Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTERD9S1)

• DOT Name: Vesicle-trafficking protein SEC22b (SEC22B)
• Synonyms: ER-Golgi SNARE of 24 kDa; ERS-24; ERS24; SEC22 vesicle-trafficking protein homolog B; SEC22 vesicle-trafficking protein-like 1
• Gene Name: SEC22B
• Related Disease: Unverricht-Lundborg syndrome
• UniProt ID: SC22B_HUMAN
• PDB ID: 2NUP; 2NUT; 3EGD; 3EGX
• Pfam ID: PF13774 ; PF00957
• Sequence:
  MVLLTMIARVADGLPLAASMQEDEQSGRDLQQYQSQAKQLFRKLNEQSPTRCTLEAGAMT
  FHYIIEQGVCYLVLCEAAFPKKLAFAYLEDLHSEFDEQHGKKVPTVSRPYSFIEFDTFIQ
  KTKKLYIDSRARRNLGSINTELQDVQRIMVANIEEVLQRGEALSALDSKANNLSSLSKKY
  RQDAKYLNMRSTYAKLAAVAVFFIMLIVYVRFWWL
• Function: SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Phagosome (hsa04145)
  Legionellosis (hsa05134)
• Reactome Pathway:
  COPII-mediated vesicle transport (R-HSA-204005)
  Cargo concentration in the ER (R-HSA-5694530)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[5]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Vesicle-trafficking protein SEC22b (SEC22B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Vesicle-trafficking protein SEC22b (SEC22B).	[8]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Vesicle-trafficking protein SEC22b (SEC22B).	[11]

References

• [1] Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies.Dis Model Mech. 2017 Dec 19;10(12):1391-1398. doi: 10.1242/dmm.029132.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.