Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIW2HTX)

DOT Name E3 ubiquitin-protein ligase listerin (LTN1)
Synonyms EC 2.3.2.27; RING finger protein 160; RING-type E3 ubiquitin transferase listerin; Zinc finger protein 294
Gene Name LTN1
Related Disease
Bipolar disorder ( )
Schizoaffective disorder ( )
Schizophrenia ( )
UniProt ID
LTN1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3J92
EC Number
2.3.2.27
Sequence
MGGKNKQRTKGNLRPSNSGRAAELLAKEQGTVPGFIGFGTSQSDLGYVPAIQGAEEIDSL
VDSDFRMVLRKLSKKDVTTKLKAMQEFGTMCTERDTETVKGVLPYWPRIFCKISLDHDRR
VREATQQAFEKLILKVKKQLAPYLKSLMGYWLMAQCDTYTPAAFAAKDAFEAAFPPSKQP
EAIAFCKDEITSVLQDHLIKETPDTLSDPQTVPEEEREAKFYRVVTCSLLALKRLLCLLP
DNELDSLEEKFKSLLSQNKFWKYGKHSVPQIRSAYFELVSALCQRIPQLMKEEASKVSPS
VLLSIDDSDPIVCPALWEAVLYTLTTIEDCWLHVNAKKSVFPKLSTVIREGGRGLATVIY
PYLLPFISKLPQSITNPKLDFFKNFLTSLVAGLSTERTKTSSLESSAVISAFFECLRFIM
QQNLGEEEIEQMLVNDQLIPFIDAVLKDPGLQHGQLFNHLAETLSSWEAKADTEKDEKTA
HNLENVLIHFWERLSEICVAKISEPEADVESVLGVSNLLQVLQKPKSSLKSSKKKNGKVR
FADEILESNKENEKCVSSEGEKIEGWELTTEPSLTHNSSGLLSPLRKKPLEDLVCKLADI
SINYVNERKSEQHLRFLSTLLDSFSSSRVFKMLLGDEKQSIVQAKPLEIAKLVQKNPAVQ
FLYQKLIGWLNEDQRKDFGFLVDILYSALRCCDNDMERKKVLDDLTKVDLKWNSLLKIIE
KACPSSDKHALVTPWLKGDILGEKLVNLADCLCNEDLESRVSSESHFSERWTLLSLVLSQ
HVKNDYLIGDVYVERIIVRLHETLFKTKKLSEAESSDSSVSFICDVAYNYFSSAKGCLLM
PSSEDLLLTLFQLCAQSKEKTHLPDFLICKLKNTWLSGVNLLVHQTDSSYKESTFLHLSA
LWLKNQVQASSLDINSLQVLLSAVDDLLNTLLESEDSYLMGVYIGSVMPNDSEWEKMRQS
LPMQWLHRPLLEGRLSLNYECFKTDFKEQDIKTLPSHLCTSALLSKMVLIALRKETVLEN
NELEKIIAELLYSLQWCEELDNPPIFLIGFCEILQKMNITYDNLRVLGNTSGLLQLLFNR
SREHGTLWSLIIAKLILSRSISSDEVKPHYKRKESFFPLTEGNLHTIQSLCPFLSKEEKK
EFSAQCIPALLGWTKKDLCSTNGGFGHLAIFNSCLQTKSIDDGELLHGILKIIISWKKEH
EDIFLFSCNLSEASPEVLGVNIEIIRFLSLFLKYCSSPLAESEWDFIMCSMLAWLETTSE
NQALYSIPLVQLFACVSCDLACDLSAFFDSTTLDTIGNLPVNLISEWKEFFSQGIHSLLL
PILVTVTGENKDVSETSFQNAMLKPMCETLTYISKEQLLSHKLPARLVADQKTNLPEYLQ
TLLNTLAPLLLFRARPVQIAVYHMLYKLMPELPQYDQDNLKSYGDEEEEPALSPPAALMS
LLSIQEDLLENVLGCIPVGQIVTIKPLSEDFCYVLGYLLTWKLILTFFKAASSQLRALYS
MYLRKTKSLNKLLYHLFRLMPENPTYAETAVEVPNKDPKTFFTEELQLSIRETTMLPYHI
PHLACSVYHMTLKDLPAMVRLWWNSSEKRVFNIVDRFTSKYVSSVLSFQEISSVQTSTQL
FNGMTVKARATTREVMATYTIEDIVIELIIQLPSNYPLGSIIVESGKRVGVAVQQWRNWM
LQLSTYLTHQNGSIMEGLALWKNNVDKRFEGVEDCMICFSVIHGFNYSLPKKACRTCKKK
FHSACLYKWFTSSNKSTCPLCRETFF
Function
E3 ubiquitin-protein ligase component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation. Within the RQC complex, LTN1 is recruited to stalled 60S ribosomal subunits by NEMF and mediates ubiquitination of stalled nascent chains. Ubiquitination leads to VCP/p97 recruitment for extraction and degradation of the incomplete translation product.
Reactome Pathway
Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 moderate Genetic Variation [1]
Schizoaffective disorder DISLBW6B moderate Genetic Variation [1]
Schizophrenia DISSRV2N moderate Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 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 E3 ubiquitin-protein ligase listerin (LTN1). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [5]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [6]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [7]
Marinol DM70IK5 Approved Marinol increases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [8]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [5]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [5]
Ifosfamide DMCT3I8 Approved Ifosfamide decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [5]
Clodronate DM9Y6X7 Approved Clodronate decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [11]
Celastrol DMWQIJX Preclinical Celastrol decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [14]
Myricetin DMTV4L0 Investigative Myricetin decreases the expression of E3 ubiquitin-protein ligase listerin (LTN1). [15]
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⏷ Show the Full List of 15 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 decreases the methylation of E3 ubiquitin-protein ligase listerin (LTN1). [9]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of E3 ubiquitin-protein ligase listerin (LTN1). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of E3 ubiquitin-protein ligase listerin (LTN1). [13]
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References

1 Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 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.
5 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
6 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.
7 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
8 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
9 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.
10 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.
11 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.
12 Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
13 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.
14 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.
15 Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer HCT-15?cells. Food Chem Toxicol. 2018 Jun;116(Pt B):315-322. doi: 10.1016/j.fct.2018.04.053. Epub 2018 Apr 24.