Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVV19BW)

• DOT Name: Synaptotagmin-10 (SYT10)
• Synonyms: Synaptotagmin X; SytX
• Gene Name: SYT10
• Related Disease: Nervous system disease
• UniProt ID: SYT10_HUMAN
• Pfam ID: PF00168
• Sequence:
  MSFHKEDGVNSLCQKALHIVTELCFAGQVEWEKCSGIFPRDRGSQGGSSTDISVSLLAVV
  VSFCGLALLVVSLFVFWKLCWPCWKSKPVTSNITTLPQSISSAPTEVFETEEKKEIKENE
  KPAVKAIEPAIKISHTSPDIPAEVQTALKEHLIKHARVQRQITEPTSSTRHSSFRRHLPR
  QMQVSSVDFSMGTEPVLQRGETTTSIGRIKPELYKQKSVDSEGNQNEDVKICGKLNFTLQ
  YDYENELLVVKIIKALDLPAKDFTGTSDPYVKMYLLPDRKKKFQTRVHRKTLNPLFDETF
  QFPVAYDQLSNRKLHFSVYDFDRFSRHDMIGEVILDNLFEVSDLSREATVWKDIHCATTE
  SIDLGEIMFSLCYLPTAGRMTLTVIKCRNLKAMDITGSSDPYVKVSLMCEGRRLKKRKTT
  TKKNTLNPVYNEAIIFDIPPENVDQVSLSIAVMDYDRVGHNEVIGVCRTGLDAEGLGRDH
  WNEMLAYHRKPITHWHPLLELPGRATSFDSQGSCPSPKPPSTP
• Function: Ca(2+) sensor specifically required for the Ca(2+)-dependent exocytosis of secretory vesicles containing IGF1 in neurons of the olfactory bulb. Exocytosis of IGF1 is required for sensory perception of smell. Not involved in Ca(2+)-dependent synaptic vesicle exocytosis. Acts through Ca(2+) and phospholipid binding to the C2 domain: Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis.
• Tissue Specificity: Expressed only in pancreas, lung and kidney.
• Reactome Pathway:
  NPAS4 regulates expression of target genes (R-HSA-9768919)
  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
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Synaptotagmin-10 (SYT10).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Synaptotagmin-10 (SYT10).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Synaptotagmin-10 (SYT10).	[4]

References

• [1] Identification of Synaptotagmin 10 as Effector of NPAS4-Mediated Protection from Excitotoxic Neurodegeneration.J Neurosci. 2016 Mar 2;36(9):2561-70. doi: 10.1523/JNEUROSCI.2027-15.2016.
• [2] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [3] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [4] Assessment of caffeine neurotoxicity using novel biomarkers of neural function in SH-SY5Y cells - Is there a need for environmental concern?. Chem Biol Interact. 2022 Sep 25;365:110082. doi: 10.1016/j.cbi.2022.110082. Epub 2022 Aug 5.