Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWMKYD9)

DOT Name Probable E3 ubiquitin-protein ligase HERC3 (HERC3)
Synonyms EC 2.3.2.26; HECT domain and RCC1-like domain-containing protein 3; HECT-type E3 ubiquitin transferase HERC3
Gene Name HERC3
Related Disease
Invasive breast carcinoma ( )
Liver cancer ( )
UniProt ID
HERC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.26
Pfam ID
PF00632 ; PF00415
Sequence
MLCWGYWSLGQPGISTNLQGIVAEPQVCGFISDRSVKEVACGGNHSVFLLEDGEVYTCGL
NTKGQLGHEREGNKPEQIGALADQHIIHVACGESHSLALSDRGQLFSWGAGSDGQLGLMT
TEDSVAVPRLIQKLNQQTILQVSCGNWHCLALAADGQFFTWGKNSHGQLGLGKEFPSQAS
PQRVRSLEGIPLAQVAAGGAHSFALSLSGAVFGWGMNNAGQLGLSDEKDRESPCHVKLLR
TQKVVYISCGEEHTAVLTKSGGVFTFGAGSCGQLGHDSMNDEVNPRRVLELMGSEVTQIA
CGRQHTLAFVPSSGLIYAFGCGARGQLGTGHTCNVKCPSPVKGYWAAHSGQLSARADRFK
YHIVKQIFSGGDQTFVLCSKYENYSPAVDFRTMNQAHYTSLINDETIAVWRQKLSEHNNA
NTINGVVQILSSAACWNGSFLEKKIDEHFKTSPKIPGIDLNSTRVLFEKLMNSQHSMILE
QILNSFESCLIPQLSSSPPDVEAMRIYLILPEFPLLQDSKYYITLTIPLAMAILRLDTNP
SKVLDNWWSQVCPKYFMKLVNLYKGAVLYLLRGRKTFLIPVLFNNYITAALKLLEKLYKV
NLKVKHVEYDTFYIPEISNLVDIQEDYLMWFLHQAGMKARPSIIQDTVTLCSYPFIFDAQ
AKTKMLQTDAELQMQVAVNGANLQNVFMLLTLEPLLARSPFLVLHVRRNNLVGDALRELS
IHSDIDLKKPLKVIFDGEEAVDAGGVTKEFFLLLLKELLNPIYGMFTYYQDSNLLWFSDT
CFVEHNWFHLIGITCGLAIYNSTVVDLHFPLALYKKLLNVKPGLEDLKELSPTEGRSLQE
LLDYPGEDVEETFCLNFTICRESYGVIEQKKLIPGGDNVTVCKDNRQEFVDAYVNYVFQI
SVHEWYTAFSSGFLKVCGGKVLELFQPSELRAMMVGNSNYNWEELEETAIYKGDYSATHP
TVKLFWETFHEFPLEKKKKFLLFLTGSDRIPIYGMASLQIVIQSTASGEEYLPVAHTCYN
LLDLPKYSSKEILSARLTQALDNYEGFSLA
Function E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
KEGG Pathway
Ubiquitin mediated proteolysis (hsa04120 )
Reactome Pathway
Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Invasive breast carcinoma DISANYTW Definitive Altered Expression [1]
Liver cancer DISDE4BI Strong Biomarker [2]
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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 increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [3]
Tretinoin DM49DUI Approved Tretinoin affects the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [9]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [10]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [6]
Fenofibrate DMFKXDY Approved Fenofibrate increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [6]
Ifosfamide DMCT3I8 Approved Ifosfamide decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [6]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [11]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [14]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [15]
EPZ-004777 DMLN4V5 Investigative EPZ-004777 increases the expression of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [16]
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⏷ Show the Full List of 15 Drug(s)
2 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 Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Probable E3 ubiquitin-protein ligase HERC3 (HERC3). [13]
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References

1 Np63 down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence.Cell Death Differ. 2018 Dec;25(12):2118-2129. doi: 10.1038/s41418-018-0132-5. Epub 2018 Jun 7.
2 Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
3 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.
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 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 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.
7 Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
8 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.
9 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
11 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
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 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 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
15 Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
16 Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nat Commun. 2020 Aug 19;11(1):4153. doi: 10.1038/s41467-020-18013-7.