Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFZQV17)

• DOT Name: Sorting nexin-33 (SNX33)
• Synonyms: SH3 and PX domain-containing protein 3
• Gene Name: SNX33
• UniProt ID: SNX33_HUMAN
• PDB ID: 4AKV
• Pfam ID: PF10456 ; PF00787 ; PF14604
• Sequence:
  MALKGRALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEIVR
  SGISTNHADYSSSPAGSPGAQVSLYNSPSVASPARSGGGSGFLSNQGSFEEDDDDDWDDW
  DDGCTVVEEPRAGGLGTNGHPPLNLSYPGAYPSQHMAFRPKPPLERQDSLASAKRGSVVG
  RNLNRFSCFVRSGVEAFILGDVPMMAKIAETYSIEMGPRGPQWKANPHPFACSVEDPTKQ
  TKFKGIKSYISYKLTPTHAASPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEE
  DFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLSCLDDKQWKMGKRRAEKDEMVGASFLL
  TFQIPTEHQDLQDVEDRVDTFKAFSKKMDDSVLQLSTVASELVRKHVGGFRKEFQKLGSA
  FQAISHSFQMDPPFCSEALNSAISHTGRTYEAIGEMFAEQPKNDLFQMLDTLSLYQGLLS
  NFPDIIHLQKGAFAKVKESQRMSDEGRMVQDEADGIRRRCRVVGFALQAEMNHFHQRREL
  DFKHMMQNYLRQQILFYQRVGQQLEKTLRMYDNL
• Function: Plays a role in the reorganization of the cytoskeleton, endocytosis and cellular vesicle trafficking via its interactions with membranes, WASL, DNM1 and DNM2. Acts both during interphase and at the end of mitotic cell divisions. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Modulates endocytosis of cell-surface proteins, such as APP and PRNP; this then modulates the secretion of APP and PRNP peptides. Promotes membrane tubulation (in vitro). May promote the formation of macropinosomes.
• Tissue Specificity: Detected in heart and pancreas.
• KEGG Pathway: Salmonella infection (hsa05132)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sorting nexin-33 (SNX33).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sorting nexin-33 (SNX33).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sorting nexin-33 (SNX33).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sorting nexin-33 (SNX33).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sorting nexin-33 (SNX33).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Sorting nexin-33 (SNX33).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sorting nexin-33 (SNX33).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sorting nexin-33 (SNX33).	[7]

2 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 affects the phosphorylation of Sorting nexin-33 (SNX33).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Sorting nexin-33 (SNX33).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [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.