Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ17ZDT)

DOT Name Protein LTO1 homolog (LTO1)
Synonyms Oral cancer-overexpressed protein 1; Tumor-amplified and overexpressed sequence 1
Gene Name LTO1
Related Disease
Cervical cancer ( )
Cervical carcinoma ( )
Esophageal squamous cell carcinoma ( )
Advanced cancer ( )
Inflammatory bowel disease ( )
Irritable bowel syndrome ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Oral cancer ( )
Squamous cell carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Leukoplakia ( )
UniProt ID
LTO1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF09811
Sequence
MAGSQDIFDAIVMADERFHGEGYREGYEEGSSLGVMEGRQHGTLHGAKIGSEIGCYQGFA
FAWKCLLHSCTTEKDSRKMKVLESLIGMIQKFPYDDPTYDKLHEDLDKIRGKFKQFCSLL
NVQPDFKISAEGSGLSF
Function
The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery. May be required for biogenesis of the large ribosomal subunit and initiation of translation. May play a role in the regulation of proline metabolism and ROS production.
Tissue Specificity Widely expressed. Highly expressed in placenta, kidney and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cervical cancer DISFSHPF Definitive Biomarker [1]
Cervical carcinoma DIST4S00 Definitive Biomarker [1]
Esophageal squamous cell carcinoma DIS5N2GV Definitive Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Inflammatory bowel disease DISGN23E Strong Biomarker [4]
Irritable bowel syndrome DIS27206 Strong Biomarker [4]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [5]
Neoplasm DISZKGEW Strong Altered Expression [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [6]
Oral cancer DISLD42D Strong Biomarker [3]
Squamous cell carcinoma DISQVIFL Strong Biomarker [7]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W moderate Genetic Variation [8]
Liver cancer DISDE4BI moderate Genetic Variation [8]
Leukoplakia DIST3QD3 Limited Biomarker [9]
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⏷ Show the Full List of 14 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Protein LTO1 homolog (LTO1). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Protein LTO1 homolog (LTO1). [12]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein LTO1 homolog (LTO1). [13]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Protein LTO1 homolog (LTO1). [11]
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References

1 Oral cancer overexpressed 1 (ORAOV1) regulates cell cycle and apoptosis in cervical cancer HeLa cells.Mol Cancer. 2010 Jan 28;9:20. doi: 10.1186/1476-4598-9-20.
2 Frequent amplification of ORAOV1 gene in esophageal squamous cell cancer promotes an aggressive phenotype via proline metabolism and ROS production.Oncotarget. 2014 May 30;5(10):2962-73. doi: 10.18632/oncotarget.1561.
3 The function of ORAOV1/LTO1, a gene that is overexpressed frequently in cancer: essential roles in the function and biogenesis of the ribosome.Oncogene. 2014 Jan 23;33(4):484-94. doi: 10.1038/onc.2012.604. Epub 2013 Jan 14.
4 VP2 of Infectious Bursal Disease Virus Induces Apoptosis via Triggering Oral Cancer Overexpressed 1 (ORAOV1) Protein Degradation.Front Microbiol. 2017 Jul 19;8:1351. doi: 10.3389/fmicb.2017.01351. eCollection 2017.
5 ORAOV1 is a probable target within the 11q13.3 amplicon in lymph node metastases from gastric adenocarcinoma.Int J Mol Med. 2012 Jan;29(1):81-7. doi: 10.3892/ijmm.2011.811. Epub 2011 Oct 11.
6 Genetic instability and recurrent MYC amplification in ALK-translocated NSCLC: a central role of TP53 mutations.J Pathol. 2018 Sep;246(1):67-76. doi: 10.1002/path.5110. Epub 2018 Jul 31.
7 ORAOV1 is amplified in oral squamous cell carcinoma.J Oral Pathol Med. 2012 Jan;41(1):54-60. doi: 10.1111/j.1600-0714.2011.01053.x. Epub 2011 May 28.
8 Comparative genomics on mammalian Fgf3-Fgf4 locus.Int J Oncol. 2005 Jul;27(1):281-5.
9 Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features.Oral Oncol. 2007 May;43(5):508-14. doi: 10.1016/j.oraloncology.2006.05.008. Epub 2006 Sep 26.
10 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.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
12 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.
13 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.