Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT48QD82)

DOT Name Proline-rich acidic protein 1 (PRAP1)
Synonyms Epididymis tissue protein Li 178; Uterine-specific proline-rich acidic protein
Gene Name PRAP1
Related Disease
Meningioma ( )
Acute myocardial infarction ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant soft tissue neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Quebec platelet disorder ( )
Retinoblastoma ( )
Sarcoma ( )
Seminoma ( )
Tarsal-carpal coalition syndrome ( )
Bone osteosarcoma ( )
Osteosarcoma ( )
Acute myelogenous leukaemia ( )
Glioma ( )
Rheumatoid arthritis ( )
Synovitis ( )
Thyroid gland papillary carcinoma ( )
Vernal keratoconjunctivitis ( )
UniProt ID
PRAP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15314
Sequence
MRRLLLVTSLVVVLLWEAGAVPAPKVPIKMQVKHWPSEQDPEKAWGARVVEPPEKDDQLV
VLFPVQKPKLLTTEEKPRGQGRGPILPGTKAWMETEDTLGHVLSPEPDHDSLYHPPPEED
QGEERPRLWVMPNHQVLLGPEEDQDHIYHPQ
Function
Lipid-binding protein which promotes lipid absorption by facilitating MTTP-mediated lipid transfer (mainly triglycerides and phospholipids) and MTTP-mediated apoB lipoprotein assembly and secretion. Protects the gastrointestinal epithelium from irradiation-induced apoptosis. May play an important role in maintaining normal growth homeostasis in epithelial cells. Involved in p53/TP53-dependent cell survival after DNA damage. May down-regulate the expression of MAD1L1 and exert a suppressive role in mitotic spindle assembly checkpoint in hepatocellular carcinomas.
Tissue Specificity
Highly expressed in the intestinal epithelial cells (at protein level) . Abundantly expressed in the epithelial cells of the liver, kidney and cervix. Significantly down-regulated in hepatocellular carcinoma and right colon adenocarcinoma compared with the respective adjacent normal tissues. Expressed in epididymis (at protein level).
KEGG Pathway
Autophagy - animal (hsa04140 )

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Meningioma DISPT4TG Definitive Posttranslational Modification [1]
Acute myocardial infarction DISE3HTG Strong Biomarker [2]
Adenocarcinoma DIS3IHTY Strong Altered Expression [3]
Adult glioblastoma DISVP4LU Strong Altered Expression [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Colon cancer DISVC52G Strong Altered Expression [3]
Colon carcinoma DISJYKUO Strong Altered Expression [3]
Endometrial cancer DISW0LMR Strong Genetic Variation [8]
Endometrial carcinoma DISXR5CY Strong Genetic Variation [8]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [9]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [10]
Lung cancer DISCM4YA Strong Biomarker [11]
Lung carcinoma DISTR26C Strong Biomarker [11]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [12]
Neoplasm DISZKGEW Strong Biomarker [13]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [14]
Pancreatic cancer DISJC981 Strong Biomarker [15]
Prostate cancer DISF190Y Strong Genetic Variation [16]
Prostate carcinoma DISMJPLE Strong Genetic Variation [16]
Quebec platelet disorder DIS2BK72 Strong Altered Expression [17]
Retinoblastoma DISVPNPB Strong Genetic Variation [18]
Sarcoma DISZDG3U Strong Biomarker [12]
Seminoma DIS3J8LJ Strong Altered Expression [19]
Tarsal-carpal coalition syndrome DISY90L2 Strong Altered Expression [20]
Bone osteosarcoma DIST1004 moderate Biomarker [21]
Osteosarcoma DISLQ7E2 moderate Biomarker [21]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [22]
Glioma DIS5RPEH Limited Altered Expression [4]
Rheumatoid arthritis DISTSB4J Limited Biomarker [23]
Synovitis DISW2GPY Limited Biomarker [23]
Thyroid gland papillary carcinoma DIS48YMM Limited Altered Expression [24]
Vernal keratoconjunctivitis DIS36LV6 Limited Biomarker [25]
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⏷ Show the Full List of 36 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Proline-rich acidic protein 1 (PRAP1). [26]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Proline-rich acidic protein 1 (PRAP1). [27]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proline-rich acidic protein 1 (PRAP1). [28]
Quercetin DM3NC4M Approved Quercetin increases the expression of Proline-rich acidic protein 1 (PRAP1). [29]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Proline-rich acidic protein 1 (PRAP1). [30]
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References

