Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8PIN9)

DOT Name Dynactin subunit 6 (DCTN6)
Synonyms Dynactin subunit p27; Protein WS-3
Gene Name DCTN6
Related Disease
Multiple endocrine neoplasia type 1 ( )
Adenoma ( )
B-cell neoplasm ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cholangiocarcinoma ( )
Classic Hodgkin lymphoma ( )
Colon cancer ( )
Endometrial carcinoma ( )
Epithelial ovarian cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Mantle cell lymphoma ( )
Melanoma ( )
Mesothelioma ( )
Metastatic malignant neoplasm ( )
Neuroblastoma ( )
Non-hodgkin lymphoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Plasma cell myeloma ( )
Renal cell carcinoma ( )
Small lymphocytic lymphoma ( )
Thyroid tumor ( )
Triple negative breast cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Uterine fibroids ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Gastrointestinal stromal tumour ( )
Liver cirrhosis ( )
Esophageal squamous cell carcinoma ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Colon carcinoma ( )
leukaemia ( )
Leukemia ( )
Liver cancer ( )
Nasopharyngeal carcinoma ( )
UniProt ID
DCTN6_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3TV0
Sequence
MAEKTQKSVKIAPGAVVCVESEIRGDVTIGPRTVIHPKARIIAEAGPIVIGEGNLIEEQA
LIINAYPDNITPDTEDPEPKPMIIGTNNVFEVGCYSQAMKMGDNNVIESKAYVGRNVILT
SGCIIGACCNLNTFEVIPENTVIYGADCLRRVQTERPQPQTLQLDFLMKILPNYHHLKKT
MKGSSTPVKN
Function Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
Tissue Specificity Ubiquitous.
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

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Multiple endocrine neoplasia type 1 DIS0RJRK Definitive Genetic Variation [1]
Adenoma DIS78ZEV Strong Biomarker [2]
B-cell neoplasm DISVY326 Strong Altered Expression [3]
Bladder cancer DISUHNM0 Strong Altered Expression [4]
Bone osteosarcoma DIST1004 Strong Posttranslational Modification [5]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Classic Hodgkin lymphoma DISV1LU6 Strong Altered Expression [8]
Colon cancer DISVC52G Strong Biomarker [9]
Endometrial carcinoma DISXR5CY Strong Biomarker [10]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [11]
Glioblastoma multiforme DISK8246 Strong Biomarker [12]
Glioma DIS5RPEH Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [14]
Lung cancer DISCM4YA Strong Altered Expression [15]
Lung carcinoma DISTR26C Strong Altered Expression [15]
Mantle cell lymphoma DISFREOV Strong Biomarker [16]
Melanoma DIS1RRCY Strong Biomarker [17]
Mesothelioma DISKWK9M Strong Biomarker [18]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [19]
Neuroblastoma DISVZBI4 Strong Altered Expression [20]
Non-hodgkin lymphoma DISS2Y8A Strong Altered Expression [21]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [22]
Osteosarcoma DISLQ7E2 Strong Posttranslational Modification [5]
Ovarian cancer DISZJHAP Strong Biomarker [11]
Ovarian neoplasm DISEAFTY Strong Biomarker [11]
Plasma cell myeloma DIS0DFZ0 Strong Posttranslational Modification [23]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [24]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [25]
Thyroid tumor DISLVKMD Strong Biomarker [26]
Triple negative breast cancer DISAMG6N Strong Altered Expression [27]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [4]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [4]
Uterine fibroids DISBZRMJ Strong Biomarker [28]
Acute myelogenous leukaemia DISCSPTN moderate Altered Expression [29]
Adult glioblastoma DISVP4LU moderate Biomarker [12]
Gastrointestinal stromal tumour DIS6TJYS moderate Altered Expression [30]
Liver cirrhosis DIS4G1GX moderate Biomarker [31]
Esophageal squamous cell carcinoma DIS5N2GV Disputed Altered Expression [32]
Thyroid cancer DIS3VLDH Disputed Biomarker [26]
Thyroid gland carcinoma DISMNGZ0 Disputed Biomarker [26]
Carcinoma DISH9F1N Limited Biomarker [33]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [24]
Colon carcinoma DISJYKUO Limited Biomarker [9]
leukaemia DISS7D1V Limited Biomarker [34]
Leukemia DISNAKFL Limited Biomarker [34]
Liver cancer DISDE4BI Limited Altered Expression [6]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [35]
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⏷ Show the Full List of 48 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 6 (DCTN6). [36]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Dynactin subunit 6 (DCTN6). [37]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Dynactin subunit 6 (DCTN6). [38]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Dynactin subunit 6 (DCTN6). [40]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Dynactin subunit 6 (DCTN6). [41]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Dynactin subunit 6 (DCTN6). [42]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Dynactin subunit 6 (DCTN6). [44]
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⏷ Show the Full List of 7 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Dynactin subunit 6 (DCTN6). [39]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Dynactin subunit 6 (DCTN6). [43]
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References

1 Hyperparathyroid genes: sequences reveal answers and questions.Endocr Pract. 2011 Jul-Aug;17 Suppl 3(Suppl 3):18-27. doi: 10.4158/EP11067.RA.
