Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHLC8TA)

• DOT Name: Dead end protein homolog 1 (DND1)
• Synonyms: RNA-binding motif, single-stranded-interacting protein 4
• Gene Name: DND1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Germ cell tumor
  Hepatocellular carcinoma
  Neoplasm
  Testicular germ cell tumor
  Adult teratoma
  Colorectal carcinoma
  Teratoma
  Adult germ cell tumor
  Germ cell tumour
• UniProt ID: DND1_HUMAN
• PDB ID: 6LE1; 7Q4L
• Pfam ID: PF14709 ; PF00076
• Sequence:
  MQSKRDCELWCERVNPENKAALEAWVRETGIRLVQVNGQRKYGGPPPGWVGSPPPAGSEV
  FIGRLPQDVYEHQLIPLFQRVGRLYEFRLMMTFSGLNRGFAYARYSSRRGAQAAIATLHN
  HPLRPSCPLLVCRSTEKCELSVDGLPPNLTRSALLLALQPLGPGLQEARLLPSPGPAPGQ
  IALLKFSSHRAAAMAKKALVEGQSHLCGEQVAVEWLKPDLKQRLRQQLVGPFLRSPQPEG
  SQLALARDKLGFQGARATLQLLCQRMKLGSPVFLTKCLGIGPAGWHRFWYQVVIPGHPVP
  FSGLIWVVLTLDGRDGHEVAKDAVSVRLLQALSESGANLLWSAGAEAGTMVKQ
• Function: RNA-binding factor that positively regulates gene expression by prohibiting miRNA-mediated gene suppression. Relieves miRNA repression in germline cells. Prohibits the function of several miRNAs by blocking the accessibility of target mRNAs. Sequence-specific RNA-binding factor that binds specifically to U-rich regions (URRs) in the 3' untranslated region (3'-UTR) of several mRNAs. Does not bind to miRNAs. May play a role during primordial germ cell (PGC) survival. However, does not seem to be essential for PGC migration.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Germ cell tumor	DIS62070	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[5]
Adult teratoma	DISBY81U	moderate	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[4]
Teratoma	DIS6ICY4	moderate	Biomarker	[6]
Adult germ cell tumor	DISJUCQ7	Limited	Biomarker	[7]
Germ cell tumour	DISOF3TK	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Dead end protein homolog 1 (DND1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dead end protein homolog 1 (DND1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dead end protein homolog 1 (DND1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dead end protein homolog 1 (DND1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dead end protein homolog 1 (DND1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dead end protein homolog 1 (DND1).	[12]

References

• [1] RNA-binding protein Dnd1 inhibits epithelial-mesenchymal transition and cancer stem cell-related traits on hepatocellular carcinoma cells.Biotechnol Lett. 2017 Sep;39(9):1359-1367. doi: 10.1007/s10529-017-2375-5. Epub 2017 Jun 7.
• [2] RNA-Binding Protein Dnd1 Promotes Breast Cancer Apoptosis by Stabilizing the Bim mRNA in a miR-221 Binding Site.Biomed Res Int. 2017;2017:9596152. doi: 10.1155/2017/9596152. Epub 2017 Jan 16.
• [3] Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.Genes Chromosomes Cancer. 2008 Mar;47(3):247-52. doi: 10.1002/gcc.20526.
• [4] MicroRNA-24 regulates the growth and chemosensitivity of the human colorectal cancer cells by targeting RNA-binding protein DND1.J BUON. 2019 Jul-Aug;24(4):1476-1481.
• [5] Screening for germline DND1 mutations in testicular cancer patients.Fam Cancer. 2010 Sep;9(3):439-42. doi: 10.1007/s10689-010-9340-y.
• [6] Derivation of pluripotent stem cells from nascent undifferentiated teratoma.Dev Biol. 2019 Feb 1;446(1):43-55. doi: 10.1016/j.ydbio.2018.11.020. Epub 2018 Dec 5.
• [7] The role of dead-end in germ-cell tumor development.Ann N Y Acad Sci. 2007 Dec;1120:181-6. doi: 10.1196/annals.1411.006. Epub 2007 Sep 28.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.