Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ71L5Y)

• DOT Name: Sorting nexin-4 (SNX4)
• Gene Name: SNX4
• UniProt ID: SNX4_HUMAN
• Pfam ID: PF00787
• Sequence:
  MEQAPPDPERQLQPAPLEPLGSPDAGLGAAVGKEAEGAGEESSGVDTMTHNNFWLKKIEI
  SVSEAEKRTGRNAMNMQETYTAYLIETRSVEHTDGQSVLTDSLWRRYSEFELLRSYLLVY
  YPHIVVPPLPEKRAEFVWHKLSADNMDPDFVERRRIGLENFLLRIASHPILCRDKIFYLF
  LTQEGNWKETVNETGFQLKADSRLKALNATFRVKNPDKRFTDLKHYSDELQSVISHLLRV
  RARVADRLYGVYKVHGNYGRVFSEWSAIEKEMGDGLQSAGHHMDVYASSIDDILEDEEHY
  ADQLKEYLFYAEALRAVCRKHELMQYDLEMAAQDLASKKQQCEELVTGTVRTFSLKGMTT
  KLFGQETPEQREARIKVLEEQINEGEQQLKSKNLEGREFVKNAWADIERFKEQKNRDLKE
  ALISYAVMQISMCKKGIQVWTNAKECFSKM
• Function: Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Plays a role in recycling endocytosed transferrin receptor and prevent its degradation. Involved in autophagosome assembly by regulating trafficking and recycling of phospholipid scramblase ATG9A.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

9 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-4 (SNX4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sorting nexin-4 (SNX4).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sorting nexin-4 (SNX4).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sorting nexin-4 (SNX4).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Sorting nexin-4 (SNX4).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sorting nexin-4 (SNX4).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sorting nexin-4 (SNX4).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sorting nexin-4 (SNX4).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sorting nexin-4 (SNX4).	[9]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.