Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIRWZC0)

• DOT Name: Ganglioside GM2 activator (GM2A)
• Synonyms: Cerebroside sulfate activator protein; GM2-AP; Sphingolipid activator protein 3; SAP-3
• Gene Name: GM2A
• Related Disease: Tay-Sachs disease AB variant
• UniProt ID: SAP3_HUMAN
• PDB ID: 1G13; 1PU5; 1PUB; 1TJJ; 2AF9; 2AG2; 2AG4; 2AG9
• Pfam ID: PF02221
• Sequence:
  MQSLMQAPLLIALGLLLAAPAQAHLKKPSQLSSFSWDNCDEGKDPAVIRSLTLEPDPIIV
  PGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCTDYIGSCTFEHFCDVLDMLIP
  TGEPCPEPLRTYGLPCHCPFKEGTYSLPKSEFVVPDLELPSWLTTGNYRIESVLSSSGKR
  LGCIKIAASLKGI
• Function: The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity. Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3. Has cholesterol transfer activity.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Lysosome (hsa04142)
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tay-Sachs disease AB variant	DISSA3IU	Definitive	Autosomal recessive	[1]

19 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 Ganglioside GM2 activator (GM2A).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ganglioside GM2 activator (GM2A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ganglioside GM2 activator (GM2A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ganglioside GM2 activator (GM2A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ganglioside GM2 activator (GM2A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ganglioside GM2 activator (GM2A).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ganglioside GM2 activator (GM2A).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ganglioside GM2 activator (GM2A).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Ganglioside GM2 activator (GM2A).	[10]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Ganglioside GM2 activator (GM2A).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ganglioside GM2 activator (GM2A).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ganglioside GM2 activator (GM2A).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ganglioside GM2 activator (GM2A).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ganglioside GM2 activator (GM2A).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ganglioside GM2 activator (GM2A).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ganglioside GM2 activator (GM2A).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Ganglioside GM2 activator (GM2A).	[18]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Ganglioside GM2 activator (GM2A).	[19]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Ganglioside GM2 activator (GM2A).	[20]

References

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• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] 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.
• [4] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [10] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [11] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] 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.
• [19] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [20] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.