Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0BCPQG)

• DOT Name: Bone marrow proteoglycan (PRG2)
• Synonyms: BMPG; Proteoglycan 2
• Gene Name: PRG2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Mycoses
  Acute coronary syndrome
  Advanced cancer
  Alzheimer disease
  Benign prostatic hyperplasia
  Craniosynostosis
  Dilated cardiomyopathy 1A
  Duchenne muscular dystrophy
  Ehlers-Danlos syndrome, spondylodysplastic type, 1
  Endometrial cancer
  Endometrial carcinoma
  Lung cancer
  Lung carcinoma
  Muscular dystrophy
  Myositis disease
  Neoplasm
  Pachyonychia congenita 3
  Primary myelofibrosis
  Prostate neoplasm
  Vibrio cholerae infection
  Prostate cancer
  Prostate carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Asthma
  Eosinophilic esophagitis
• UniProt ID: PRG2_HUMAN
• PDB ID: 1H8U; 2BRS; 4QXX; 7Y5N; 8HGG
• Pfam ID: PF00059
• Sequence:
  MKLPLLLALLFGAVSALHLRSETSTFETPLGAKTLPEDEETPEQEMEETPCRELEEEEEW
  GSGSEDASKKDGAVESISVPDMVDKNLTCPEEEDTVKVVGIPGCQTCRYLLVRSLQTFSQ
  AWFTCRRCYRGNLVSIHNFNINYRIQCSVSALNQGQVWIGGRITGSGRCRRFQWVDGSRW
  NFAYWAAHQPWSRGGHCVALCTRGGHWRRAHCLRRLPFICSY
• Function: Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts as a proteinase inhibitor, reducing the activity of PAPPA.
• Tissue Specificity: Detected in plasma and urine (at protein level) . Detected in placenta (at protein level) . High levels of the proform in placenta and pregnancy serum; in placenta, localized to X cells of septa and anchoring villi. Lower levels in a variety of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow and colon.
• KEGG Pathway: Asthma (hsa05310)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Mycoses	DIS9K7PB	Definitive	Altered Expression	[2]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[6]
Craniosynostosis	DIS6J405	Strong	Altered Expression	[7]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[8]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[9]
Ehlers-Danlos syndrome, spondylodysplastic type, 1	DISJ607K	Strong	Genetic Variation	[10]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[11]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[9]
Myositis disease	DISCIXF0	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[14]
Pachyonychia congenita 3	DISZLC6C	Strong	Altered Expression	[15]
Primary myelofibrosis	DIS6L0CN	Strong	Altered Expression	[16]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[18]
Prostate cancer	DISF190Y	moderate	Biomarker	[6]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[6]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[19]
Asthma	DISW9QNS	Limited	Biomarker	[20]
Eosinophilic esophagitis	DISR8WSB	Limited	Biomarker	[21]

2 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 Bone marrow proteoglycan (PRG2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Bone marrow proteoglycan (PRG2).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bone marrow proteoglycan (PRG2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Bone marrow proteoglycan (PRG2).	[24]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Bone marrow proteoglycan (PRG2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Bone marrow proteoglycan (PRG2).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Bone marrow proteoglycan (PRG2).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Bone marrow proteoglycan (PRG2).	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Bone marrow proteoglycan (PRG2).	[30]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Bone marrow proteoglycan (PRG2).	[31]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Bone marrow proteoglycan (PRG2).	[32]

References

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• [5] Effective litmus gene test for monitoring the quality of blood samples: Application to Alzheimer's disease diagnostics.Sci Rep. 2017 Dec 4;7(1):16848. doi: 10.1038/s41598-017-17293-2.
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• [9] Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy.Hum Mol Genet. 2008 Aug 1;17(15):2280-92. doi: 10.1093/hmg/ddn129. Epub 2008 Apr 21.
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• [11] X chromosome-linked long noncoding RNA lnc-XLEC1 regulates c-Myc-dependent cell growth by collaborating with MBP-1 in endometrial cancer.Int J Cancer. 2019 Aug 15;145(4):927-940. doi: 10.1002/ijc.32166. Epub 2019 Feb 23.
• [12] Changes in gene expression in lungs of mice exposed to traffic-related air pollution.Mol Cell Probes. 2018 Jun;39:33-40. doi: 10.1016/j.mcp.2018.03.005. Epub 2018 Apr 3.
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• [15] Knockdown of MBP-1 in human prostate cancer cells delays cell cycle progression.J Biol Chem. 2006 Aug 18;281(33):23652-7. doi: 10.1074/jbc.M602930200. Epub 2006 Jun 8.
• [16] Clinical correlates of serum pro-major basic protein in a spectrum of eosinophilic disorders and myelofibrosis.Acta Haematol. 2008;120(3):158-64. doi: 10.1159/000178148. Epub 2008 Nov 28.
• [17] Carboxyl-terminal repressor domain of MBP-1 is sufficient for regression of prostate tumor growth in nude mice.Cancer Res. 2005 Feb 1;65(3):718-21.
• [18] Low concentrations mono-butyl phthalate stimulates steroidogenesis by facilitating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1).Chem Biol Interact. 2006 Dec 1;164(1-2):15-24. doi: 10.1016/j.cbi.2006.08.022. Epub 2006 Sep 1.
• [19] Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells.Cancer Res. 2006 Dec 15;66(24):11907-12. doi: 10.1158/0008-5472.CAN-06-2754.
• [20] Charcot-Leyden crystal protein/galectin-10 is a surrogate biomarker of eosinophilic airway inflammation in asthma.Biomark Med. 2019 Jun;13(9):715-724. doi: 10.2217/bmm-2018-0280. Epub 2019 Jun 3.
• [21] Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts.Dis Esophagus. 2019 Dec 30;32(11):doz055. doi: 10.1093/dote/doz055.
• [22] 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.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] 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.
• [25] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [26] 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.
• [27] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
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• [29] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [30] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [31] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [32] The effect of IFN-gamma and TNF-alpha on the eosinophilic differentiation and NADPH oxidase activation of human HL-60 clone 15 cells. J Interferon Cytokine Res. 2003 Dec;23(12):737-44.