2 Expression of Cyclin E/Cdk2/p27(Kip1) in Growth Hormone Adenomas.World Neurosurg. 2019 Jan;121:e45-e53. doi: 10.1016/j.wneu.2018.08.209. Epub 2018 Sep 6.
3 Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors.Oncol Lett. 2019 Feb;17(2):2047-2056. doi: 10.3892/ol.2018.9845. Epub 2018 Dec 18.
4 Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin (ISO) on human bladder cancer cells.Carcinogenesis. 2018 Mar 8;39(3):482-492. doi: 10.1093/carcin/bgy015.
5 p27/Kip1 functions as a tumor suppressor and oncoprotein in osteosarcoma.Sci Rep. 2019 Apr 16;9(1):6161. doi: 10.1038/s41598-019-42450-0.
6 High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma.Oncotarget. 2017 Dec 19;9(10):8957-8971. doi: 10.18632/oncotarget.23420. eCollection 2018 Feb 6.
7 Phosphorylation of P27 by AKT is required for inhibition of cell cycle progression in cholangiocarcinoma.Dig Liver Dis. 2018 May;50(5):501-506. doi: 10.1016/j.dld.2017.12.021. Epub 2018 Jan 4.
8 Expression of Foxo3a in non-Hodgkin's lymphomas is correlated with cell cycle inhibitor p27.Eur J Haematol. 2008 Aug;81(2):83-93. doi: 10.1111/j.1600-0609.2008.01077.x. Epub 2008 Mar 19.
9 Construction and characterization of regulated cycle inhibiting factors induced upon Tet-On system in human colon cancer cell lines.Anticancer Drugs. 2018 Oct;29(9):854-860. doi: 10.1097/CAD.0000000000000654.
10 Loss of p27 Associated with Risk for Endometrial Carcinoma Arising in the Setting of Obesity.Curr Mol Med. 2016;16(3):252-65. doi: 10.2174/1566524016666160225153307.
11 Cell Cycle Regulator p27 Mediates Body Mass Index Effects in Ovarian Cancer in FIGO-stages I-II.Cancer Genomics Proteomics. 2019 Nov-Dec;16(6):443-450. doi: 10.21873/cgp.20148.
12 PKM2 uses control of HuR localization to regulate p27 and cell cycle progression in human glioblastoma cells.Int J Cancer. 2016 Jul 1;139(1):99-111. doi: 10.1002/ijc.30041. Epub 2016 Mar 2.
13 TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway.J Neurooncol. 2019 Nov;145(2):211-222. doi: 10.1007/s11060-019-03301-0. Epub 2019 Oct 11.
14 Gold nanoparticles-loaded anti-miR221 enhances antitumor effect of sorafenib in hepatocellular carcinoma cells.Int J Med Sci. 2019 Oct 21;16(12):1541-1548. doi: 10.7150/ijms.37427. eCollection 2019.
15 Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer.Int J Mol Sci. 2016 Mar 24;17(4):437. doi: 10.3390/ijms17040437.
