Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYWZ4EM)

DOT Name DIS3-like exonuclease 1 (DIS3L)
Synonyms EC 3.1.13.1
Gene Name DIS3L
Related Disease
Medulloblastoma ( )
UniProt ID
DI3L1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.13.1
Pfam ID
PF17849 ; PF00773 ; PF17216 ; PF17215
Sequence
MLQKREKVLLLRTFQGRTLRIVREHYLRPCVPCHSPLCPQPAACSHDGKLLSSDVTHYVI
PDWKVVQDYLEILEFPELKGIIFMQTACQAVQHQRGRRQYNKLRNLLKDARHDCILFANE
FQQCCYLPRERGESMEKWQTRSIYNAAVWYYHHCQDRMPIVMVTEDEEAIQQYGSETEGV
FVITFKNYLDNFWPDLKAAHELCDSILQSRRERENESQESHGKEYPEHLPLEVLEAGIKS
GRYIQGILNVNKHRAQIEAFVRLQGASSKDSDLVSDILIHGMKARNRSIHGDVVVVELLP
KNEWKGRTVALCENDCDDKASGESPSEPMPTGRVVGILQKNWRDYVVTFPSKEEVQSQGK
NAQKILVTPWDYRIPKIRISTQQAETLQDFRVVVRIDSWESTSVYPNGHFVRVLGRIGDL
EGEIATILVENSISVIPFSEAQMCEMPVNTPESPWKVSPEEEQKRKDLRKSHLVFSIDPK
GCEDVDDTLSVRTLNNGNLELGVHIADVTHFVAPNSYIDIEARTRATTYYLADRRYDMLP
SVLSADLCSLLGGVDRYAVSIMWELDKASYEIKKVWYGRTIIRSAYKLFYEAAQELLDGN
LSVVDDIPEFKDLDEKSRQAKLEELVWAIGKLTDIARHVRAKRDGCGALELEGVEVCVQL
DDKKNIHDLIPKQPLEVHETVAECMILANHWVAKKIWESFPHQALLRQHPPPHQEFFSEL
RECAKAKGFFIDTRSNKTLADSLDNANDPHDPIVNRLLRSMATQAMSNALYFSTGSCAEE
EFHHYGLALDKYTHFTSPIRRYSDIVVHRLLMAAISKDKKMEIKGNLFSNKDLEELCRHI
NNRNQAAQHSQKQSTELFQCMYFKDKDPATEERCISDGVIYSIRTNGVLLFIPRFGIKGA
AYLKNKDGLVISCGPDSCSEWKPGSLQRFQNKITSTTTDGESVTFHLFDHVTVRISIQAS
RCHSDTIRLEIISNKPYKIPNTELIHQSSPLLKSELVKEVTKSVEEAQLAQEVKVNIIQE
EYQEYRQTKGRSLYTLLEEIRDLALLDVSNNYGI
Function
Catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA.
KEGG Pathway
R. degradation (hsa03018 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Medulloblastoma DISZD2ZL Strong Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 DIS3-like exonuclease 1 (DIS3L). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of DIS3-like exonuclease 1 (DIS3L). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DIS3-like exonuclease 1 (DIS3L). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DIS3-like exonuclease 1 (DIS3L). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DIS3-like exonuclease 1 (DIS3L). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DIS3-like exonuclease 1 (DIS3L). [7]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of DIS3-like exonuclease 1 (DIS3L). [8]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of DIS3-like exonuclease 1 (DIS3L). [9]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of DIS3-like exonuclease 1 (DIS3L). [11]
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⏷ Show the Full List of 9 Drug(s)
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 affects the methylation of DIS3-like exonuclease 1 (DIS3L). [10]
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References

1 Zfx facilitates tumorigenesis caused by activation of the Hedgehog pathway.Cancer Res. 2014 Oct 15;74(20):5914-24. doi: 10.1158/0008-5472.CAN-14-0834. Epub 2014 Aug 27.
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 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.
5 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.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 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.
11 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.