Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT8IVS7)

• DOT Name: Prominin-2 (PROM2)
• Synonyms: PROM-2; Prominin-like protein 2; hPROML2
• Gene Name: PROM2
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Hepatocellular carcinoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Nervous system disease
• UniProt ID: PROM2_HUMAN
• Pfam ID: PF05478
• Sequence:
  MKHTLALLAPLLGLGLGLALSQLAAGATDCKFLGPAEHLTFTPAARARWLAPRVRAPGLL
  DSLYGTVRRFLSVVQLNPFPSELVKALLNELASVKVNEVVRYEAGYVVCAVIAGLYLLLV
  PTAGLCFCCCRCHRRCGGRVKTEHKALACERAALMVFLLLTTLLLLIGVVCAFVTNQRTH
  EQMGPSIEAMPETLLSLWGLVSDVPQELQAVAQQFSLPQEQVSEELDGVGVSIGSAIHTQ
  LRSSVYPLLAAVGSLGQVLQVSVHHLQTLNATVVELQAGQQDLEPAIREHRDRLLELLQE
  ARCQGDCAGALSWARTLELGADFSQVPSVDHVLHQLKGVPEANFSSMVQEENSTFNALPA
  LAAMQTSSVVQELKKAVAQQPEGVRTLAEGFPGLEAASRWAQALQEVEESSRPYLQEVQR
  YETYRWIVGCVLCSVVLFVVLCNLLGLNLGIWGLSARDDPSHPEAKGEAGARFLMAGVGL
  SFLFAAPLILLVFATFLVGGNVQTLVCQSWENGELFEFADTPGNLPPSMNLSQLLGLRKN
  ISIHQAYQQCKEGAALWTVLQLNDSYDLEEHLDINQYTNKLRQELQSLKVDTQSLDLLSS
  AARRDLEALQSSGLQRIHYPDFLVQIQRPVVKTSMEQLAQELQGLAQAQDNSVLGQRLQE
  EAQGLRNLHQEKVVPQQSLVAKLNLSVRALESSAPNLQLETSDVLANVTYLKGELPAWAA
  RILRNVSECFLAREMGYFSQYVAWVREEVTQRIATCQPLSGALDNSRVILCDMMADPWNA
  FWFCLAWCTFFLIPSIIFAVKTSKYFRPIRKRLSSTSSEETQLFHIPRVTSLKL
• Tissue Specificity: Present in saliva within small membrane particles (at protein level). Expressed in kidney, prostate, trachea, esophagus, salivary gland, thyroid gland, mammary gland adrenal gland, placenta, stomach, spinal cord and liver. In submucosal tumor, expressed in spindle-shaped or stellate stromal cells. Expressed in prostate cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Posttranslational Modification	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[6]

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 Prominin-2 (PROM2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Prominin-2 (PROM2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prominin-2 (PROM2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prominin-2 (PROM2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Prominin-2 (PROM2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Prominin-2 (PROM2).	[11]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Prominin-2 (PROM2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Prominin-2 (PROM2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prominin-2 (PROM2).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Prominin-2 (PROM2).	[16]

References

• [1] PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis.Cancer Gene Ther. 2020 Apr;27(3-4):147-167. doi: 10.1038/s41417-019-0109-7. Epub 2019 Jun 5.
• [2] CRTC1 gene is differentially methylated in the human hippocampus in Alzheimer's disease.Alzheimers Res Ther. 2016 Apr 19;8(1):15. doi: 10.1186/s13195-016-0183-0.
• [3] Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer.Cell Biol Toxicol. 2016 Oct;32(5):419-35. doi: 10.1007/s10565-016-9343-z. Epub 2016 Jun 15.
• [4] Identification and characterization of a novel testosterone-regulated prominin-like gene in the rat ventral prostate.Endocrinology. 2002 Dec;143(12):4788-96. doi: 10.1210/en.2002-220522.
• [5] Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.Clin Cancer Res. 2006 Dec 1;12(23):6937-45. doi: 10.1158/1078-0432.CCR-06-1268.
• [6] Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism.Neurobiol Dis. 2011 Feb;41(2):279-90. doi: 10.1016/j.nbd.2010.09.016. Epub 2010 Sep 29.
• [7] 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.
• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] 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.
• [16] 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.