Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ95JJS)

DOT Name E3 ubiquitin-protein ligase HECTD1 (HECTD1)
Synonyms EC 2.3.2.26; E3 ligase for inhibin receptor; EULIR; HECT domain-containing protein 1
Gene Name HECTD1
Related Disease
Acute myocardial infarction ( )
Androgen insensitivity syndrome ( )
Adult glioblastoma ( )
Coronary atherosclerosis ( )
Glioblastoma multiforme ( )
Myocardial ischemia ( )
Metastatic malignant neoplasm ( )
UniProt ID
HECD1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2DK3; 2LC3; 3DKM
EC Number
2.3.2.26
Pfam ID
PF12796 ; PF18410 ; PF00632 ; PF06701 ; PF07738
Sequence
MADVDPDTLLEWLQMGQGDERDMQLIALEQLCMLLLMSDNVDRCFETCPPRTFLPALCKI
FLDESAPDNVLEVTARAITYYLDVSAECTRRIVGVDGAIKALCNRLVVVELNNRTSRDLA
EQCVKVLELICTRESGAVFEAGGLNCVLTFIRDSGHLVHKDTLHSAMAVVSRLCGKMEPQ
DSSLEICVESLSSLLKHEDHQVSDGALRCFASLADRFTRRGVDPAPLAKHGLTEELLSRM
AAAGGTVSGPSSACKPGRSTTGAPSTTADSKLSNQVSTIVSLLSTLCRGSPVVTHDLLRS
ELPDSIESALQGDERCVLDTMRLVDLLLVLLFEGRKALPKSSAGSTGRIPGLRRLDSSGE
RSHRQLIDCIRSKDTDALIDAIDTGAFEVNFMDDVGQTLLNWASAFGTQEMVEFLCERGA
DVNRGQRSSSLHYAACFGRPQVAKTLLRHGANPDLRDEDGKTPLDKARERGHSEVVAILQ
SPGDWMCPVNKGDDKKKKDTNKDEEECNEPKGDPEMAPIYLKRLLPVFAQTFQQTMLPSI
RKASLALIRKMIHFCSEALLKEVCDSDVGHNLPTILVEITATVLDQEDDDDGHLLALQII
RDLVDKGGDIFLDQLARLGVISKVSTLAGPSSDDENEEESKPEKEDEPQEDAKELQQGKP
YHWRDWSIIRGRDCLYIWSDAAALELSNGSNGWFRFILDGKLATMYSSGSPEGGSDSSES
RSEFLEKLQRARGQVKPSTSSQPILSAPGPTKLTVGNWSLTCLKEGEIAIHNSDGQQATI
LKEDLPGFVFESNRGTKHSFTAETSLGSEFVTGWTGKRGRKLKSKLEKTKQKVRTMARDL
YDDHFKAVESMPRGVVVTLRNIATQLESSWELHTNRQCIESENTWRDLMKTALENLIVLL
KDENTISPYEMCSSGLVQALLTVLNNSMDLDMKQDCSQLVERINVFKTAFSENEDDESRP
AVALIRKLIAVLESIERLPLHLYDTPGSTYNLQILTRRLRFRLERAPGETALIDRTGRML
KMEPLATVESLEQYLLKMVAKQWYDFDRSSFVFVRKLREGQNFIFRHQHDFDENGIIYWI
GTNAKTAYEWVNPAAYGLVVVTSSEGRNLPYGRLEDILSRDNSALNCHSNDDKNAWFAID
LGLWVIPSAYTLRHARGYGRSALRNWVFQVSKDGQNWTSLYTHVDDCSLNEPGSTATWPL
DPPKDEKQGWRHVRIKQMGKNASGQTHYLSLSGFELYGTVNGVCEDQLGKAAKEAEANLR
RQRRLVRSQVLKYMVPGARVIRGLDWKWRDQDGSPQGEGTVTGELHNGWIDVTWDAGGSN
SYRMGAEGKFDLKLAPGYDPDTVASPKPVSSTVSGTTQSWSSLVKNNCPDKTSAAAGSSS
RKGSSSSVCSVASSSDISLGSTKTERRSEIVMEHSIVSGADVHEPIVVLSSAENVPQTEV
GSSSSASTSTLTAETGSENAERKLGPDSSVRTPGESSAISMGIVSVSSPDVSSVSELTNK
EAASQRPLSSSASNRLSVSSLLAAGAPMSSSASVPNLSSRETSSLESFVRRVANIARTNA
TNNMNLSRSSSDNNTNTLGRNVMSTATSPLMGAQSFPNLTTPGTTSTVTMSTSSVTSSSN
VATATTVLSVGQSLSNTLTTSLTSTSSESDTGQEAEYSLYDFLDSCRASTLLAELDDDED
LPEPDEEDDENEDDNQEDQEYEEVMILRRPSLQRRAGSRSDVTHHAVTSQLPQVPAGAGS
RPIGEQEEEEYETKGGRRRTWDDDYVLKRQFSALVPAFDPRPGRTNVQQTTDLEIPPPGT
PHSELLEEVECTPSPRLALTLKVTGLGTTREVELPLTNFRSTIFYYVQKLLQLSCNGNVK
SDKLRRIWEPTYTIMYREMKDSDKEKENGKMGCWSIEHVEQYLGTDELPKNDLITYLQKN
ADAAFLRHWKLTGTNKSIRKNRNCSQLIAAYKDFCEHGTKSGLNQGAISTLQSSDILNLT
KEQPQAKAGNGQNSCGVEDVLQLLRILYIVASDPYSRISQEDGDEQPQFTFPPDEFTSKK
ITTKILQQIEEPLALASGALPDWCEQLTSKCPFLIPFETRQLYFTCTAFGASRAIVWLQN
RREATVERTRTTSSVRRDDPGEFRVGRLKHERVKVPRGESLMEWAENVMQIHADRKSVLE
VEFLGEEGTGLGPTLEFYALVAAEFQRTDLGAWLCDDNFPDDESRHVDLGGGLKPPGYYV
QRSCGLFTAPFPQDSDELERITKLFHFLGIFLAKCIQDNRLVDLPISKPFFKLMCMGDIK
