Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50JKXQ)

• DOT Name: Growth arrest-specific protein 2 (GAS2)
• Synonyms: GAS-2
• Gene Name: GAS2
• Related Disease:
  Colorectal carcinoma
  Hepatocellular carcinoma
  Neoplasm
  Fanconi's anemia
• UniProt ID: GAS2_HUMAN
• Pfam ID: PF00307 ; PF02187
• Sequence:
  MCTALSPKVRSGPGLSDMHQYSQWLASRHEANLLPMKEDLALWLTNLLGKEITAETFMEK
  LDNGALLCQLAETMQEKFKESMDANKPTKNLPLKKIPCKTSAPSGSFFARDNTANFLSWC
  RDLGVDETCLFESEGLVLHKQPREVCLCLLELGRIAARYGVEPPGLIKLEKEIEQEETLS
  APSPSPSPSSKSSGKKSTGNLLDDAVKRISEDPPCKCPNKFCVERLSQGRYRVGEKILFI
  RMLHNKHVMVRVGGGWETFAGYLLKHDPCRMLQISRVDGKTSPIQSKSPTLKDMNPDNYL
  VVSASYKAKKEIK
• Function: May play a role in apoptosis by acting as a cell death substrate for caspases. Is cleaved during apoptosis and the cleaved form induces dramatic rearrangements of the actin cytoskeleton and potent changes in the shape of the affected cells. May be involved in the membrane ruffling process.
• Tissue Specificity: Ubiquitously expressed with highest levels in liver, lung, and kidney. Not found in spleen.
• Reactome Pathway: Caspase-mediated cleavage of cytoskeletal proteins (R-HSA-264870)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Fanconi's anemia	DISGW6Q8	Disputed	Genetic Variation	[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 Growth arrest-specific protein 2 (GAS2).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Growth arrest-specific protein 2 (GAS2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Growth arrest-specific protein 2 (GAS2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Growth arrest-specific protein 2 (GAS2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Growth arrest-specific protein 2 (GAS2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Growth arrest-specific protein 2 (GAS2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Growth arrest-specific protein 2 (GAS2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Growth arrest-specific protein 2 (GAS2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Growth arrest-specific protein 2 (GAS2).	[10]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Growth arrest-specific protein 2 (GAS2).	[11]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Growth arrest-specific protein 2 (GAS2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Growth arrest-specific protein 2 (GAS2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Growth arrest-specific protein 2 (GAS2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Growth arrest-specific protein 2 (GAS2).	[15]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Growth arrest-specific protein 2 (GAS2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Growth arrest-specific protein 2 (GAS2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Growth arrest-specific protein 2 (GAS2).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Growth arrest-specific protein 2 (GAS2).	[20]

References

• [1] Upregulation of the growth arrest-specific-2 in recurrent colorectal cancers, and its susceptibility to chemotherapy in a model cell system.Biochim Biophys Acta. 2016 Jul;1862(7):1345-53. doi: 10.1016/j.bbadis.2016.04.010. Epub 2016 Apr 13.
• [2] Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis.World J Gastroenterol. 2019 Aug 28;25(32):4715-4726. doi: 10.3748/wjg.v25.i32.4715.
• [3] The Fanconi anemia gene product FANCF is a flexible adaptor protein.J Biol Chem. 2004 Sep 17;279(38):39421-30. doi: 10.1074/jbc.M407034200. Epub 2004 Jul 15.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] Chronic cyclophosphamide exposure alters the profile of rat sperm nuclear matrix proteins. Biol Reprod. 2007 Aug;77(2):303-11. doi: 10.1095/biolreprod.107.060244. Epub 2007 May 2.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] 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.
• [16] 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.
• [17] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [18] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.