Details of Drug Off-Target (DOT)

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

DOT Name Ataxin-7-like protein 3B (ATXN7L3B)
Gene Name ATXN7L3B
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Cerebellar ataxia ( )
Nervous system disease ( )
UniProt ID
A7L3B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEEISLANLDTNKLEAIAQEIYVDLIEDSCLGFCFEVHRAVKCGYFYLEFAETGSVKDFG
IQPVEDKGACRLPLCSLPGEPGNGPDQQLQRSPPEFQ
Function
By binding to ENY2, interferes with the nuclear functions of the deubiquitinase (DUB) module of the SAGA complex which consists of ENY2, ATXN7, ATXN7L3 and the histone deubiquitinating component USP22. Affects USP22 DUB activity toward histones indirectly by changing the subcellular distribution of ENY2 and altering ENY2 availability for ATXN7L3 interaction. Regulates H2B monoubiquitination (H2Bub1) levels through cytoplasmic sequestration of ENY2 resulting in loss of nuclear ENY2-ATXN7L3 association which destabilizes ATXN7L3. Affects protein expression levels of ENY2 and ATXN7L3.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Cerebellar ataxia DIS9IRAV Strong Biomarker [2]
Nervous system disease DISJ7GGT Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 Ataxin-7-like protein 3B (ATXN7L3B). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [5]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [8]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [9]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Ataxin-7-like protein 3B (ATXN7L3B). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [10]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [11]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [12]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [13]
Resorcinol DMM37C0 Investigative Resorcinol increases the expression of Ataxin-7-like protein 3B (ATXN7L3B). [14]
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⏷ Show the Full List of 13 Drug(s)

References

1 Cytoplasmic ATXN7L3B Interferes with Nuclear Functions of the SAGA Deubiquitinase Module.Mol Cell Biol. 2016 Oct 28;36(22):2855-2866. doi: 10.1128/MCB.00193-16. Print 2016 Nov 15.
2 Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):1255-7. doi: 10.1136/jnnp-2012-304555. Epub 2013 Mar 9.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
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 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.
8 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.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
11 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
12 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
13 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
14 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.