Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM7C943)

DOT Name Dynactin subunit 4 (DCTN4)
Synonyms Dyn4; Dynactin subunit p62
Gene Name DCTN4
Related Disease
Adenocarcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Amyloidosis ( )
Amyotrophic lateral sclerosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Cholangiocarcinoma ( )
Colorectal carcinoma ( )
Cystic fibrosis ( )
Epithelial ovarian cancer ( )
Fatty liver disease ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Inclusion body myositis ( )
Motor neurone disease ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Polymyositis ( )
Pseudomonas infection ( )
Rheumatoid arthritis ( )
Sclerosing cholangitis ( )
Skin cancer ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Immunodeficiency ( )
Paget's disease ( )
B-cell neoplasm ( )
Clear cell renal carcinoma ( )
Liver cancer ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary fibrosis ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
UniProt ID
DCTN4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF05502
Sequence
MASLLQSDRVLYLVQGEKKVRAPLSQLYFCRYCSELRSLECVSHEVDSHYCPSCLENMPS
AEAKLKKNRCANCFDCPGCMHTLSTRATSISTQLPDDPAKTTMKKAYYLACGFCRWTSRD
VGMADKSVASGGWQEPENPHTQRMNKLIEYYQQLAQKEKVERDRKKLARRRNYMPLAFSD
KYGLGTRLQRPRAGASISTLAGLSLKEGEDQKEIKIEPAQAVDEVEPLPEDYYTRPVNLT
EVTTLQQRLLQPDFQPVCASQLYPRHKHLLIKRSLRCRKCEHNLSKPEFNPTSIKFKIQL
VAVNYIPEVRIMSIPNLRYMKESQVLLTLTNPVENLTHVTLFECEEGDPDDINSTAKVVV
PPKELVLAGKDAAAEYDELAEPQDFQDDPDIIAFRKANKVGIFIKVTPQREEGEVTVCFK
MKHDFKNLAAPIRPIEESDQGTEVIWLTQHVELSLGPLLP
Function Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
KEGG Pathway
Motor proteins (hsa04814 )
Vasopressin-regulated water reabsorption (hsa04962 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Salmonella infection (hsa05132 )
Reactome Pathway
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497 )
COPI-mediated anterograde transport (R-HSA-6807878 )
COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436 )
MHC class II antigen presentation (R-HSA-2132295 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Biomarker [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Amyloidosis DISHTAI2 Strong Altered Expression [4]
Amyotrophic lateral sclerosis DISF7HVM Strong Genetic Variation [5]
Arteriosclerosis DISK5QGC Strong Biomarker [6]
Atherosclerosis DISMN9J3 Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Cholangiocarcinoma DIS71F6X Strong Genetic Variation [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [3]
Cystic fibrosis DIS2OK1Q Strong Biomarker [9]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [10]
Fatty liver disease DIS485QZ Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Altered Expression [12]
Glioblastoma multiforme DISK8246 Strong Biomarker [2]
Glioma DIS5RPEH Strong Biomarker [13]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [3]
Inclusion body myositis DISZXXG5 Strong Biomarker [15]
Motor neurone disease DISUHWUI Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [19]
Obesity DIS47Y1K Strong Biomarker [6]
Ovarian cancer DISZJHAP Strong Genetic Variation [10]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [10]
Parkinson disease DISQVHKL Strong Biomarker [20]
Polymyositis DIS5DHFP Strong Biomarker [21]
Pseudomonas infection DIS9WYLA Strong Biomarker [22]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [23]
Sclerosing cholangitis DIS7GZNB Strong Genetic Variation [8]
Skin cancer DISTM18U Strong Altered Expression [24]
Stomach cancer DISKIJSX Strong Altered Expression [12]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [25]
Immunodeficiency DIS093I0 moderate Biomarker [26]
Paget's disease DISO3MC0 Disputed Biomarker [27]
B-cell neoplasm DISVY326 Limited Biomarker [28]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [29]
Liver cancer DISDE4BI Limited Altered Expression [3]
Lung adenocarcinoma DISD51WR Limited Genetic Variation [30]
Lung cancer DISCM4YA Limited Altered Expression [3]
Lung carcinoma DISTR26C Limited Altered Expression [3]
Melanoma DIS1RRCY Limited Biomarker [31]
Prostate cancer DISF190Y Limited Biomarker [32]
Prostate carcinoma DISMJPLE Limited Biomarker [32]
Pulmonary fibrosis DISQKVLA Limited Biomarker [33]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [29]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [34]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Dynactin subunit 4 (DCTN4). [35]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Dynactin subunit 4 (DCTN4). [36]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Dynactin subunit 4 (DCTN4). [37]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Dynactin subunit 4 (DCTN4). [38]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Dynactin subunit 4 (DCTN4). [39]
Marinol DM70IK5 Approved Marinol decreases the expression of Dynactin subunit 4 (DCTN4). [40]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Dynactin subunit 4 (DCTN4). [44]
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⏷ Show the Full List of 7 Drug(s)
3 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 Dynactin subunit 4 (DCTN4). [41]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Dynactin subunit 4 (DCTN4). [42]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Dynactin subunit 4 (DCTN4). [43]
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References

1 Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma.Anticancer Res. 2019 Dec;39(12):6711-6722. doi: 10.21873/anticanres.13886.
