Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDO6CMY)

• DOT Name: Ras-like protein family member 11A (RASL11A)
• Synonyms: EC 3.6.5.2
• Gene Name: RASL11A
• Related Disease:
  Colorectal carcinoma
  Prostate neoplasm
  Endometriosis
  Colorectal neoplasm
• UniProt ID: RSLBA_HUMAN
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MRPLSMSGHFLLAPIPESSSDYLLPKDIKLAVLGAGRVGKSAMIVRFLTKRFIGDYEPNT
  GKLYSRLVYVEGDQLSLQIQDTPGGVQIQDSLPQVVDSLSKCVQWAEGFLLVYSITDYDS
  YLSIRPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSE
  NYEDVCDVFQHLCKEVSKMHGLSGERRRASIIPRPRSPNMQDLKRRFKQALSPKVKAPSA
  LG
• Function: Regulator of rDNA transcription. Acts in cooperation UBF/UBTF and positively regulates RNA polymerase I transcription.
• Tissue Specificity: Widely expressed. Down-regulated in prostate tumors compared to normal prostate tissue. High levels found in colon tumor and normal colon tissue followed by small intestine, liver, jejunum, ileum, bladder and aorta. Lowest levels observed in endothelial cells.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Disputed	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-like protein family member 11A (RASL11A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-like protein family member 11A (RASL11A).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-like protein family member 11A (RASL11A).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ras-like protein family member 11A (RASL11A).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras-like protein family member 11A (RASL11A).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ras-like protein family member 11A (RASL11A).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Ras-like protein family member 11A (RASL11A).	[3]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ras-like protein family member 11A (RASL11A).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Ras-like protein family member 11A (RASL11A).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-like protein family member 11A (RASL11A).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-like protein family member 11A (RASL11A).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras-like protein family member 11A (RASL11A).	[15]

References

• [1] Promoter capture Hi-C-based identification of recurrent noncoding mutations in colorectal cancer.Nat Genet. 2018 Oct;50(10):1375-1380. doi: 10.1038/s41588-018-0211-z. Epub 2018 Sep 17.
• [2] RASL11A, member of a novel small monomeric GTPase gene family, is down-regulated in prostate tumors.Biochem Biophys Res Commun. 2004 Apr 9;316(3):618-27. doi: 10.1016/j.bbrc.2004.02.091.
• [3] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [4] Induced Chromosomal Aneuploidy Results in Global and Consistent Deregulation of the Transcriptome of Cancer Cells.Neoplasia. 2019 Jul;21(7):721-729. doi: 10.1016/j.neo.2019.04.009. Epub 2019 Jun 4.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] 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.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] 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.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.