Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG1BGGO)

• DOT Name: Alpha-soluble NSF attachment protein (NAPA)
• Synonyms: SNAP-alpha; N-ethylmaleimide-sensitive factor attachment protein alpha
• Gene Name: NAPA
• Related Disease:
  Epilepsy
  Hydrocephalus
• UniProt ID: SNAA_HUMAN
• Pfam ID: PF14938
• Sequence:
  MDNSGKEAEAMALLAEAERKVKNSQSFFSGLFGGSSKIEEACEIYARAANMFKMAKNWSA
  AGNAFCQAAQLHLQLQSKHDAATCFVDAGNAFKKADPQEAINCLMRAIEIYTDMGRFTIA
  AKHHISIAEIYETELVDIEKAIAHYEQSADYYKGEESNSSANKCLLKVAGYAALLEQYQK
  AIDIYEQVGTNAMDSPLLKYSAKDYFFKAALCHFCIDMLNAKLAVQKYEELFPAFSDSRE
  CKLMKKLLEAHEEQNVDSYTESVKEYDSISRLDQWLTTMLLRIKKTIQGDEEDLR
• Function: Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus (Probable). Together with GNA12 promotes CDH5 localization to plasma membrane.
• KEGG Pathway: Sy.ptic vesicle cycle (hsa04721)
• Reactome Pathway:
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Intra-Golgi traffic (R-HSA-6811438)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Strong	Biomarker	[1]
Hydrocephalus	DISIZUF7	Limited	Genetic Variation	[2]

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 Alpha-soluble NSF attachment protein (NAPA).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alpha-soluble NSF attachment protein (NAPA).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-soluble NSF attachment protein (NAPA).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-soluble NSF attachment protein (NAPA).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Alpha-soluble NSF attachment protein (NAPA).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Alpha-soluble NSF attachment protein (NAPA).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Alpha-soluble NSF attachment protein (NAPA).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-soluble NSF attachment protein (NAPA).	[10]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Alpha-soluble NSF attachment protein (NAPA).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Alpha-soluble NSF attachment protein (NAPA).	[12]

References

• [1] Association of Alpha-Soluble NSF Attachment Protein with Epileptic Seizure.J Mol Neurosci. 2015 Nov;57(3):417-25. doi: 10.1007/s12031-015-0596-4. Epub 2015 Jul 9.
• [2] Pleiotropic effects of alpha-SNAP M105I mutation on oocyte biology: ultrastructural and cellular changes that adversely affect female fertility in mice.Sci Rep. 2019 Nov 22;9(1):17374. doi: 10.1038/s41598-019-53574-8.
• [3] 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.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 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.
• [7] 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.
• [8] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [9] 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.
• [10] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [11] Proteomic analysis of proteins associated with cellular senescence by calorie restriction in mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 2012 Mar;48(3):186-95.
• [12] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.