16 Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma.J Cell Commun Signal. 2019 Sep;13(3):421-434. doi: 10.1007/s12079-018-0494-y. Epub 2018 Nov 21.
17 Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma.Med Sci Monit. 2018 Jun 4;24:3752-3763. doi: 10.12659/MSM.910566.
18 miR-182 and miR-183 Promote Cell Proliferation and Invasion by Targeting FOXO1 in Mesothelioma.Front Oncol. 2018 Oct 22;8:446. doi: 10.3389/fonc.2018.00446. eCollection 2018.
19 Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor metastasis via STAT3-mediated Twist1 upregulation.Oncogene. 2015 Oct;34(43):5447-59. doi: 10.1038/onc.2014.473. Epub 2015 Feb 16.
20 TIPE? suppresses growth and aggressiveness of hepatocellular carcinoma cells through downregulation of the phosphoinositide 3kinase/AKT signaling pathway.Mol Med Rep. 2018 May;17(5):7017-7026. doi: 10.3892/mmr.2018.8789. Epub 2018 Mar 20.
21 Reciprocal Cdc25A and p27 expression in B-cell non-Hodgkin lymphomas.Diagn Mol Pathol. 2003 Sep;12(3):128-32. doi: 10.1097/00019606-200309000-00003.
22 Cytoplasmic p27(Kip1) promotes tumorigenesis via suppression of RhoB activity.J Pathol. 2019 Jan;247(1):60-71. doi: 10.1002/path.5167. Epub 2018 Dec 11.
23 ADP-ribosylation factor 1 (ARF1) takes part in cell proliferation and cell adhesion-mediated drug resistance (CAM-DR).Ann Hematol. 2017 May;96(5):847-858. doi: 10.1007/s00277-017-2949-2. Epub 2017 Feb 25.
24 The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc.J Cancer. 2019 Aug 19;10(19):4662-4670. doi: 10.7150/jca.29280. eCollection 2019.
25 High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.Oncotarget. 2014 Jul 15;5(13):4694-708. doi: 10.18632/oncotarget.2100.
26 Rewiring of the apoptotic TGF--SMAD/NFB pathway through an oncogenic function of p27 in human papillary thyroid cancer.Oncogene. 2017 Feb 2;36(5):652-666. doi: 10.1038/onc.2016.233. Epub 2016 Jul 25.
27 Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells.Sci Rep. 2019 Sep 24;9(1):13748. doi: 10.1038/s41598-019-50141-z.
28 Activation of -Catenin Signaling and its Crosstalk With Estrogen and Histone Deacetylases in Human Uterine Fibroids.J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1517-35. doi: 10.1210/clinem/dgz227.
29 c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.J Cell Biochem. 2008 Aug 15;104(6):2091-106. doi: 10.1002/jcb.21765.
30 Cyclin D1 is a mediator of gastrointestinal stromal tumor KIT-independence.Oncogene. 2019 Sep;38(39):6615-6629. doi: 10.1038/s41388-019-0894-3. Epub 2019 Aug 1.
31 miR-181b promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients.Biochem Biophys Res Commun. 2012 Apr 27;421(1):4-8. doi: 10.1016/j.bbrc.2012.03.025. Epub 2012 Mar 13.
32 Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo.Int J Cancer. 2019 Aug 15;145(4):1007-1019. doi: 10.1002/ijc.32285. Epub 2019 Apr 3.
33 Predictive value of FHIT, p27, and pERK1/ERK2 in salivary gland carcinomas: a retrospective study.Clin Oral Investig. 2019 Oct;23(10):3801-3809. doi: 10.1007/s00784-019-02809-z. Epub 2019 Jan 23.
34 CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27(kip1) signaling.Haematologica. 2017 Apr;102(4):707-718. doi: 10.3324/haematol.2016.151555. Epub 2017 Jan 25.
35 Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27.Oncol Res. 2017 Nov 2;25(9):1431-1440. doi: 10.3727/096504017X14835311718295. Epub 2017 Jan 20.
36 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
37 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
38 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.
39 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
40 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
41 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
42 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
43 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
44 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.