Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT86PAFL)

• DOT Name: Synaptotagmin-12 (SYT12)
• Synonyms: Synaptotagmin XII; SytXII
• Gene Name: SYT12
• Related Disease: Oral cancer
• UniProt ID: SYT12_HUMAN
• Pfam ID: PF00168
• Sequence:
  MAVDVAEYHLSVIKSPPGWEVGVYAAGALALLGIAAVSLWKLWTSGSFPSPSPFPNYDYR
  YLQQKYGESCAEAREKRVPAWNAQRASTRGPPSRKGSLSIEDTFESISELGPLELMGREL
  DLAPYGTLRKSQSADSLNSISSVSNTFGQDFTLGQVEVSMEYDTASHTLNVAVMQGKDLL
  EREEASFESCFMRVSLLPDEQIVGISRIQRNAYSIFFDEKFSIPLDPTALEEKSLRFSVF
  GIDEDERNVSTGVVELKLSVLDLPLQPFSGWLYLQDQNKAADAVGEILLSLSYLPTAERL
  TVVVVKAKNLIWTNDKTTADPFVKVYLLQDGRKMSKKKTAVKRDDPNPVFNEAMIFSVPA
  IVLQDLSLRVTVAESSSDGRGDNVGHVIIGPSASGMGTTHWNQMLATLRRPVSMWHAVRR
  N
• Function: Synaptic vesicle phosphoprotein that enhances spontaneous neurotransmitter release but does not effect induced neurotransmitter release. Unlike other synaptotagmins, it does not bind Ca(2+) or phospholipids. Essential for mossy-fiber long-term potentiation in the hippocampus.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral cancer	DISLD42D	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptotagmin-12 (SYT12).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptotagmin-12 (SYT12).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Synaptotagmin-12 (SYT12).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Synaptotagmin-12 (SYT12).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Synaptotagmin-12 (SYT12).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Synaptotagmin-12 (SYT12).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Synaptotagmin-12 (SYT12).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Synaptotagmin-12 (SYT12).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptotagmin-12 (SYT12).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Synaptotagmin-12 (SYT12).	[6]

References

• [1] SYT12 plays a critical role in oral cancer and may be a novel therapeutic target.J Cancer. 2019 Aug 27;10(20):4913-4920. doi: 10.7150/jca.32582. eCollection 2019.
• [2] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.