Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP5M3R9)

• DOT Name: Ataxin-2-like protein (ATXN2L)
• Synonyms: Ataxin-2 domain protein; Ataxin-2-related protein
• Gene Name: ATXN2L
• Related Disease:
  Advanced cancer
  Gastric cancer
  Multiple sclerosis
  Stomach cancer
  T-cell lymphoma
  Ankylosing spondylitis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  Coeliac disease
  Common variable immunodeficiency
  Coronary atherosclerosis
  Coronary heart disease
  Crohn disease
  Juvenile idiopathic arthritis
  Psoriasis
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Type-1 diabetes
  Ulcerative colitis
  Inflammatory bowel disease
• UniProt ID: ATX2L_HUMAN
• Pfam ID: PF06741 ; PF07145 ; PF14438
• Sequence:
  MLKPQPLQQPSQPQQPPPTQQAVARRPPGGTSPPNGGLPGPLATSAAPPGPPAAASPCLG
  PVAAAGSGLRRGAEGILAPQPPPPQQHQERPGAAAIGSARGQSTGKGPPQSPVFEGVYNN
  SRMLHFLTAVVGSTCDVKVKNGTTYEGIFKTLSSKFELAVDAVHRKASEPAGGPRREDIV
  DTMVFKPSDVMLVHFRNVDFNYATKDKFTDSAIAMNSKVNGEHKEKVLQRWEGGDSNSDD
  YDLESDMSNGWDPNEMFKFNEENYGVKTTYDSSLSSYTVPLEKDNSEEFRQRELRAAQLA
  REIESSPQYRLRIAMENDDGRTEEEKHSAVQRQGSGRESPSLASREGKYIPLPQRVREGP
  RGGVRCSSSRGGRPGLSSLPPRGPHHLDNSSPGPGSEARGINGGPSRMSPKAQRPLRGAK
  TLSSPSNRPSGETSVPPPPAVGRMYPPRSPKSAAPAPISASCPEPPIGSAVPTSSASIPV
  TSSVSDPGVGSISPASPKISLAPTDVKELSTKEPGRTLEPQELARIAGKVPGLQNEQKRF
  QLEELRKFGAQFKLQPSSSPENSLDPFPPRILKEEPKGKEKEVDGLLTSEPMGSPVSSKT
  ESVSDKEDKPPLAPSGGTEGPEQPPPPCPSQTGSPPVGLIKGEDKDEGPVAEQVKKSTLN
  PNAKEFNPTKPLLSVNKSTSTPTSPGPRTHSTPSIPVLTAGQSGLYSPQYISYIPQIHMG
  PAVQAPQMYPYPVSNSVPGQQGKYRGAKGSLPPQRSDQHQPASAPPMMQAAAAAGPPLVA
  ATPYSSYIPYNPQQFPGQPAMMQPMAHYPSQPVFAPMLQSNPRMLTSGSHPQAIVSSSTP
  QYPSAEQPTPQALYATVHQSYPHHATQLHAHQPQPATTPTGSQPQSQHAAPSPVQHQAGQ
  APHLGSGQPQQNLYHPGALTGTPPSLPPGPSAQSPQSSFPQPAAVYAIHHQQLPHGFTNM
  AHVTQAHVQTGITAAPPPHPGAPHPPQVMLLHPPQSHGGPPQGAVPQSGVPALSASTPSP
  YPYIGHPQGEQPGQAPGFPGGADDRIREFSLAGGIWHGRAEGLQVGQDARVLGGE
• Function: Involved in the regulation of stress granule and P-body formation.
• Tissue Specificity: Expressed at high levels in thymus, lymph node, spleen, fetal kidney and adult testis. Constitutively associated with MPL and EPOR in hematopoietic cells.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (hsa05014)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[3]
Ankylosing spondylitis	DISRC6IR	moderate	Genetic Variation	[4]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[4]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[4]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[4]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[4]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[4]
Coronary atherosclerosis	DISKNDYU	moderate	Altered Expression	[5]
Coronary heart disease	DIS5OIP1	moderate	Altered Expression	[5]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[4]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Genetic Variation	[4]
Psoriasis	DIS59VMN	moderate	Genetic Variation	[4]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[4]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[4]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[4]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[4]
Inflammatory bowel disease	DISGN23E	Disputed	Genetic Variation	[6]

3 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 Ataxin-2-like protein (ATXN2L).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ataxin-2-like protein (ATXN2L).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ataxin-2-like protein (ATXN2L).	[19]

14 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 Ataxin-2-like protein (ATXN2L).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ataxin-2-like protein (ATXN2L).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ataxin-2-like protein (ATXN2L).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ataxin-2-like protein (ATXN2L).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ataxin-2-like protein (ATXN2L).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ataxin-2-like protein (ATXN2L).	[13]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Ataxin-2-like protein (ATXN2L).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ataxin-2-like protein (ATXN2L).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ataxin-2-like protein (ATXN2L).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ataxin-2-like protein (ATXN2L).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ataxin-2-like protein (ATXN2L).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ataxin-2-like protein (ATXN2L).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ataxin-2-like protein (ATXN2L).	[21]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Ataxin-2-like protein (ATXN2L).	[22]

References

• [1] ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance.Cell Death Dis. 2019 Feb 20;10(3):173. doi: 10.1038/s41419-019-1362-2.
• [2] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [3] Fusion of the genes ataxin 2 like, ATXN2L, and Janus kinase 2, JAK2, in cutaneous CD4 positive T-cell lymphoma.Oncotarget. 2017 Oct 10;8(61):103775-103784. doi: 10.18632/oncotarget.21790. eCollection 2017 Nov 28.
• [4] Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nat Med. 2015 Sep;21(9):1018-27. doi: 10.1038/nm.3933. Epub 2015 Aug 24.
• [5] Heterogeneity of high density lipoprotein particles.Circulation. 1993 Apr;87(4 Suppl):III22-7.
• [6] Common variants at five new loci associated with early-onset inflammatory bowel disease.Nat Genet. 2009 Dec;41(12):1335-40. doi: 10.1038/ng.489. Epub 2009 Nov 15.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 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.
• [13] 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.
• [14] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [17] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [18] 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.
• [19] 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.
• [20] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [21] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [22] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.