Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7G9PQE)

DOT Name Probable E3 ubiquitin-protein ligase HERC6 (HERC6)
Synonyms EC 2.3.2.26; HECT domain and RCC1-like domain-containing protein 6; HECT-type E3 ubiquitin transferase HERC6
Gene Name HERC6
Related Disease
Epileptic encephalopathy ( )
Influenza ( )
X-linked Opitz G/BBB syndrome ( )
UniProt ID
HERC6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5W87
EC Number
2.3.2.26
Pfam ID
PF00632 ; PF00415 ; PF13540
Sequence
MYFCWGADSRELQRRRTAGSPGAELLQAASGERHSLLLLTNHRVLSCGDNSRGQLGRRGA
QRGELPEPIQALETLIVDLVSCGKEHSLAVCHKGRVFAWGAGSEGQLGIGEFKEISFTPK
KIMTLNDIKIIQVSCGHYHSLALSKDSQVFSWGKNSHGQLGLGKEFPSQASPQRVRSLEG
IPLAQVAAGGAHSFALSLCGTSFGWGSNSAGQLALSGRNVPVQSNKPLSVGALKNLGVVY
ISCGDAHTAVLTQDGKVFTFGDNRSGQLGYSPTPEKRGPQLVERIDGLVSQIDCGSYHTL
AYVHTTGQVVSFGHGPSDTSKPTHPEALTENFDISCLISAEDFVDVQVKHIFAGTYANFV
TTHQDTSSTRAPGKTLPEISRISQSMAEKWIAVKRRSTEHEMAKSEIRMIFSSPACLTAS
FLKKRGTGETTSIDVDLEMARDTFKKLTKKEWISSMITTCLEDDLLRALPCHSPHQEALS
VFLLLPECPVMHDSKNWKNLVVPFAKAVCEMSKQSLQVLKKCWAFLQESSLNPLIQMLKA
AIISQLLHQTKTEQDHCNVKALLGMMKELHKVNKANCRLPENTFNINELSNLLNFYIDRG
RQLFRDNHLIPAETPSPVIFSDFPFIFNSLSKIKLLQADSHIKMQMSEKKAYMLMHETIL
QKKDEFPPSPRFILRVRRSRLVKDALRQLSQAEATDFCKVLVVEFINEICPESGGVSSEF
FHCMFEEMTKPEYGMFMYPEMGSCMWFPAKPKPEKKRYFLFGMLCGLSLFNLNVANLPFP
LALYKKLLDQKPSLEDLKELSPRLGKSLQEVLDDAADDIGDALCIRFSIHWDQNDVDLIP
NGISIPVDQTNKRDYVSKYIDYIFNVSVKAVYEEFQRGFYRVCEKEILRHFYPEELMTAI
IGNTDYDWKQFEQNSKYEQGYQKSHPTIQLFWKAFHKLTLDEKKKFLFFLTGRDRLHARG
IQKMEIVFRCPETFSERDHPTSITCHNILSLPKYSTMERMEEALQVAINNNRGFVSPMLT
QS
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.
Tissue Specificity Detected in brain, heart, placenta and testis.
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
Epileptic encephalopathy DISZOCA3 Strong Biomarker [1]
Influenza DIS3PNU3 Strong Biomarker [2]
X-linked Opitz G/BBB syndrome DISQ14EC Strong Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
19 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 Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [8]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [9]
Triclosan DMZUR4N Approved Triclosan increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [10]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [11]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [11]
Diclofenac DMPIHLS Approved Diclofenac decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [11]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [12]
Prednisolone DMQ8FR2 Approved Prednisolone decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [11]
Methylprednisolone DM4BDON Approved Methylprednisolone decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [13]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [17]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [18]
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⏷ Show the Full List of 19 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 decreases the methylation of Probable E3 ubiquitin-protein ligase HERC6 (HERC6). [16]
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References

1 Heterogeneous expression and biological function of SOX18 in osteosaroma.J Cell Biochem. 2018 May;119(5):4184-4192. doi: 10.1002/jcb.26635. Epub 2018 Jan 22.
2 A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
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 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
6 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
7 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.
8 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
9 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.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
12 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 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.
15 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
16 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.
17 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.
18 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.