SNMSKLIYESRGDRDLHCTESQSEASTEEGHDSLSVGSFEEDSKSEFILDPPKPKPPAWF
NGILTWEDFELVNPHRARFLKEIKDLAIKRRQILSNKGLSEDEKNTKLQELVLKNPSGSG
PPLSIEDLGLNFQFCPSSRIYGFTAVDLKPSGEDEMITMDNAEEYVDLMFDFCMHTGIQK
QMEAFRDGFNKVFPMEKLSSFSHEEVQMILCGNQSPSWAAEDIINYTEPKLGYTRDSPGF
LRFVRVLCGMSSDERKAFLQFTTGCSTLPPGGLANLHPRLTVVRKVDATDASYPSVNTCV
HYLKLPEYSSEEIMRERLLAATMEKGFHLN
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. Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion. Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure. Catalyzes ubiquitination and degradation of ZNF622, an assembly factor for the ribosomal 60S subunit, in hematopoietic cells, thereby promoting hematopoietic stem cell renewal.
Reactome Pathway
Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myocardial infarction DISE3HTG Strong Biomarker [1]
Androgen insensitivity syndrome DISUZBBO Strong Altered Expression [2]
Adult glioblastoma DISVP4LU moderate Biomarker [3]
Coronary atherosclerosis DISKNDYU moderate Biomarker [4]
Glioblastoma multiforme DISK8246 moderate Biomarker [3]
Myocardial ischemia DISFTVXF moderate Biomarker [4]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [12]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [8]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [11]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [13]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of E3 ubiquitin-protein ligase HECTD1 (HECTD1). [16]
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⏷ Show the Full List of 9 Drug(s)

References

1 Integrated network analysis to explore the key mRNAs and lncRNAs in acute myocardial infarction.Math Biosci Eng. 2019 Jul 11;16(6):6426-6437. doi: 10.3934/mbe.2019321.
2 The role of circular RNA HECTD1 expression in disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke.J Clin Lab Anal. 2019 Sep;33(7):e22954. doi: 10.1002/jcla.22954. Epub 2019 Jul 1.
3 Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity.Oncotarget. 2017 Nov 30;8(66):110490-110502. doi: 10.18632/oncotarget.22798. eCollection 2017 Dec 15.
4 circDLPAG4/HECTD1 mediates ischaemia/reperfusion injury in endothelial cells via ER stress.RNA Biol. 2020 Feb;17(2):240-253. doi: 10.1080/15476286.2019.1676114. Epub 2019 Oct 13.
5 The E3Ubiquitin Ligase HectD1 Suppresses EMT and Metastasis by Targeting the+TIP ACF7 for Degradation.Cell Rep. 2018 Jan 23;22(4):1016-1030. doi: 10.1016/j.celrep.2017.12.096. Epub 2018 Jan 28.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 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.
10 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.
11 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.
12 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
13 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.
14 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
15 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
16 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.