Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTW4MI3)

• DOT Name: Synaptotagmin-17 (SYT17)
• Synonyms: Protein B/K; Synaptotagmin XVII; SytXVII
• Gene Name: SYT17
• Related Disease: Parkinson disease
• UniProt ID: SYT17_HUMAN
• PDB ID: 2ENP
• Pfam ID: PF00168
• Sequence:
  MAYIQLEPLNEGFLSRISGLLLCRWTCRHCCQKCYESSCCQSSEDEVEILGPFPAQTPPW
  LMASRSSDKDGDSVHTASEVPLTPRTNSPDGRRSSSDTSKSTYSLTRRISSLESRRPSSP
  LIDIKPIEFGVLSAKKEPIQPSVLRRTYNPDDYFRKFEPHLYSLDSNSDDVDSLTDEEIL
  SKYQLGMLHFSTQYDLLHNHLTVRVIEARDLPPPISHDGSRQDMAHSNPYVKICLLPDQK
  NSKQTGVKRKTQKPVFEERYTFEIPFLEAQRRTLLLTVVDFDKFSRHCVIGKVSVPLCEV
  DLVKGGHWWKALIPSSQNEVELGELLLSLNYLPSAGRLNVDVIRAKQLLQTDVSQGSDPF
  VKIQLVHGLKLVKTKKTSFLRGTIDPFYNESFSFKVPQEELENASLVFTVFGHNMKSSND
  FIGRIVIGQYSSGPSETNHWRRMLNTHRTAVEQWHSLRSRAECDRVSPASLEVT
• Function: Plays a role in dendrite formation by melanocytes.
• Tissue Specificity: Expressed abundantly in brain (frontal and temporal lobes, hippocampus, hypothalamus, amygdala, substantia nigra, and pituitary), kidney, and prostate. Expressed in fetal brain, kidney and lung . Expressed in melanocytes .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]

1 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 Synaptotagmin-17 (SYT17).	[2]

11 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 Synaptotagmin-17 (SYT17).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptotagmin-17 (SYT17).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptotagmin-17 (SYT17).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Synaptotagmin-17 (SYT17).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Synaptotagmin-17 (SYT17).	[7]
Aripiprazole	DM3NUMH	Approved	Aripiprazole decreases the expression of Synaptotagmin-17 (SYT17).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Synaptotagmin-17 (SYT17).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Synaptotagmin-17 (SYT17).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Synaptotagmin-17 (SYT17).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Synaptotagmin-17 (SYT17).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Synaptotagmin-17 (SYT17).	[13]

References

• [1] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Small Molecule Antipsychotic Aripiprazole Potentiates Ozone-Induced Inflammation in Airway Epithelium. Chem Res Toxicol. 2019 Oct 21;32(10):1997-2005. doi: 10.1021/acs.chemrestox.9b00149. Epub 2019 Sep 11.
• [9] 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.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] 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.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.