Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2FBS5N)

• DOT Name: SNARE-associated protein Snapin (SNAPIN)
• Synonyms: Biogenesis of lysosome-related organelles complex 1 subunit 7; BLOC-1 subunit 7; Synaptosomal-associated protein 25-binding protein; SNAP-associated protein
• Gene Name: SNAPIN
• Related Disease:
  Autoimmune disease
  Hepatocellular carcinoma
  Rheumatoid arthritis
• UniProt ID: SNAPN_HUMAN
• Pfam ID: PF14712
• Sequence:
  MAGAGSAAVSGAGTPVAGPTGRDLFAEGLLEFLRPAVQQLDSHVHAVRESQVELREQIDN
  LATELCRINEDQKVALDLDPYVKKLLNARRRVVLVNNILQNAQERLRRLNHSVAKETARR
  RAMLDSGIYPPGSPGK
• Function: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling. May modulate a step between vesicle priming, fusion and calcium-dependent neurotransmitter release through its ability to potentiate the interaction of synaptotagmin with the SNAREs and the plasma-membrane-associated protein SNAP25. Its phosphorylation state influences exocytotic protein interactions and may regulate synaptic vesicle exocytosis. May also have a role in the mechanisms of SNARE-mediated membrane fusion in non-neuronal cells. As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.
• Tissue Specificity: Expressed in male germ cells of adult testis (at protein level).
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of SNARE-associated protein Snapin (SNAPIN).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SNARE-associated protein Snapin (SNAPIN).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of SNARE-associated protein Snapin (SNAPIN).	[12]

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 affects the phosphorylation of SNARE-associated protein Snapin (SNAPIN).	[11]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of SNARE-associated protein Snapin (SNAPIN).	[13]

References

• [1] SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages.Autophagy. 2017 Feb;13(2):285-301. doi: 10.1080/15548627.2016.1261238. Epub 2016 Dec 8.
• [2] CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma.Cancer Genet Cytogenet. 2008 Jan 1;180(1):30-6. doi: 10.1016/j.cancergencyto.2007.09.013.
• [3] SNAPIN: an endogenous Toll-like receptor ligand in rheumatoid arthritis.Ann Rheum Dis. 2012 Aug;71(8):1411-7. doi: 10.1136/annrheumdis-2011-200899. Epub 2012 Apr 20.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] 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.