Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRIMA50)

• DOT Name: Neuronal vesicle trafficking-associated protein 1 (NSG1)
• Synonyms: Neuron-enriched endosomal protein of 21 kDa; Neuron-specific protein family member 1
• Gene Name: NSG1
• Related Disease:
  Alcohol dependence
  Bone osteosarcoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatitis
  Hepatitis A virus infection
  Hepatitis B virus infection
  Huntington disease
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Osteosarcoma
  Renal cell carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Ulcerative colitis
  Advanced cancer
• UniProt ID: NSG1_HUMAN
• Pfam ID: PF06387
• Sequence:
  MVKLGNNFAEKGTKQPLLEDGFDTIPLMTPLDVNQLQFPPPDKVVVKTKTEYEPDRKKGK
  ARPPQIAEFTVSITEGVTERFKVSVLVLFALAFLTCVVFLVVYKVYKYDRACPDGFVLKN
  TQCIPEGLESYYAEQDSSAREKFYTVINHYNLAKQSITRSVSPWMSVLSEEKLSEQETEA
  AEKSA
• Function: Plays a role in the recycling mechanism in neurons of multiple receptors, including AMPAR, APP and L1CAM and acts at the level of early endosomes to promote sorting of receptors toward a recycling pathway. Regulates sorting and recycling of GRIA2 through interaction with GRIP1 and then contributes to the regulation of synaptic transmission and plasticity by affecting the recycling and targeting of AMPA receptors to the synapse. Is required for faithful sorting of L1CAM to axons by facilitating trafficking from somatodendritic early endosome or the recycling endosome. In an other hand, induces apoptosis via the activation of CASP3 in response to DNA damage.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Hepatitis	DISXXX35	Strong	Altered Expression	[6]
Hepatitis A virus infection	DISUMFQV	Strong	Altered Expression	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[6]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[7]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[8]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[8]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[9]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[10]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[11]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[12]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[13]

13 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 Neuronal vesicle trafficking-associated protein 1 (NSG1).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[24]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[25]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neuronal vesicle trafficking-associated protein 1 (NSG1).	[26]

References

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• [4] Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth.Oncotarget. 2017 Apr 11;8(15):25055-25065. doi: 10.18632/oncotarget.15918.
• [5] Discovery and Validation of a Serologic Autoantibody Panel for Early Diagnosis of Esophageal Squamous Cell Carcinoma.Cancer Epidemiol Biomarkers Prev. 2019 Sep;28(9):1454-1460. doi: 10.1158/1055-9965.EPI-18-1269. Epub 2019 Jun 25.
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• [7] Variable subcellular localization of a neuron-specific protein during NTera 2 differentiation into post-mitotic human neurons.Brain Res Mol Brain Res. 1996 Dec;42(2):202-12. doi: 10.1016/s0169-328x(96)00115-5.
• [8] Comprehensive assessment of P21 polymorphisms and lung cancer risk.J Hum Genet. 2008;53(1):87-95. doi: 10.1007/s10038-007-0222-6. Epub 2007 Nov 28.
• [9] Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.BMC Genet. 2017 Dec 8;18(1):105. doi: 10.1186/s12863-017-0572-9.
• [10] Genetic variation in the 3'-untranslated region of PAK1 influences schizophrenia susceptibility.Exp Ther Med. 2017 Mar;13(3):1101-1108. doi: 10.3892/etm.2017.4039. Epub 2017 Jan 12.
• [11] P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma.J Oral Pathol Med. 2008 Mar;37(3):151-6. doi: 10.1111/j.1600-0714.2007.00604.x.
• [12] Quantification of P21 mRNA in biopsy specimens of colon tissue at different stages of neoplastic transformation.Folia Histochem Cytobiol. 2001;39 Suppl 2:169-70.
• [13] Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer.Drug Deliv. 2017 Nov;24(1):1537-1548. doi: 10.1080/10717544.2017.1386732.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [16] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [17] 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.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [20] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [21] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [22] 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.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [24] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [25] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [26] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.