Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTESGJ1N)

DOT Name	Dynactin subunit 5 (DCTN5)
Synonyms	Dynactin subunit p25
Gene Name	DCTN5
Related Disease	Bipolar disorder ( ) Cystic fibrosis ( ) Psoriatic arthritis ( ) Respiratory disease ( ) Cutaneous melanoma ( ) Melanoma ( )
UniProt ID	DCTN5_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5NW4
Pfam ID	PF21711
Sequence	MELGELLYNKSEYIETASGNKVSRQSVLCGSQNIVLNGKTIVMNDCIIRGDLANVRVGRH CVVKSRSVIRPPFKKFSKGVAFFPLHIGDHVFIEEDCVVNAAQIGSYVHVGKNCVIGRRC VLKDCCKILDNTVLPPETVVPPFTVFSGCPGLFSGELPECTQELMIDVTKSYYQKFLPLT QV
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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[2]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[2]
Respiratory disease	DISGGAGJ	Strong	Genetic Variation	[2]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[3]
Melanoma	DIS1RRCY	Limited	Biomarker	[3]
------------------------------------------------------------------------------------


⏷ Show the Full List of 6 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

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 increases the expression of Dynactin subunit 5 (DCTN5).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dynactin subunit 5 (DCTN5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dynactin subunit 5 (DCTN5).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dynactin subunit 5 (DCTN5).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dynactin subunit 5 (DCTN5).	[8]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Dynactin subunit 5 (DCTN5).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dynactin subunit 5 (DCTN5).	[10]
------------------------------------------------------------------------------------


⏷ Show the Full List of 7 Drug(s)

References

1	Knockdown of mental disorder susceptibility genes disrupts neuronal network physiology in vitro.Mol Cell Neurosci. 2011 Jun;47(2):93-9. doi: 10.1016/j.mcn.2010.12.014. Epub 2011 Mar 30.
2	DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.Clin Respir J. 2016 Nov;10(6):777-783. doi: 10.1111/crj.12288. Epub 2015 Apr 15.
3	Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma.Med Sci Monit. 2018 Jun 4;24:3752-3763. doi: 10.12659/MSM.910566.
4	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
5	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.
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	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9	Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
10	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.