Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSAGTP6)

• DOT Name: Vesicle-trafficking protein SEC22a (SEC22A)
• Synonyms: SEC22 vesicle-trafficking protein homolog A; SEC22 vesicle-trafficking protein-like 2
• Gene Name: SEC22A
• Related Disease: Parkinson disease
• UniProt ID: SC22A_HUMAN
• Pfam ID: PF13774
• Sequence:
  MSMILSASVIRVRDGLPLSASTDYEQSTGMQECRKYFKMLSRKLAQLPDRCTLKTGHYNI
  NFISSLGVSYMMLCTENYPNVLAFSFLDELQKEFITTYNMMKTNTAVRPYCFIEFDNFIQ
  RTKQRYNNPRSLSTKINLSDMQTEIKLRPPYQISMCELGSANGVTSAFSVDCKGAGKISS
  AHQRLEPATLSGIVGFILSLLCGALNLIRGFHAIESLLQSDGDDFNYIIAFFLGTAACLY
  QCYLLVYYTGWRNVKSFLTFGLICLCNMYLYELRNLWQLFFHVTVGAFVTLQIWLRQAQG
  KAPDYDV
• Function: May be involved in vesicle transport between the ER and the Golgi complex.
• Reactome Pathway: COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Biomarker	[1]

3 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 Vesicle-trafficking protein SEC22a (SEC22A).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Vesicle-trafficking protein SEC22a (SEC22A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Vesicle-trafficking protein SEC22a (SEC22A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Vesicle-trafficking protein SEC22a (SEC22A).	[14]

References

• [1] Aegeline, a natural product from the plant Aegle marmelos, mimics the yeast SNARE protein Sec22p in suppressing -synuclein and Bax toxicity in yeast.Bioorg Med Chem Lett. 2019 Feb 1;29(3):454-460. doi: 10.1016/j.bmcl.2018.12.028. Epub 2018 Dec 13.
• [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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.