Details of Drug Off-Target (DOT)

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

• DOT Name: GAS2-like protein 1 (GAS2L1)
• Synonyms: GAS2-related protein on chromosome 22; Growth arrest-specific protein 2-like 1
• Gene Name: GAS2L1
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: GA2L1_HUMAN
• Pfam ID: PF00307 ; PF02187
• Sequence:
  MADPVAGIAGSAAKSVRPFRSSEAYVEAMKEDLAEWLNALYGLGLPGGGDGFLTGLATGT
  TLCQHANAVTEAARALAAARPARGVAFQAHSVVPGSFMARDNVATFIGWCRVELGVPEVL
  MFETEDLVLRKNEKSVVLCLLEVARRGARLGLLAPRLVQFEQEIERELRAAPPAPNAPAA
  GEDTTETAPAPGTPARGPRMTPSDLRNLDELVREILGRCTCPDQFPMIKVSEGKYRVGDS
  SLLIFVRVLRSHVMVRVGGGWDTLEHYLDKHDPCRCSSTAHRPPQPRVCTFSPQRVSPTT
  SPRPASPVPGSERRGSRPEMTPVSLRSTKEGPETPPRPRDQLPPHPRSRRYSGDSDSSAS
  SAQSGPLGTRSDDTGTGPRRERPSRRLTTGTPASPRRPPALRSQSRDRLDRGRPRGAPGG
  RGAQLSVPSPARRARSQSREEQAVLLVRRDRDGQHSWVPRGRGSGGSGRSTPQTPRARSP
  AAPRLSRVSSPSPELGTTPASIFRTPLQLDPQQEQQLFRRLEEEFLANARALEAVASVTP
  TGPVPDPARAPDPPAPDSAYCSSSSSSSSLSVLGGKCGQPGDSGRTANGLPGPRSQALSS
  SSDEGSPCPGMGGPLDAPGSPLACTEPSRTWARGRMDTQPDRKPSRIPTPRGPRRPSGPA
  ELGTWHALHSVTPRAEPDSWM
• Function: Involved in the cross-linking of microtubules and microfilaments. Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of GAS2-like protein 1 (GAS2L1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of GAS2-like protein 1 (GAS2L1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GAS2-like protein 1 (GAS2L1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of GAS2-like protein 1 (GAS2L1).	[14]

9 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 GAS2-like protein 1 (GAS2L1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GAS2-like protein 1 (GAS2L1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GAS2-like protein 1 (GAS2L1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GAS2-like protein 1 (GAS2L1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of GAS2-like protein 1 (GAS2L1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of GAS2-like protein 1 (GAS2L1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of GAS2-like protein 1 (GAS2L1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GAS2-like protein 1 (GAS2L1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GAS2-like protein 1 (GAS2L1).	[13]

References

• [1] Discovery of epigenetically silenced genes in acute myeloid leukemias.Leukemia. 2007 May;21(5):1026-34. doi: 10.1038/sj.leu.2404611. Epub 2007 Mar 1.
• [2] 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.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] 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.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] 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.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.
• [14] 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.