Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT26QKCI)

• DOT Name: Dynein light chain Tctex-type 3 (DYNLT3)
• Synonyms: Protein 91/23; T-complex-associated testis-expressed 1-like
• Gene Name: DYNLT3
• Related Disease:
  Congenital stationary night blindness 2A
  Duchenne muscular dystrophy
  Epithelial ovarian cancer
  Myopia
  Night blindness
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Retinitis pigmentosa
• UniProt ID: DYLT3_HUMAN
• Pfam ID: PF03645
• Sequence:
  MEEYHRHCDEVGFNAEEAHNIVKECVDGVLGGEDYNHNNINQWTASIVEQSLTHLVKLGK
  AYKYIVTCAVVQKSAYGFHTASSCFWDTTSDGTCTVRWENRTMNCIVNVFAIAIVL
• 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. Probably binds BUB3 as part of transport cargo. Required for the efficient progression through mitosis.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Salmonella infection (hsa05132)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital stationary night blindness 2A	DISA57KI	Strong	Genetic Variation	[1]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Myopia	DISK5S60	Strong	Genetic Variation	[4]
Night blindness	DIS335K9	Strong	Genetic Variation	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[5]
Retinitis pigmentosa	DISCGPY8	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Dynein light chain Tctex-type 3 (DYNLT3) affects the binding of 4-hydroxy-2-nonenal.	[16]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Dynein light chain Tctex-type 3 (DYNLT3).	[15]

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 decreases the methylation of Dynein light chain Tctex-type 3 (DYNLT3).	[12]

References

• [1] Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp.Invest Ophthalmol Vis Sci. 1997 Dec;38(13):2750-5.
• [2] Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases.Gene. 2007 May 1;392(1-2):142-50. doi: 10.1016/j.gene.2006.11.023. Epub 2007 Jan 11.
• [3] Effects of dynein light chain Tctex-type 3 on the biological behavior of ovarian cancer.Cancer Manag Res. 2019 Jul 1;11:5925-5938. doi: 10.2147/CMAR.S205158. eCollection 2019.
• [4] Phenotype-genotype correlations in X linked retinitis pigmentosa.J Med Genet. 1992 Sep;29(9):615-23. doi: 10.1136/jmg.29.9.615.
• [5] Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease.Brain. 2012 Jul;135(Pt 7):2058-73. doi: 10.1093/brain/aws133. Epub 2012 Jun 19.
• [6] A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).Nat Genet. 1996 May;13(1):35-42. doi: 10.1038/ng0596-35.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [9] 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.
• [10] 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.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [16] Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.