Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY2MYBX)

• DOT Name: Synaptosomal-associated protein 23 (SNAP23)
• Synonyms: SNAP-23; Vesicle-membrane fusion protein SNAP-23
• Gene Name: SNAP23
• Related Disease:
  Congenital generalized lipodystrophy
  Generalized lipodystrophy
  Hyperglycemia
  Adenoma
  Cervical cancer
  Cervical carcinoma
  Cystic fibrosis
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Hereditary hemophagocytic lymphohistiocytosis
  Myocardial ischemia
  Neoplasm
  Non-insulin dependent diabetes
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Synovial sarcoma
  Neuroblastoma
• UniProt ID: SNP23_HUMAN
• PDB ID: 1NHL; 3ZUS
• Pfam ID: PF00835
• Sequence:
  MDNLSSEEIQQRAHQITDESLESTRRILGLAIESQDAGIKTITMLDEQKEQLNRIEEGLD
  QINKDMRETEKTLTELNKCCGLCVCPCNRTKNFESGKAYKTTWGDGGENSPCNVVSKQPG
  PVTNGQLQQPTTGAASGGYIKRITNDAREDEMEENLTQVGSILGNLKDMALNIGNEIDAQ
  NPQIKRITDKADTNRDRIDIANARAKKLIDS
• Function: Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion.
• Tissue Specificity: Ubiquitous. Highest levels where found in placenta.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Platelet activation (hsa04611)
• Reactome Pathway:
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)
  trans-Golgi Network Vesicle Budding (R-HSA-199992)
  Neutrophil degranulation (R-HSA-6798695)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOF GTPase cycle (R-HSA-9035034)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital generalized lipodystrophy	DIS4XF8N	Definitive	Biomarker	[1]
Generalized lipodystrophy	DISC6HI8	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Hereditary hemophagocytic lymphohistiocytosis	DISQP21Z	Strong	Genetic Variation	[7]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[5]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[9]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[10]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptosomal-associated protein 23 (SNAP23).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptosomal-associated protein 23 (SNAP23).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synaptosomal-associated protein 23 (SNAP23).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Synaptosomal-associated protein 23 (SNAP23).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Synaptosomal-associated protein 23 (SNAP23).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Synaptosomal-associated protein 23 (SNAP23).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Synaptosomal-associated protein 23 (SNAP23).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Synaptosomal-associated protein 23 (SNAP23).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Synaptosomal-associated protein 23 (SNAP23).	[21]

References

• [1] SNAP23 regulates BAX-dependent adipocyte programmed cell death independently of canonical macroautophagy.J Clin Invest. 2018 Aug 31;128(9):3941-3956. doi: 10.1172/JCI99217. Epub 2018 Aug 13.
• [2] Heterogeneous expression of SNARE proteins SNAP-23, SNAP-25, Syntaxin1 and VAMP in human parathyroid tissue.Mol Cell Endocrinol. 2008 Jun 11;287(1-2):72-80. doi: 10.1016/j.mce.2008.01.028. Epub 2008 Mar 10.
• [3] SNAP23 suppresses cervical cancer progression via modulating the cell cycle.Gene. 2018 Oct 5;673:217-224. doi: 10.1016/j.gene.2018.06.028. Epub 2018 Jun 23.
• [4] Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis.Eur J Hum Genet. 2013 Apr;21(4):397-403. doi: 10.1038/ejhg.2012.181. Epub 2012 Aug 15.
• [5] SNAP23 promotes the malignant process of ovarian cancer.J Ovarian Res. 2016 Nov 17;9(1):80. doi: 10.1186/s13048-016-0289-9.
• [6] Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma.Mol Cancer. 2019 Apr 3;18(1):78. doi: 10.1186/s12943-019-0990-6.
• [7] Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people.J Hum Genet. 2005;50(11):600-603. doi: 10.1007/s10038-005-0293-1. Epub 2005 Sep 23.
• [8] Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
• [9] Proteomic analysis of urinary extracellular vesicles reveal biomarkers for neurologic disease.EBioMedicine. 2019 Jul;45:351-361. doi: 10.1016/j.ebiom.2019.06.021. Epub 2019 Jun 20.
• [10] SNAP-23 and VAMP-3 contribute to the release of IL-6 and TNF from a human synovial sarcoma cell line.FEBS J. 2014 Feb;281(3):750-65. doi: 10.1111/febs.12620. Epub 2013 Dec 13.
• [11] Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells.Oncotarget. 2016 May 31;7(22):33220-8. doi: 10.18632/oncotarget.8903.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.