2 HMGB1-Induced p62 Overexpression Promotes Snail-Mediated Epithelial-Mesenchymal Transition in Glioblastoma Cells via the Degradation of GSK-3.Theranostics. 2019 Mar 16;9(7):1909-1922. doi: 10.7150/thno.30578. eCollection 2019.
3 p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor.Cell Prolif. 2019 May;52(3):e12585. doi: 10.1111/cpr.12585. Epub 2019 Feb 22.
4 Orientin Improves Cognition by Enhancing Autophagosome Clearance in an Alzheimer's Mouse Model.J Mol Neurosci. 2019 Oct;69(2):246-253. doi: 10.1007/s12031-019-01353-5. Epub 2019 Jun 26.
5 An FTLD-associated SQSTM1 variant impacts Nrf2 and NF-B signalling and is associated with reduced phosphorylation of p62.Mol Cell Neurosci. 2019 Jul;98:32-45. doi: 10.1016/j.mcn.2019.04.001. Epub 2019 Apr 4.
6 p62/SQSTM1 and Selective Autophagy in Cardiometabolic Diseases.Antioxid Redox Signal. 2019 Aug 20;31(6):458-471. doi: 10.1089/ars.2018.7649. Epub 2019 Feb 11.
7 IL-1 induces p62/SQSTM1 and autophagy in ER(+) /PR(+) BCa cell lines concomitant with ER and PR repression, conferring an ER(-) /PR(-) BCa-like phenotype.J Cell Biochem. 2019 Feb;120(2):1477-1491. doi: 10.1002/jcb.27340. Epub 2018 Oct 15.
8 Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.Gut. 2018 Aug;67(8):1517-1524. doi: 10.1136/gutjnl-2016-313598. Epub 2017 Aug 4.
9 G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10.Sci Rep. 2019 Sep 9;9(1):12896. doi: 10.1038/s41598-019-46237-1.
10 Expression and role of autophagy-associated p62 (SQSTM1) in multidrug resistant ovarian cancer.Gynecol Oncol. 2018 Jul;150(1):143-150. doi: 10.1016/j.ygyno.2018.04.557. Epub 2018 Apr 24.
11 Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux.Sci Rep. 2018 Mar 7;8(1):4108. doi: 10.1038/s41598-018-22339-0.
12 SP1 reduces autophagic flux through activating p62 in gastric cancer cells.Mol Med Rep. 2018 Mar;17(3):4633-4638. doi: 10.3892/mmr.2018.8400. Epub 2018 Jan 9.
13 Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma.Oncogene. 2019 Dec;38(50):7473-7490. doi: 10.1038/s41388-019-0956-6. Epub 2019 Aug 23.
14 Hepatitis C virus core or NS3/4A protein expression preconditions hepatocytes against oxidative stress and endoplasmic reticulum stress.Redox Rep. 2019 Dec;24(1):17-26. doi: 10.1080/13510002.2019.1596431.
