Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT718PRY)

• DOT Name: Synaptotagmin-5 (SYT5)
• Synonyms: Synaptotagmin V; SytV
• Gene Name: SYT5
• Related Disease: Type-1/2 diabetes
• UniProt ID: SYT5_HUMAN
• PDB ID: 5H4Y; 5H4Z
• Pfam ID: PF00168
• Sequence:
  MFPEPPTPGPPSPDTPPDSSRISHGPVPPWALATIVLVSGLLIFSCCFCLYRKSCRRRTG
  KKSQAQAQVHLQEVKGLGQSYIDKVQPEVEELEPAPSGPGQQVADKHELGRLQYSLDYDF
  QSGQLLVGILQAMGLAALDLGGSSDPYVRVYLLPDKRRRYETKVHRQTLNPHFGETFAFK
  VPYVELGGRVLVMAVYDFDRFSRNDAIGEVRVPMSSVDLGRPVQAWRELQAAPREEQEKL
  GDICFSLRYVPTAGKLTVIVLEAKNLKKMDVGGLSDPYVKVHLLQGGKKVRKKKTTIKKN
  TLNPYYNEAFSFEVPCDQVQKVQVELTVLDYDKLGKNEAIGRVAVGAAAGGAGLRHWADM
  LANPRRPIAQWHSLRPPDRVRLLPAP
• Function: May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Regulates the Ca(2+)-dependent secretion of norepinephrine in PC12 cells. Required for export from the endocytic recycling compartment to the cell surface.
• Reactome Pathway: Regulation of insulin secretion (R-HSA-422356)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[1]

3 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-5 (SYT5).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Synaptotagmin-5 (SYT5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Synaptotagmin-5 (SYT5).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptotagmin-5 (SYT5).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Synaptotagmin-5 (SYT5).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Synaptotagmin-5 (SYT5).	[6]

References

• [1] Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients.Diabetes. 2006 Feb;55(2):435-40. doi: 10.2337/diabetes.55.02.06.db04-1575.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] 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.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.