Details of Drug Off-Target (DOT)

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

DOT Name Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2)
Synonyms EC 2.3.2.26; HECT domain-containing protein 2; HECT-type E3 ubiquitin transferase HECTD2
Gene Name HECTD2
Related Disease
Alzheimer disease ( )
Creutzfeldt Jacob disease ( )
Castration-resistant prostate carcinoma ( )
UniProt ID
HECD2_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
Sequence
MSEAVRVPSPATPLVVAAPAPEERKGKESEREKLPPIVSAGAGATAGLDRGAKGQISTFS
SFISAVSPKKEAAENRSSPAHLVFPNIKNVREPPPICLDVRQKQRTSMDASSSEMKAPVL
PEPILPIQPKTVKDFQEDVEKVKSSGDWKAVHDFYLTTFDSFPELNAAFKKDATASFNTI
EDSGINAKFVNAVYDTLLNTPQDVQKTVLKGIINSLLREWKGPRTKDDLRAYFILLQNPQ
FNNTSTYVIYAHLLRQIATLVEADHHFLVHWFKKLSQKRFKQLVERLLQFISLRLFPAKP
EEFPPITKCSWWIPSAAKVLALLNTANNLVHPPLIPYTDFYNSTLDHIDLMEEYHTWQNF
GNSHRFSFCQYPFVISVAAKKIIIQRDSEQQMINIARQSLVDKVSRRQRPDMNILFLNMK
VRRTHLVSDSLDELTRKRADLKKKLKVTFVGEAGLDMGGLTKEWFLLLIRQIFHPDYGMF
TYHKDSHCHWFSSFKCDNYSEFRLVGILMGLAVYNSITLDIRFPPCCYKKLLSPPIIPSD
QNIPVGICNVTVDDLCQIMPELAHGLSELLSHEGNVEEDFYSTFQVFQEEFGIIKSYNLK
PGGDKISVTNQNRKEYVQLYTDFLLNKSIYKQFAAFYYGFHSVCASNALMLLRPEEVEIL
VCGSPDLDMHALQRSTQYDGYAKTDLTIKYFWDVVLGFPLDLQKKLLHFTTGSDRVPVGG
MADLNFKISKNETSTNCLPVAHTCFNQLCLPPYKSKKDLKQKLIIGISNSEGFGLE
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; (Microbial infection) Catalyzes ubiquitination of Botulinum neurotoxin A light chain (LC) of C.botulinum neurotoxin type A (BoNT/A).
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
Alzheimer disease DISF8S70 Strong Biomarker [1]
Creutzfeldt Jacob disease DISCB6RX Strong Biomarker [2]
Castration-resistant prostate carcinoma DISVGAE6 Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [4]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [8]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [9]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [12]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of Probable E3 ubiquitin-protein ligase HECTD2 (HECTD2). [8]
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⏷ Show the Full List of 9 Drug(s)

References

1 HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q.BMC Med Genet. 2009 Sep 15;10:90. doi: 10.1186/1471-2350-10-90.
2 Absence of association between two HECTD2 polymorphisms and sporadic Creutzfeldt-Jakob disease.Dement Geriatr Cogn Disord. 2011;31(2):146-51. doi: 10.1159/000324133. Epub 2011 Feb 17.
3 MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A.Oncogene. 2014 May 22;33(21):2790-800. doi: 10.1038/onc.2013.230. Epub 2013 Jun 17.
4 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.
5 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
10 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 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.