Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT125UGP)

• DOT Name: Inhibitory synaptic factor 2A (INSYN2A)
• Synonyms: InSyn2
• Gene Name: INSYN2A
• UniProt ID: INSY2_HUMAN
• Pfam ID: PF15265
• Sequence:
  MVSKDTGKCILTTSESEVEPAACLALEMKYALDPNRQIKKRNKALQVRFKDICEAQNEQR
  DTQLSSGQLGEKREAKPVSCRAAYRKYMTVPARRSIPNVTKSTGVQTSPDLKKCYQTFPL
  DRKKGNLKSLPAADPFKSQNNGFLTDAKEKNEAGPMEEARPCGAGRVHKTTALVFHSNQH
  MNTVDQPLGVNCTEPCKSPEPLSYGEAALQNSTRPPSEEPDYQLLGRAKQDRGRPNSEEP
  APPALRRVFKTEVATVYAPALSARAPEPGLSDSAAASQWSLCPADDERRRATHLNGLQAP
  SETALACSPPMQCLSPECSEQPSQTHTPPGLGNQPSPTAVAAGEECQRIVPHTEVVDLKA
  QLQMMENLISSSQETIKVLLGVIQELEKGEAHREGLSYRTGQDTANCDTCRNSACIIYSV
  ELDFKQQEDKLQPVLRKLHPIEETQVIPSPYSQETYSSTPKQKSKTESKKHGRWKLWFL
• Function: Component of the protein machinery at the inhibitory synapses, probably acting as a scaffold. Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. This synaptic inhibition is fundamental for the functioning of the central nervous system, shaping and orchestrating the flow of information through neuronal networks to generate a precise neural code.

Molecular Interaction Atlas (MIA) of This DOT

1 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 Inhibitory synaptic factor 2A (INSYN2A).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Inhibitory synaptic factor 2A (INSYN2A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inhibitory synaptic factor 2A (INSYN2A).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inhibitory synaptic factor 2A (INSYN2A).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Inhibitory synaptic factor 2A (INSYN2A).	[5]

References

• [1] 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.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.