Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT68KT3X)

• DOT Name: Sorting nexin-18 (SNX18)
• Synonyms: SH3 and PX domain-containing protein 3B
• Gene Name: SNX18
• UniProt ID: SNX18_HUMAN
• Pfam ID: PF10456 ; PF00787 ; PF14604
• Sequence:
  MALRARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVQVIR
  APEPGPAGDGGPGAPARYANVPPGGFEPLPVAPPASFKPPPDAFQALLQPQQAPPPSTFQ
  PPGAGFPYGGGALQPSPQQLYGGYQASQGSDDDWDDEWDDSSTVADEPGALGSGAYPDLD
  GSSSAGVGAAGRYRLSTRSDLSLGSRGGSVPPQHHPSGPKSSATVSRNLNRFSTFVKSGG
  EAFVLGEASGFVKDGDKLCVVLGPYGPEWQENPYPFQCTIDDPTKQTKFKGMKSYISYKL
  VPTHTQVPVHRRYKHFDWLYARLAEKFPVISVPHLPEKQATGRFEEDFISKRRKGLIWWM
  NHMASHPVLAQCDVFQHFLTCPSSTDEKAWKQGKRKAEKDEMVGANFFLTLSTPPAAALD
  LQEVESKIDGFKCFTKKMDDSALQLNHTANEFARKQVTGFKKEYQKVGQSFRGLSQAFEL
  DQQAFSVGLNQAIAFTGDAYDAIGELFAEQPRQDLDPVMDLLALYQGHLANFPDIIHVQK
  GKAWPLEQVIWSVLCRLKGATLTAVPLWVSESYSTGEEASRDVDAWVFSLECKLDCSTGS
  FLLEYLALGNEYSFSKVQRVPLMTVLSF
• Function: Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Stimulates the GTPase activity of DNM2. Promotes DNM2 location at the plasma membrane. Together with DNM2, involved in autophagosome assembly by regulating trafficking from recycling endosomes of phospholipid scramblase ATG9A.
• KEGG Pathway: Salmonella infection (hsa05132)
• Reactome Pathway: Clathrin-mediated endocytosis (R-HSA-8856828)

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 Sorting nexin-18 (SNX18).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sorting nexin-18 (SNX18).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sorting nexin-18 (SNX18).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sorting nexin-18 (SNX18).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Sorting nexin-18 (SNX18).	[4]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Sorting nexin-18 (SNX18).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sorting nexin-18 (SNX18).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Sorting nexin-18 (SNX18).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sorting nexin-18 (SNX18).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sorting nexin-18 (SNX18).	[10]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [6] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] 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.
• [9] 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.
• [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.