Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4WS64)

• DOT Name: Gamma-soluble NSF attachment protein (NAPG)
• Synonyms: SNAP-gamma; N-ethylmaleimide-sensitive factor attachment protein gamma
• Gene Name: NAPG
• Related Disease:
  Bipolar disorder
  Frontotemporal dementia
  Pick disease
  Retinoblastoma
• UniProt ID: SNAG_HUMAN
• Pfam ID: PF14938
• Sequence:
  MAAQKINEGLEHLAKAEKYLKTGFLKWKPDYDSAASEYGKAAVAFKNAKQFEQAKDACLR
  EAVAHENNRALFHAAKAYEQAGMMLKEMQKLPEAVQLIEKASMMYLENGTPDTAAMALER
  AGKLIENVDPEKAVQLYQQTANVFENEERLRQAVELLGKASRLLVRGRRFDEAALSIQKE
  KNIYKEIENYPTCYKKTIAQVLVHLHRNDYVAAERCVRESYSIPGFNGSEDCAALEQLLE
  GYDQQDQDQVSDVCNSPLFKYMDNDYAKLGLSLVVPGGGIKKKSPATPQAKPDGVTATAA
  DEEEDEYSGGLC
• Function: Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
• Reactome Pathway:
  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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Definitive	Biomarker	[1]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[2]
Pick disease	DISP6X50	Strong	Genetic Variation	[2]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[3]

2 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 Gamma-soluble NSF attachment protein (NAPG).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Gamma-soluble NSF attachment protein (NAPG).	[11]

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 Gamma-soluble NSF attachment protein (NAPG).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Gamma-soluble NSF attachment protein (NAPG).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Gamma-soluble NSF attachment protein (NAPG).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gamma-soluble NSF attachment protein (NAPG).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Gamma-soluble NSF attachment protein (NAPG).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gamma-soluble NSF attachment protein (NAPG).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Gamma-soluble NSF attachment protein (NAPG).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Gamma-soluble NSF attachment protein (NAPG).	[13]

References

• [1] Association study on the NAPG gene and bipolar disorder in the Chinese Han population.Neurosci Lett. 2009 Jul 3;457(3):159-62. doi: 10.1016/j.neulet.2009.03.070. Epub 2009 Mar 27.
• [2] Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.Mol Cell. 2013 Oct 24;52(2):264-71. doi: 10.1016/j.molcel.2013.08.041. Epub 2013 Oct 3.
• [3] MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation.J Cell Biochem. 2018 May;119(5):3853-3863. doi: 10.1002/jcb.26464. Epub 2018 Jan 19.
• [4] 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.
• [5] 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.
• [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] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [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] 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.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.