Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT93AUOO)

• DOT Name: Atlastin-2 (ATL2)
• Synonyms: EC 3.6.5.-; ADP-ribosylation factor-like protein 6-interacting protein 2; ARL-6-interacting protein 2; Aip-2
• Gene Name: ATL2
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Matthew-Wood syndrome
  T-cell leukaemia
  Acute myelogenous leukaemia
  Tourette syndrome
• UniProt ID: ATLA2_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF02263 ; PF02841
• Sequence:
  MAEGDEAARGQQPHQGLWRRRRTSDPSAAVNHVSSTTSLGENYEDDDLVNSDEVMKKPCP
  VQIVLAHEDDHNFELDEEALEQILLQEHIRDLNIVVVSVAGAFRKGKSFLLDFMLRYMYN
  KDSQSWIGGNNEPLTGFTWRGGCERETTGIQVWNEVFVIDRPNGTKVAVLLMDTQGAFDS
  QSTIKDCATVFALSTMTSSVQVYNLSQNIQEDDLQHLQLFTEYGRLAMEEIYQKPFQTLM
  FLIRDWSYPYEHSYGLEGGKQFLEKRLQVKQNQHEELQNVRKHIHNCFSNLGCFLLPHPG
  LKVATNPSFDGRLKDIDEDFKRELRNLVPLLLAPENLVEKEISGSKVTCRDLVEYFKAYI
  KIYQGEELPHPKSMLQATAEANNLAAVAGARDTYCKSMEQVCGGDKPYIAPSDLERKHLD
  LKEVAIKQFRSVKKMGGDEFCRRYQDQLEAEIEETYANFIKHNDGKNIFYAARTPATLFA
  VMFAMYIISGLTGFIGLNSIAVLCNLVMGLALIFLCTWAYVKYSGEFREIGTVIDQIAET
  LWEQVLKPLGDNLMEENIRQSVTNSIKAGLTDQVSHHARLKTD
• Function: GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis.
• Tissue Specificity: Expressed in peripheral tissues (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[1]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[2]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Tourette syndrome	DISX9D54	No Known	Unknown	[4]

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 Atlastin-2 (ATL2).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Atlastin-2 (ATL2).	[15]

10 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 Atlastin-2 (ATL2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Atlastin-2 (ATL2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Atlastin-2 (ATL2).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Atlastin-2 (ATL2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Atlastin-2 (ATL2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Atlastin-2 (ATL2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Atlastin-2 (ATL2).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Atlastin-2 (ATL2).	[13]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Atlastin-2 (ATL2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Atlastin-2 (ATL2).	[16]

References

• [1] Human leukocyte antigen-class II-negative long-term cultured human T-cell leukemia virus type-I-infected T-cell lines with progressed cytological properties significantly induce superantigen-dependent normal T-cell proliferation.Pathol Int. 2005 May;55(5):264-72. doi: 10.1111/j.1440-1827.2005.01823.x.
• [2] Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma.J Transl Med. 2017 Jun 2;15(1):126. doi: 10.1186/s12967-017-1227-3.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [15] 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.
• [16] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.