1 Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.Neoplasia. 2013 Feb;15(2):192-203. doi: 10.1593/neo.121334.
2 Urokinase gene transfer augments angiogenesis in ischemic skeletal and myocardial muscle.Mol Ther. 2007 Nov;15(11):1939-46. doi: 10.1038/sj.mt.6300262. Epub 2007 Jul 24.
3 Amiloride modulates urokinase gene expression at both transcription and post-transcription levels in human colon cancer cells.Clin Exp Metastasis. 1995 May;13(3):196-202. doi: 10.1007/BF00132208.
4 Regulation of the uPA gene in various grades of human glioma cells.Int J Oncol. 2001 Jan;18(1):71-9.
5 Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis: role of the uPA receptor and S100A8/A9 proteins.J Biol Chem. 2011 Jun 24;286(25):22665-77. doi: 10.1074/jbc.M110.202135. Epub 2011 May 2.
6 Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer.Biomaterials. 2018 Jan;152:47-62. doi: 10.1016/j.biomaterials.2017.10.035. Epub 2017 Oct 21.
7 Suppressive effects of a proton beam on tumor growth and lung metastasis through the inhibition of metastatic gene expression in 4T1 orthotopic breast cancer model.Int J Oncol. 2016 Jul;49(1):336-42. doi: 10.3892/ijo.2016.3520. Epub 2016 May 13.
8 Genetic polymorphism of the plasminogen activator inhibitor-1 is associated with an increased risk of endometrial cancer.J Surg Oncol. 2011 Dec;104(7):755-9. doi: 10.1002/jso.22035. Epub 2011 Jul 14.
9 Epidermal growth factor receptor-mediated regulation of urokinase plasminogen activator expression and glioblastoma invasion via C-SRC/MAPK/AP-1 signaling pathways.J Neuropathol Exp Neurol. 2010 Jun;69(6):582-92. doi: 10.1097/NEN.0b013e3181e008fe.
10 Proline-rich acidic protein 1 (PRAP1) is a novel interacting partner of MAD1 and has a suppressive role in mitotic checkpoint signalling in hepatocellular carcinoma.J Pathol. 2014 May;233(1):51-60. doi: 10.1002/path.4319. Epub 2014 Jan 27.
11 p53 and lung cancer.Pathol Biol (Paris). 1997 Dec;45(10):852-63.
12 Impact of expression of the uPA system in sarcomas.Biomark Med. 2013 Jun;7(3):473-80. doi: 10.2217/bmm.12.105.
13 Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - 1 (TGF-1) and potential effects on migration and invasion.BMC Cancer. 2017 May 19;17(1):350. doi: 10.1186/s12885-017-3349-7.
14 Characterization of spontaneous and TGF--induced cell motility of primary human normal and neoplastic mammary cells in vitro using novel real-time technology.PLoS One. 2013;8(2):e56591. doi: 10.1371/journal.pone.0056591. Epub 2013 Feb 14.
15 miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer.Mol Med Rep. 2014 Nov;10(5):2613-20. doi: 10.3892/mmr.2014.2558. Epub 2014 Sep 11.
16 Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer.World J Urol. 2020 Oct;38(10):2501-2511. doi: 10.1007/s00345-019-03038-5. Epub 2019 Dec 4.
17 Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation.Blood. 2009 Feb 12;113(7):1535-42. doi: 10.1182/blood-2008-08-172338. Epub 2008 Nov 24.
18 Regulation of the urokinase gene by the retinoblastoma protein.DNA Cell Biol. 1994 Nov;13(11):1063-9. doi: 10.1089/dna.1994.13.1063.
19 Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas.BMC Cancer. 2010 Apr 19;10:151. doi: 10.1186/1471-2407-10-151.
20 The expression of urokinase-related genes in superficial and invasive transitional cell carcinoma.Int J Oncol. 1998 Jan;12(1):175-80. doi: 10.3892/ijo.12.1.175.
21 Progression of Osteosarcoma from a Non-Metastatic to a Metastatic Phenotype Is Causally Associated with Activation of an Autocrine and Paracrine uPA Axis.PLoS One. 2015 Aug 28;10(8):e0133592. doi: 10.1371/journal.pone.0133592. eCollection 2015.
22 High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis.Am J Hematol. 2005 May;79(1):26-35. doi: 10.1002/ajh.20337.
23 Deflazacort modulates the fibrinolytic pattern and reduces uPA-dependent chemioinvasion and proliferation in rheumatoid arthritis synoviocytes.Rheumatology (Oxford). 2005 Oct;44(10):1255-62. doi: 10.1093/rheumatology/kei006. Epub 2005 Jul 5.
24 Up-regulation of urinary-type plasminogen activator correlates with high-risk papillary thyroid carcinoma with BRAF(V600E) mutation and its possible molecular mechanism.Pathol Res Pract. 2014 Nov;210(11):733-8. doi: 10.1016/j.prp.2014.06.025. Epub 2014 Jul 16.
25 Urokinase plasminogen activator, uPa receptor, and its inhibitor in vernal keratoconjunctivitis.Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1364-70. doi: 10.1167/iovs.04-1196.
26 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.
27 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
28 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
29 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
30 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.