Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4BXRNV)

• DOT Name: Syntaxin-binding protein 4 (STXBP4)
• Synonyms: Syntaxin 4-interacting protein; STX4-interacting protein; Synip
• Gene Name: STXBP4
• UniProt ID: STXB4_HUMAN
• PDB ID: 2YSG
• Pfam ID: PF00595 ; PF00397
• Sequence:
  MNKNTSTVVSPSLLEKDPAFQMITIAKETGLGLKVLGGINRNEGPLVYIQEIIPGGDCYK
  DGRLKPGDQLVSVNKESMIGVSFEEAKSIITGAKLRLESAWEIAFIRQKSDNIQPENLSC
  TSLIEASGEYGPQASTLSLFSSPPEILIPKTSSTPKTNNDILSSCEIKTGYNKTVQIPIT
  SENSTVGLSNTDVASAWTENYGLQEKISLNPSVRFKAEKLEMALNYLGIQPTKEQHQALR
  QQVQADSKGTVSFGDFVQVARNLFCLQLDEVNVGAHEISNILDSQLLPCDSSEADEMERL
  KCERDDALKEVNTLKEKLLESDKQRKQLTEELQNVKQEAKAVVEETRALRSRIHLAEAAQ
  RQAHGMEMDYEEVIRLLEAKITELKAQLADYSDQNKESVQDLKKRIMVLDCQLRKSEMAR
  KTFEASTEKLLHFVEAIQEVFSDNSTPLSNLSERRAVLASQTSLTPLGRNGRSIPATLAL
  ESKELVKSVRALLDMDCLPYGWEEAYTADGIKYFINHVTQTTSWIHPVMSVLNLSRSEEN
  EEDCSRELPNQKS
• Function: Plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane. Inhibits the translocation of SLC2A4 from intracellular vesicles to the plasma membrane by STX4A binding and preventing the interaction between STX4A and VAMP2. Stimulation with insulin disrupts the interaction with STX4A, leading to increased levels of SLC2A4 at the plasma membrane. May also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose.

Molecular Interaction Atlas (MIA) of This DOT

7 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 Syntaxin-binding protein 4 (STXBP4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Syntaxin-binding protein 4 (STXBP4).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-binding protein 4 (STXBP4).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syntaxin-binding protein 4 (STXBP4).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Syntaxin-binding protein 4 (STXBP4).	[5]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Syntaxin-binding protein 4 (STXBP4).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Syntaxin-binding protein 4 (STXBP4).	[8]

1 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 Syntaxin-binding protein 4 (STXBP4).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.