Details of Drug Off-Target (DOT)

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

• DOT Name: Obg-like ATPase 1 (OLA1)
• Synonyms: DNA damage-regulated overexpressed in cancer 45; DOC45; GTP-binding protein 9
• Gene Name: OLA1
• Related Disease:
  Meningococcal disease
  Hereditary breast ovarian cancer syndrome
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Persistent fetal circulation syndrome
• UniProt ID: OLA1_HUMAN
• PDB ID: 2OHF
• Pfam ID: PF01926 ; PF06071
• Sequence:
  MPPKKGGDGIKPPPIIGRFGTSLKIGIVGLPNVGKSTFFNVLTNSQASAENFPFCTIDPN
  ESRVPVPDERFDFLCQYHKPASKIPAFLNVVDIAGLVKGAHNGQGLGNAFLSHISACDGI
  FHLTRAFEDDDITHVEGSVDPIRDIEIIHEELQLKDEEMIGPIIDKLEKVAVRGGDKKLK
  PEYDIMCKVKSWVIDQKKPVRFYHDWNDKEIEVLNKHLFLTSKPMVYLVNLSEKDYIRKK
  NKWLIKIKEWVDKYDPGALVIPFSGALELKLQELSAEERQKYLEANMTQSALPKIIKAGF
  AALQLEYFFTAGPDEVRAWTIRKGTKAPQAAGKIHTDFEKGFIMAEVMKYEDFKEEGSEN
  AVKAAGKYRQQGRNYIVEDGDIIFFKFNTPQQPKKK
• Function: Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.
• Tissue Specificity: Expressed in all tissues tested but its expression is more abundant in testis, liver, lung, and brain. Overexpressed in several malignancies, including cancers of the colon, rectum, ovary, lung, stomach, and uterus.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meningococcal disease	DISGDM2Z	Strong	Genetic Variation	[1]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[2]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[3]
Lung cancer	DISCM4YA	Limited	Altered Expression	[3]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[3]
Persistent fetal circulation syndrome	DISSDYEX	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Obg-like ATPase 1 (OLA1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Obg-like ATPase 1 (OLA1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Obg-like ATPase 1 (OLA1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Obg-like ATPase 1 (OLA1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Obg-like ATPase 1 (OLA1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Obg-like ATPase 1 (OLA1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Obg-like ATPase 1 (OLA1).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Obg-like ATPase 1 (OLA1).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Obg-like ATPase 1 (OLA1).	[13]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Obg-like ATPase 1 (OLA1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Obg-like ATPase 1 (OLA1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Obg-like ATPase 1 (OLA1).	[18]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Obg-like ATPase 1 (OLA1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Obg-like ATPase 1 (OLA1).	[16]

References

• [1] Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
• [2] OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer.Breast Cancer. 2017 Mar;24(2):336-340. doi: 10.1007/s12282-016-0709-0. Epub 2016 Jun 6.
• [3] OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3/snail/E-cadherin signaling.Oncotarget. 2016 Mar 1;7(9):10402-13. doi: 10.18632/oncotarget.7224.
• [4] Decreased OLA1 (Obg-Like ATPase-1) Expression Drives Ubiquitin-Proteasome Pathways to Downregulate Mitochondrial SOD2 (Superoxide Dismutase) in Persistent Pulmonary Hypertension of the Newborn.Hypertension. 2019 Oct;74(4):957-966. doi: 10.1161/HYPERTENSIONAHA.119.13430. Epub 2019 Sep 3.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [15] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [16] 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.
• [17] 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.
• [18] 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.