15 Association between TDP-43 and mitochondria in inclusion body myositis.Lab Invest. 2019 Jul;99(7):1041-1048. doi: 10.1038/s41374-019-0233-x. Epub 2019 Feb 11.
16 Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene.Neuropathol Appl Neurobiol. 2015 Aug;41(5):601-12. doi: 10.1111/nan.12178. Epub 2015 Apr 30.
17 Listeria-based hepatocellular carcinoma vaccine facilitates anti-PD-1 therapy by regulating macrophage polarization.Oncogene. 2020 Feb;39(7):1429-1444. doi: 10.1038/s41388-019-1072-3. Epub 2019 Oct 28.
18 The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes.J Clin Med. 2019 Aug 28;8(9):1322. doi: 10.3390/jcm8091322.
19 AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells. J Cell Biochem. 2019 Jan;120(1):756-767. doi: 10.1002/jcb.27434. Epub 2018 Aug 26.
20 The central regulator p62 between ubiquitin proteasome system and autophagy and its role in the mitophagy and Parkinson's disease.BMB Rep. 2020 Jan;53(1):56-63. doi: 10.5483/BMBRep.2020.53.1.283.
21 Sporadic inclusion body myositis: Diagnostic value of p62 immunostaining.Med Clin (Barc). 2019 Dec 13;153(11):437-440. doi: 10.1016/j.medcli.2019.04.022. Epub 2019 Jun 26.
22 Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.Nat Genet. 2012 Jul 8;44(8):886-9. doi: 10.1038/ng.2344.
23 Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR- Functional Module of Autophagy in Rheumatoid Arthritis.PPAR Res. 2019 May 7;2019:6403504. doi: 10.1155/2019/6403504. eCollection 2019.
24 Autophagy Controls CSL/RBPJ Stability through a p62/SQSTM1-Dependent Mechanism.Cell Rep. 2018 Sep 18;24(12):3108-3114.e4. doi: 10.1016/j.celrep.2018.08.043.
25 Nicotinate-curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus.CNS Neurosci Ther. 2019 Apr;25(4):430-441. doi: 10.1111/cns.13059. Epub 2018 Sep 9.
26 p62/SQSTM1 interacts with vimentin to enhance breast cancer metastasis.Carcinogenesis. 2017 Oct 26;38(11):1092-1103. doi: 10.1093/carcin/bgx099.
27 p62/sequestosome 1 deficiency accelerates osteoclastogenesis in vitro and leads to Paget's disease-like bone phenotypes in mice.J Biol Chem. 2018 Jun 15;293(24):9530-9541. doi: 10.1074/jbc.RA118.002449. Epub 2018 Mar 19.
28 Long Noncoding RNA KCNQ1OT1 Promotes the Progression of Non-Small Cell Lung Cancer via Regulating miR-204-5p/ATG3 Axis.Onco Targets Ther. 2019 Dec 10;12:10787-10797. doi: 10.2147/OTT.S226044. eCollection 2019.
29 Discovery of a novel 2,5-dihydroxycinnamic acid-based 5-lipoxygenase inhibitor that induces apoptosis and may impair autophagic flux in RCC4 renal cancer cells.Eur J Med Chem. 2019 Oct 1;179:347-357. doi: 10.1016/j.ejmech.2019.06.060. Epub 2019 Jun 23.
30 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
31 p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors.Cancer Cell. 2019 Jan 14;35(1):46-63.e10. doi: 10.1016/j.ccell.2018.11.008. Epub 2018 Dec 20.
32 Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.Cancer Cell. 2018 Apr 9;33(4):770-784.e6. doi: 10.1016/j.ccell.2018.03.001.
33 Beclin 1, LC3, and p62 expression in paraquat-induced pulmonary fibrosis.Hum Exp Toxicol. 2019 Jul;38(7):794-802. doi: 10.1177/0960327119842633. Epub 2019 Apr 12.
34 Investigation of cancer-associated fibroblasts and p62 expression in oral cancer before and after chemotherapy.J Craniomaxillofac Surg. 2018 Apr;46(4):605-610. doi: 10.1016/j.jcms.2017.12.016. Epub 2018 Jan 12.
35 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
36 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
37 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.
38 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
39 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.
40 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
41 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
42 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
43 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.
44 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.