Details of Drug Off-Target (DOT)

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

DOT Name Dynactin subunit 3 (DCTN3)
Synonyms Dynactin complex subunit 22 kDa subunit; p22
Gene Name DCTN3
Related Disease
Tuberculosis ( )
Arthritis ( )
Breast carcinoma ( )
Chronic granulomatous disease ( )
Estrogen-receptor positive breast cancer ( )
facioscapulohumeral muscular dystrophy ( )
Frontometaphyseal dysplasia 1 ( )
Head-neck squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Lyme disease ( )
Medullary thyroid gland carcinoma ( )
Neoplasm ( )
Obstructive sleep apnea ( )
Oral cancer ( )
Oral cavity carcinoma ( )
Polycystic kidney disease ( )
Primary cutaneous peripheral T-cell lymphoma not otherwise specified ( )
Syphilis ( )
Advanced cancer ( )
Adult lymphoma ( )
Autism ( )
Glomuvenous malformation ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Lymphoma ( )
Pediatric lymphoma ( )
Rett syndrome ( )
Schistosomiasis ( )
Toxoplasmosis ( )
UniProt ID
DCTN3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07426
Sequence
MAGLTDLQRLQARVEELERWVYGPGGARGSRKVADGLVKVQVALGNISSKRERVKILYKK
IEDLIKYLDPEYIDRIAIPDASKLQFILAEEQFILSQVALLEQVNALVPMLDSAHIKAVP
EHAARLQRLAQIHIQQQDQCVEITEESKALLEEYNKTTMLLSKQFVQWDELLCQLEAATQ
VKPAEE
Function Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. Together with dynein may be involved in spindle assembly and cytokinesis.
Tissue Specificity Ubiquitously expressed. Highly expressed in muscle and pancreas and detected at lower levels in brain.
KEGG Pathway
Motor proteins (hsa04814 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Salmonella infection (hsa05132 )
Reactome Pathway
Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942 )
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497 )
Loss of Nlp from mitotic centrosomes (R-HSA-380259 )
Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270 )
Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284 )
Recruitment of NuMA to mitotic centrosomes (R-HSA-380320 )
Anchoring of the basal body to the plasma membrane (R-HSA-5620912 )
COPI-mediated anterograde transport (R-HSA-6807878 )
COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436 )
AURKA Activation by TPX2 (R-HSA-8854518 )
MHC class II antigen presentation (R-HSA-2132295 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Tuberculosis DIS2YIMD Definitive Biomarker [1]
Arthritis DIST1YEL Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Chronic granulomatous disease DIS9ZR24 Strong Genetic Variation [4]
Estrogen-receptor positive breast cancer DIS1H502 Strong Biomarker [5]
facioscapulohumeral muscular dystrophy DISSE0H0 Strong Biomarker [6]
Frontometaphyseal dysplasia 1 DIS2MB3L Strong Biomarker [6]
Head-neck squamous cell carcinoma DISF7P24 Strong Genetic Variation [7]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [8]
Lyme disease DISO70G5 Strong Biomarker [2]
Medullary thyroid gland carcinoma DISHBL3K Strong Biomarker [9]
Neoplasm DISZKGEW Strong Genetic Variation [7]
Obstructive sleep apnea DIS0SVD1 Strong Genetic Variation [10]
Oral cancer DISLD42D Strong Altered Expression [11]
Oral cavity carcinoma DISZXMVL Strong Altered Expression [11]
Polycystic kidney disease DISWS3UY Strong Genetic Variation [12]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified DIS5OHQF Strong Biomarker [13]
Syphilis DISJ73BS Strong Biomarker [2]
Advanced cancer DISAT1Z9 moderate Biomarker [14]
Adult lymphoma DISK8IZR Limited Genetic Variation [15]
Autism DISV4V1Z Limited Genetic Variation [16]
Glomuvenous malformation DIS5UNDD Limited Genetic Variation [17]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [18]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [8]
Lymphoma DISN6V4S Limited Genetic Variation [15]
Pediatric lymphoma DIS51BK2 Limited Genetic Variation [15]
Rett syndrome DISGG5UV Limited Biomarker [16]
Schistosomiasis DIS6PD44 Limited Biomarker [19]
Toxoplasmosis DISYP8FH Limited Biomarker [20]
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⏷ Show the Full List of 29 Disease(s)
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 increases the methylation of Dynactin subunit 3 (DCTN3). [21]
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7 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 Dynactin subunit 3 (DCTN3). [22]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Dynactin subunit 3 (DCTN3). [23]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Dynactin subunit 3 (DCTN3). [24]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Dynactin subunit 3 (DCTN3). [25]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Dynactin subunit 3 (DCTN3). [26]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dynactin subunit 3 (DCTN3). [27]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Dynactin subunit 3 (DCTN3). [28]
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⏷ Show the Full List of 7 Drug(s)

