Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLIT58K)

• DOT Name: Dynein light chain 2, cytoplasmic (DYNLL2)
• Synonyms: 8 kDa dynein light chain b; DLC8b; Dynein light chain LC8-type 2
• Gene Name: DYNLL2
• Related Disease:
  Breast cancer
  Endometrial cancer
  Endometrial carcinoma
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Advanced cancer
  Breast carcinoma
  Generalized anxiety disorder
  Panic disorder
  Rectal carcinoma
  Rectal neoplasm
  Social phobia
• UniProt ID: DYL2_HUMAN
• PDB ID: 2XQQ; 3P8M; 4D07; 7CNU
• Pfam ID: PF01221
• Sequence:
  MSDRKAVIKNADMSEDMQQDAVDCATQAMEKYNIEKDIAAYIKKEFDKKYNPTWHCIVGR
  NFGSYVTHETKHFIYFYLGQVAILLFKSG
• 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 changing or maintaining the spatial distribution of cytoskeletal structures.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Vasopressin-regulated water reabsorption (hsa04962)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)
  Macroautophagy (R-HSA-1632852)
  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)
  Intraflagellar transport (R-HSA-5620924)
  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)
  Activation of BMF and translocation to mitochondria (R-HSA-139910)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[2]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[1]
Generalized anxiety disorder	DISPSQCW	Limited	Biomarker	[6]
Panic disorder	DISD3VNY	Limited	Biomarker	[6]
Rectal carcinoma	DIS8FRR7	Limited	Altered Expression	[7]
Rectal neoplasm	DISB4UZ0	Limited	Altered Expression	[7]
Social phobia	DISQGN78	Limited	Biomarker	[6]

16 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 Dynein light chain 2, cytoplasmic (DYNLL2).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[20]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[21]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[22]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Dynein light chain 2, cytoplasmic (DYNLL2).	[21]

References

• [1] DLC2 operates as a tumor suppressor gene in breast cancer via the RhoGTPase pathway.Oncol Lett. 2019 Feb;17(2):2107-2116. doi: 10.3892/ol.2018.9874. Epub 2018 Dec 28.
• [2] Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer.BMC Med Genomics. 2011 Jan 12;4:6. doi: 10.1186/1755-8794-4-6.
• [3] DLC2 inhibits development of glioma through regulating the expression ratio of TAp73/TAp73.Am J Cancer Res. 2018 Jul 1;8(7):1200-1213. eCollection 2018.
• [4] Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma.Eur J Histochem. 2019 Feb 18;63(1):2981. doi: 10.4081/ejh.2019.2981.
• [5] High expression of DLC family proteins predicts better prognosis and inhibits tumor progression in NSCLC.Mol Med Rep. 2019 Jun;19(6):4881-4889. doi: 10.3892/mmr.2019.10146. Epub 2019 Apr 10.
• [6] An association analysis of murine anxiety genes in humans implicates novel candidate genes for anxiety disorders.Biol Psychiatry. 2008 Oct 15;64(8):672-680. doi: 10.1016/j.biopsych.2008.06.002. Epub 2008 Jul 17.
• [7] Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors.Int J Oncol. 2006 Nov;29(5):1127-32.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [17] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.
• [22] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.