Specificity: Detected in placenta, lung, liver,heart and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Sorting nexin-16 (SNX16) affects the response to substance of NAPQI.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Sorting nexin-16 (SNX16).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sorting nexin-16 (SNX16).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sorting nexin-16 (SNX16).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sorting nexin-16 (SNX16).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Sorting nexin-16 (SNX16).	[4]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Sorting nexin-16 (SNX16).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Sorting nexin-16 (SNX16).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sorting nexin-16 (SNX16).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sorting nexin-16 (SNX16).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sorting nexin-16 (SNX16).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sorting nexin-16 (SNX16).	[11]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [5] Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells. Lipids Health Dis. 2010 Jun 2;9:56. doi: 10.1186/1476-511X-9-56.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.