References

1 Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis.Clin Proteomics. 2017 Nov 2;14:36. doi: 10.1186/s12014-017-9171-z. eCollection 2017.
2 A chromosomal Borrelia burgdorferi gene encodes a 22-kilodalton lipoprotein, P22, that is serologically recognized in Lyme disease.J Clin Microbiol. 1994 Apr;32(4):876-83. doi: 10.1128/jcm.32.4.876-883.1994.
3 Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status.Mol Cancer Res. 2007 Sep;5(9):881-90. doi: 10.1158/1541-7786.MCR-07-0055.
4 Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells.Int J Nanomedicine. 2017 Mar 20;12:2161-2177. doi: 10.2147/IJN.S128611. eCollection 2017.
5 Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer.J Nanobiotechnology. 2018 Feb 20;16(1):17. doi: 10.1186/s12951-018-0345-2.
6 Interaction of foot-and-mouth disease virus nonstructural protein 3A with host protein DCTN3 is important for viral virulence in cattle.J Virol. 2014 Mar;88(5):2737-47. doi: 10.1128/JVI.03059-13. Epub 2013 Dec 18.
7 Genomic assessments of the frequent loss of heterozygosity region on 8p21.3-p22 in head and neck squamous cell carcinoma.Cancer Genet Cytogenet. 2007 Jul 15;176(2):100-6. doi: 10.1016/j.cancergencyto.2007.04.003.
8 Hepatitis B Virus Precore Protein p22 Inhibits Alpha Interferon Signaling by Blocking STAT Nuclear Translocation.J Virol. 2019 Jun 14;93(13):e00196-19. doi: 10.1128/JVI.00196-19. Print 2019 Jul 1.
9 Site-directed chromosome rearrangements in skin fibroblasts from persons carrying genes for hereditary neoplasms.Cancer Res. 1980 Dec;40(12):4796-803.
10 Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?.Antioxid Redox Signal. 2012 Jan 15;16(2):171-7. doi: 10.1089/ars.2011.4189. Epub 2011 Oct 12.
11 Recurring DNA copy number gain at chromosome 9p13 plays a role in the activation of multiple candidate oncogenes in progressing oral premalignant lesions.Cancer Med. 2014 Oct;3(5):1170-84. doi: 10.1002/cam4.307. Epub 2014 Jul 24.
12 Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient Mice.J Am Soc Nephrol. 2018 Sep;29(9):2310-2325. doi: 10.1681/ASN.2018010074. Epub 2018 Jul 24.
13 ins(6;11) in a case of peripheral T-cell lymphoma.Cancer Genet Cytogenet. 1987 Aug;27(2):367-9. doi: 10.1016/0165-4608(87)90021-5.
14 Development of P22 viral capsid nanocomposites as anti-cancer drug, bortezomib (BTZ), delivery nanoplatforms.Macromol Biosci. 2014 Apr;14(4):557-64. doi: 10.1002/mabi.201300401.
15 Structural abnormalities of the X chromosome in non-Hodgkin's lymphoma.Leukemia. 1993 Jun;7(6):848-52.
16 A "new" chromosome marker common to the Rett syndrome and infantile autism? The frequency of fragile sites at X p22 in 81 children with infantile autism, childhood psychosis and the Rett syndrome.Brain Dev. 1985;7(3):365-7. doi: 10.1016/s0387-7604(85)80046-2.
17 Genetic analysis of a family with hereditary glomuvenous malformations.Australas J Dermatol. 2007 Aug;48(3):170-3. doi: 10.1111/j.1440-0960.2007.00373.x.
18 Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus.Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4641-5. doi: 10.1073/pnas.88.11.4641.
19 Immunization with rP22 induces protective immunity against Schistosoma mansoni: effects on granuloma down-modulation and cytokine production.Immunol Lett. 2011 Dec 30;141(1):123-33. doi: 10.1016/j.imlet.2011.09.003. Epub 2011 Sep 17.
20 P35 and P22 Toxoplasma gondii antigens abbreviate regions to diagnose acquired toxoplasmosis during pregnancy: toward single-sample assays.Clin Chem Lab Med. 2017 Mar 1;55(4):595-604. doi: 10.1515/cclm-2016-0331.
21 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.
22 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
23 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
24 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.
25 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
26 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
27 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.
28 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.