Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1QN4LV)

• DOT Name: PRA1 family protein 2 (PRAF2)
• Gene Name: PRAF2
• Related Disease:
  Neuroblastoma
  Advanced cancer
  Esophageal squamous cell carcinoma
  Malignant glioma
  Neoplasm
  Cutaneous squamous cell carcinoma
  Hepatocellular carcinoma
• UniProt ID: PRAF2_HUMAN
• Pfam ID: PF03208
• Sequence:
  MSEVRLPPLRALDDFVLGSARLAAPDPCDPQRWCHRVINNLLYYQTNYLLCFGIGLALAG
  YVRPLHTLLSALVVAVALGVLVWAAETRAAVRRCRRSHPAACLAAVLAVGLLVLWVAGGA
  CTFLFSIAGPVLLILVHASLRLRNLKNKIENKIESIGLKRTPMGLLLEALGQEQEAGS
• Function: May be involved in ER/Golgi transport and vesicular traffic. Plays a proapoptotic role in cerulenin-induced neuroblastoma apoptosis.
• Tissue Specificity: Strong expression in the brain, small intestine, lung, spleen, and pancreas as well as in tumor tissues of the breast, colon, lung and ovary, with a weaker expression in normal tissues of the same patient. High expression in neuroblastic tumors. Strongly expressed in Purkinje cells and more moderately in cells of the molecular and the granular layers in the cerebellum. Detected in neuronal cells, but not in non-neuronal cells in the cerebral cortex, hippocampus, and lateral ventricles.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]

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 PRA1 family protein 2 (PRAF2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PRA1 family protein 2 (PRAF2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of PRA1 family protein 2 (PRAF2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of PRA1 family protein 2 (PRAF2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PRA1 family protein 2 (PRAF2).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of PRA1 family protein 2 (PRAF2).	[9]
Selenium	DM25CGV	Approved	Selenium increases the expression of PRA1 family protein 2 (PRAF2).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of PRA1 family protein 2 (PRAF2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of PRA1 family protein 2 (PRAF2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PRA1 family protein 2 (PRAF2).	[14]

References

• [1] PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma.Int J Oncol. 2013 Apr;42(4):1408-16. doi: 10.3892/ijo.2013.1836. Epub 2013 Feb 21.
• [2] Subcellular distribution and expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in malignant glioma: Influence on cell survival and migration.Cancer Sci. 2010 Jul;101(7):1624-31. doi: 10.1111/j.1349-7006.2010.01570.x. Epub 2010 Mar 19.
• [3] PRAF2 overexpression predicts poor prognosis and promotes tumorigenesis in esophageal squamous cell carcinoma.BMC Cancer. 2019 Jun 14;19(1):585. doi: 10.1186/s12885-019-5818-7.
• [4] PRAF2 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.Cancer Manag Res. 2018 Jul 25;10:2241-2248. doi: 10.2147/CMAR.S166789. eCollection 2018.
• [5] Long non-coding RNA HOTAIR functions as a competitive endogenous RNA to regulate PRAF2 expression by sponging miR-326 in cutaneous squamous cell carcinoma.Cancer Cell Int. 2019 Oct 21;19:270. doi: 10.1186/s12935-019-0992-x. eCollection 2019.
• [6] 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.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] 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.
• [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] 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.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.