Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR7WJES)

• DOT Name: Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2)
• Synonyms: Dynein light intermediate chain 2, cytosolic; LIC-2; LIC53/55
• Gene Name: DYNC1LI2
• Related Disease: Influenza
• UniProt ID: DC1L2_HUMAN
• PDB ID: 6F1T; 6F1Y; 6F38; 6F3A; 7Z8F; 7Z8I; 7Z8J; 7Z8K; 7Z8L
• Pfam ID: PF05783
• Sequence:
  MAPVGVEKKLLLGPNGPAVAAAGDLTSEEEEGQSLWSSILSEVSTRARSKLPSGKNILVF
  GEDGSGKTTLMTKLQGAEHGKKGRGLEYLYLSVHDEDRDDHTRCNVWILDGDLYHKGLLK
  FAVSAESLPETLVIFVADMSRPWTVMESLQKWASVLREHIDKMKIPPEKMRELERKFVKD
  FQDYMEPEEGCQGSPQRRGPLTSGSDEENVALPLGDNVLTHNLGIPVLVVCTKCDAVSVL
  EKEHDYRDEHLDFIQSHLRRFCLQYGAALIYTSVKEEKNLDLLYKYIVHKTYGFHFTTPA
  LVVEKDAVFIPAGWDNEKKIAILHENFTTVKPEDAYEDFIVKPPVRKLVHDKELAAEDEQ
  VFLMKQQSLLAKQPATPTRASESPARGPSGSPRTQGRGGPASVPSSSPGTSVKKPDPNIK
  NNAASEGVLASFFNSLLSKKTGSPGSPGAGGVQSTAKKSGQKTVLSNVQEELDRMTRKPD
  SMVTNSSTENEA
• Function: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
• KEGG Pathway:
  Phagosome (hsa04145)
  Motor proteins (hsa04814)
  Vasopressin-regulated water reabsorption (hsa04962)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  Mitotic Prometaphase (R-HSA-68877)
  HCMV Early Events (R-HSA-9609690)
  Aggrephagy (R-HSA-9646399)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Genetic Variation	[1]

11 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 Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[8]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[9]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[10]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[13]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[6]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Cytoplasmic dynein 1 light intermediate chain 2 (DYNC1LI2).	[14]

References

• [1] The role of lic2B in lipopolysaccharide biosynthesis in Haemophilus influenzae strain Eagan.Carbohydr Res. 2011 Jul 15;346(10):1262-6. doi: 10.1016/j.carres.2011.04.016. Epub 2011 Apr 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] 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.
• [9] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [14] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.