Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG5H3YF)

• DOT Name: Extended synaptotagmin-3 (ESYT3)
• Synonyms: E-Syt3; Chr3Syt
• Gene Name: ESYT3
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
• UniProt ID: ESYT3_HUMAN
• Pfam ID: PF00168 ; PF17047
• Sequence:
  MRAEEPCAPGAPSALGAQRTPGPELRLSSQLLPELCTFVVRVLFYLGPVYLAGYLGLSIT
  WLLLGALLWMWWRRNRRGKLGRLAAAFEFLDNEREFISRELRGQHLPAWIHFPDVERVEW
  ANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTN
  TCNRRRVTVDLQICYIGDCEISVELQKIQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTV
  FFLQKPHLQINWTGLTNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKKGLDLTNLR
  FPLPCGVIRVHLLEAEQLAQKDNFLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEV
  FEFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLHL
  RLEWLSLLTDQEVLTEDHGGLSTAILVVFLESACNLPRNPFDYLNGEYRAKKLSRFARNK
  VSKDPSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECAL
  GMLEVPLCQILPYADLTLEQRFQLDHSGLDSLISMRLVLRFLQVEERELGSPYTGPEALK
  KGPLLIKKVATNQGPKAQPQEEGPTDLPCPPDPASDTKDVSRSTTTTTSATTVATEPTSQ
  ETGPEPKGKDSAKRFCEPIGEKKSPATIFLTVPGPHSPGPIKSPRPMKCPASPFAWPPKR
  LAPSMSSLNSLASSCFDLADISLNIEGGDLRRRQLGEIQLTVRYVCLRRCLSVLINGCRN
  LTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVKKRSLDV
  AVKNSRPLGSHRRKELGKVLIDLSKEDLIKGFSQWYELTPNGQPRS
• Function: Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane.
• Tissue Specificity: Widely expressed with high level in cerebellum and skin.
• Reactome Pathway: Glycosphingolipid biosynthesis (R-HSA-9840309)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[1]

4 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 Extended synaptotagmin-3 (ESYT3).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Extended synaptotagmin-3 (ESYT3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Extended synaptotagmin-3 (ESYT3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Extended synaptotagmin-3 (ESYT3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Extended synaptotagmin-3 (ESYT3).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Extended synaptotagmin-3 (ESYT3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Extended synaptotagmin-3 (ESYT3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Extended synaptotagmin-3 (ESYT3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Extended synaptotagmin-3 (ESYT3).	[9]

References

• [1] Fine mapping of chromosome 3q22.3 identifies two haplotype blocks in ESYT3 associated with coronary artery disease in female Han Chinese.Atherosclerosis. 2011 Oct;218(2):397-403. doi: 10.1016/j.atherosclerosis.2011.06.017. Epub 2011 Jun 17.
• [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] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [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.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.