Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZV3BG4)

DOT Name	Ataxin-3-like protein (ATXN3L)
Synonyms	EC 3.4.19.12; Machado-Joseph disease protein 1-like
Gene Name	ATXN3L
Related Disease	Breast cancer ( ) Breast carcinoma ( )
UniProt ID	ATX3L_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3O65
EC Number	3.4.19.12
Pfam ID	PF02099 ; PF16619 ; PF02809
Sequence	MDFIFHEKQEGFLCAQHCLNNLLQGEYFSPVELASIAHQLDEEERMRMAEGGVTSEEYLA FLQQPSENMDDTGFFSIQVISNALKFWGLEIIHFNNPEYQKLGIDPINERSFICNYKQHW FTIRKFGKHWFNLNSLLAGPELISDTCLANFLARLQQQAYSVFVVKGDLPDCEADQLLQI ISVEEMDTPKLNGKKLVKQKEHRVYKTVLEKVSEESDESGTSDQDEEDFQRALELSRQET NREDEHLRSTIELSMQGSSGNTSQDLPKTSCVTPASEQPKKIKEDYFEKHQQEQKQQQQQ SDLPGHSSYLHERPTTSSRAIESDLSDDISEGTVQAAVDTILEIMRKNLKIKGEK
Function	Deubiquitinating enzyme that cleaves both 'Lys-48'-linked and 'Lys-63'-linked poly-ubiquitin chains (in vitro). Acts as a deubiquitinating enzyme for the transcription factor KLF5, playing a role in the regulation of KLF5 stability.
Tissue Specificity	Widely expressed.
KEGG Pathway	Protein processing in endoplasmic reticulum (hsa04141 ) Spinocerebellar ataxia (hsa05017 ) Pathways of neurodegeneration - multiple diseases (hsa05022 )
Reactome Pathway	Josephin domain DUBs (R-HSA-5689877 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Ataxin-3-like protein (ATXN3L) decreases the response to substance of Camptothecin.	[4]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ataxin-3-like protein (ATXN3L).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ataxin-3-like protein (ATXN3L).	[3]
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References

1	Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Krppel-like factor 5 (KLF5).Oncotarget. 2015 Aug 28;6(25):21369-78. doi: 10.18632/oncotarget.4128.
2	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
3	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.
4	ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.