Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3QNM39)

DOT Name Arginyl-tRNA--protein transferase 1 (ATE1)
Synonyms Arginyltransferase 1; R-transferase 1; EC 2.3.2.8; Arginine-tRNA--protein transferase 1
Gene Name ATE1
Related Disease
Advanced cancer ( )
Breast carcinoma ( )
Neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Congenital heart disease ( )
Neuroblastoma ( )
UniProt ID
ATE1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.8
Pfam ID
PF04377 ; PF04376
Sequence
MAFWAGGSPSVVDYFPSEDFYRCGYCKNESGSRSNGMWAHSMTVQDYQDLIDRGWRRSGK
YVYKPVMNQTCCPQYTIRCRPLQFQPSKSHKKVLKKMLKFLAKGEVPKGSCEDEPMDSTM
DDAVAGDFALINKLDIQCDLKTLSDDIKESLESEGKNSKKEEPQELLQSQDFVGEKLGSG
EPSHSVKVHTVPKPGKGADLSKPPCRKAKEIRKERKRLKLMQQNPAGELEGFQAQGHPPS
LFPPKAKSNQPKSLEDLIFESLPENASHKLEVRVVRSSPPSSQFKATLLESYQVYKRYQM
VIHKNPPDTPTESQFTRFLCSSPLEAETPPNGPDCGYGSFHQQYWLDGKIIAVGVIDILP
NCVSSVYLYYDPDYSFLSLGVYSALREIAFTRQLHEKTSQLSYYYMGFYIHSCPKMKYKG
QYRPSDLLCPETYVWVPIEQCLPSLENSKYCRFNQDPEAVDEDRSTEPDRLQVFHKRAIM
PYGVYKKQQKDPSEEAAVLQYASLVGQKCSERMLLFRN
Function
Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein. This arginylation is required for degradation of the protein via the ubiquitin pathway. Does not arginylate cysteine residues.
BioCyc Pathway
MetaCyc:HS03017-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Altered Expression [1]
Prostate cancer DISF190Y Strong Biomarker [1]
Prostate carcinoma DISMJPLE Strong Biomarker [1]
Congenital heart disease DISQBA23 Disputed Autosomal recessive [3]
Neuroblastoma DISVZBI4 Limited Biomarker [4]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Arginyl-tRNA--protein transferase 1 (ATE1). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [8]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [10]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [17]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Arginyl-tRNA--protein transferase 1 (ATE1). [18]
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⏷ Show the Full List of 11 Drug(s)
3 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 increases the methylation of Arginyl-tRNA--protein transferase 1 (ATE1). [12]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Arginyl-tRNA--protein transferase 1 (ATE1). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Arginyl-tRNA--protein transferase 1 (ATE1). [16]
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References

1 Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis.Oncogene. 2019 Feb;38(6):838-851. doi: 10.1038/s41388-018-0462-2. Epub 2018 Sep 3.
2 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Beta-amyloid induces apoptosis of neuronal cells by inhibition of the Arg/N-end rule pathway proteolytic activity.Aging (Albany NY). 2019 Aug 24;11(16):6134-6152. doi: 10.18632/aging.102177. Epub 2019 Aug 24.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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 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.
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 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
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 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.
14 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
15 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.
16 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.
17 Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.