Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZVSU0X)

• DOT Name: SERPINE1 mRNA-binding protein 1 (SERBP1)
• Synonyms: PAI1 RNA-binding protein 1; PAI-RBP1; Plasminogen activator inhibitor 1 RNA-binding protein
• Gene Name: SERBP1
• Related Disease:
  Epithelial ovarian cancer
  Gastric cancer
  Gastric neoplasm
  Glioma
  Hereditary diffuse gastric adenocarcinoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pre-eclampsia
  Spondylocarpotarsal synostosis syndrome
  Hepatocellular carcinoma
  Pancreatic cancer
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Asthma
• UniProt ID: SERB1_HUMAN
• PDB ID: 4V6X; 6Z6M; 6Z6N
• Pfam ID: PF04774 ; PF16174
• Sequence:
  MPGHLQEGFGCVVTNRFDQLFDDESDPFEVLKAAENKKKEAGGGGVGGPGAKSAAQAAAQ
  TNSNAAGKQLRKESQKDRKNPLPPSVGVVDKKEETQPPVALKKEGIRRVGRRPDQQLQGE
  GKIIDRRPERRPPRERRFEKPLEEKGEGGEFSVDRPIIDRPIRGRGGLGRGRGGRGRGMG
  RGDGFDSRGKREFDRHSGSDRSSFSHYSGLKHEDKRGGSGSHNWGTVKDELTESPKYIQK
  QISYNYSDLDQSNVTEETPEGEEHHPVADTENKENEVEEVKEEGPKEMTLDEWKAIQNKD
  RAKVEFNIRKPNEGADGQWKKGFVLHKSKSEEAHAEDSVMDHHFRKPANDITSQLEINFG
  DLGRPGRGGRGGRGGRGRGGRPNRGSRTDKSSASAPDVDDPEAFPALA
• Function: Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation. Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state. May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay. Seems to play a role in PML-nuclear bodies formation.
• Tissue Specificity: Expressed at high level in the heart, skeletal muscle and kidney, and at low levels in placenta, liver and brain.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Pre-eclampsia	DISY7Q29	Strong	Genetic Variation	[5]
Spondylocarpotarsal synostosis syndrome	DISF9VP3	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[7]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[8]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Altered Expression	[9]
Prostate cancer	DISF190Y	Disputed	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Disputed	Biomarker	[10]
Asthma	DISW9QNS	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	SERPINE1 mRNA-binding protein 1 (SERBP1) affects the binding of 4-hydroxy-2-nonenal.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[19]
Selenium	DM25CGV	Approved	Selenium decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[20]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[21]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[22]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[20]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[23]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[28]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of SERPINE1 mRNA-binding protein 1 (SERBP1).	[30]

3 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 SERPINE1 mRNA-binding protein 1 (SERBP1).	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of SERPINE1 mRNA-binding protein 1 (SERBP1).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of SERPINE1 mRNA-binding protein 1 (SERBP1).	[29]

References

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• [2] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [3] Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.Biomed Res Int. 2016;2016:8065830. doi: 10.1155/2016/8065830. Epub 2016 Jun 1.
• [4] Differential expression of PAI-RBP1, C1orf142, and COTL1 in non-small cell lung cancer cell lines with different tumor metastatic potential.J Investig Med. 2012 Apr;60(4):689-94. doi: 10.2310/JIM.0b013e31824963b6.
• [5] Relationship between polymorphisms in thrombophilic genes and preeclampsia in a Brazilian population.Blood Cells Mol Dis. 2006 Sep-Oct;37(2):107-10. doi: 10.1016/j.bcmd.2006.07.005. Epub 2006 Sep 11.
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• [7] MiR-218 suppresses the metastasis and EMT of HCC cells via targeting SERBP1.Acta Biochim Biophys Sin (Shanghai). 2017 May 1;49(5):383-391. doi: 10.1093/abbs/gmx017.
• [8] LncRNA-PVT1 promotes pancreatic cancer cells proliferation and migration through acting as a molecular sponge to regulate miR-448.J Cell Physiol. 2018 May;233(5):4044-4055. doi: 10.1002/jcp.26072. Epub 2017 Nov 30.
• [9] The HMGA2-IMP2 Pathway Promotes Granulosa Cell Proliferation in Polycystic Ovary Syndrome.J Clin Endocrinol Metab. 2019 Apr 1;104(4):1049-1059. doi: 10.1210/jc.2018-00544.
• [10] Loss of miR-26a-5p promotes proliferation, migration, and invasion in prostate cancer through negatively regulating SERBP1.Tumour Biol. 2016 Sep;37(9):12843-12854. doi: 10.1007/s13277-016-5158-z. Epub 2016 Jul 23.
• [11] Polymorphism 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene is associated with IgE-mediated allergic diseases and asthma in the Czech population.Allergy. 2002 May;57(5):446-8. doi: 10.1034/j.1398-9995.2002.03582.x.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [14] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] 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.
• [19] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [20] 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.
• [21] 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.
• [22] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [23] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [24] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [25] 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.
• [26] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [27] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [28] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [29] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [30] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [31] 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.