Details of Drug Off-Target (DOT)

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

• DOT Name: Dynein light chain roadblock-type 1 (DYNLRB1)
• Synonyms: Bithoraxoid-like protein; BLP; Dynein light chain 2A, cytoplasmic; Dynein-associated protein Km23; Roadblock domain-containing protein 1
• Gene Name: DYNLRB1
• Related Disease:
  Gastric neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Small-cell lung cancer
• UniProt ID: DLRB1_HUMAN
• PDB ID: 1Z09; 2B95; 2E8J; 2HZ5; 6F1T; 6F1Z; 6F38; 6F3A; 6RLB; 6SC2; 7Z8F; 8J07
• Pfam ID: PF03259
• Sequence:
  MAEVEETLKRLQSQKGVQGIIVVNTEGIPIKSTMDNPTTTQYASLMHSFILKARSTVRDI
  DPQNDLTFLRIRSKKNEIMVAPDKDYFLIVIQNPTE
• 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.
• Tissue Specificity: High expression in heart, liver, brain and pancreas; moderate in placenta, skeletal muscle and kidney; low in lung, prostate, testis, small intestine and colon. Isoform 1 expression is up-regulated in 64% hepatocellular carcinoma (HCC) patients.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Salmonella infection (hsa05132)
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Definitive	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[5]

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 Dynein light chain roadblock-type 1 (DYNLRB1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[12]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Dynein light chain roadblock-type 1 (DYNLRB1).	[14]

1 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 increases the methylation of Dynein light chain roadblock-type 1 (DYNLRB1).	[13]

References

• [1] km23, a transforming growth factor-beta signaling component, is infrequently mutated in human colorectal and gastric cancers.Cancer Genet Cytogenet. 2007 Jun;175(2):173-4. doi: 10.1016/j.cancergencyto.2007.02.004.
• [2] km23-1/DYNLRB1 regulation of MEK/ERK signaling and R-Ras in invasive human colorectal cancer cells.Cell Biol Int. 2020 Jan;44(1):155-165. doi: 10.1002/cbin.11215. Epub 2019 Aug 28.
• [3] Genetic and epigenetic analysis of the putative tumor suppressor km23 in primary ovarian, breast, and colorectal cancers.Clin Cancer Res. 2006 Jun 15;12(12):3713-5. doi: 10.1158/1078-0432.CCR-06-0800.
• [4] Identification of two novel human dynein light chain genes, DNLC2A and DNLC2B, and their expression changes in hepatocellular carcinoma tissues from 68 Chinese patients.Gene. 2001 Dec 27;281(1-2):103-13. doi: 10.1016/s0378-1119(01)00787-9.
• [5] Clinical correlates of bombesin-like peptide receptor subtype expression in human lung cancer cells.Lung Cancer. 1996 Nov;15(3):341-54. doi: 10.1016/0169-5002(95)00597-8.
• [6] Evidence for autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer.Pulm Pharmacol Ther. 1999;12(5):291-302. doi: 10.1006/pupt.1999.0210.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] 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.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] 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.
• [14] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.