Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE3F36L)

• DOT Name: Synaptotagmin-6 (SYT6)
• Synonyms: Synaptotagmin VI; SytVI
• Gene Name: SYT6
• Related Disease:
  Clear cell renal carcinoma
  Renal cell carcinoma
  Venous thromboembolism
  Rett syndrome
• UniProt ID: SYT6_HUMAN
• Pfam ID: PF00168
• Sequence:
  MSGVWGAGGPRCQEALAVLASLCRARPPPLGLDVETCRSFELQPPERSPSAAGAGTSVSL
  LAVVVIVCGVALVAVFLFLFWKLCWMPWRNKEASSPSSANPPLEALQSPSFRGNMADKLK
  DPSTLGFLEAAVKISHTSPDIPAEVQMSVKEHIMRHTRLQRQTTEPASSTRHTSFKRHLP
  RQMHVSSVDYGNELPPAAEQPTSIGRIKPELYKQKSVDGEDAKSEATKSCGKINFSLRYD
  YETETLIVRILKAFDLPAKDFCGSSDPYVKIYLLPDRKCKLQTRVHRKTLNPTFDENFHF
  PVPYEELADRKLHLSVFDFDRFSRHDMIGEVILDNLFEASDLSRETSIWKDIQYATSESV
  DLGEIMFSLCYLPTAGRLTLTVIKCRNLKAMDITGYSDPYVKVSLLCDGRRLKKKKTTIK
  KNTLNPVYNEAIIFDIPPENMDQVSLLISVMDYDRVGHNEIIGVCRVGITAEGLGRDHWN
  EMLAYPRKPIAHWHSLVEVKKSFKEGNPRL
• 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. May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[1]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[2]
Rett syndrome	DISGG5UV	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Synaptotagmin-6 (SYT6).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Synaptotagmin-6 (SYT6).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptotagmin-6 (SYT6).	[5]

References

• [1] Identification of novel epigenetic markers for clear cell renal cell carcinoma.J Urol. 2008 Sep;180(3):1126-30. doi: 10.1016/j.juro.2008.04.137. Epub 2008 Jul 18.
• [2] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [3] Analysis of gene expression in Ca(2+)-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways.Neurosci Lett. 2017 Feb 3;639:88-93. doi: 10.1016/j.neulet.2016.12.068. Epub 2016 Dec 29.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.